Docetaxel Kabi

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ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 

DOCETAXEL KABI 20 mg/1 ml concentrate for solution for infusion 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each ml of concentrate contains 20 mg docetaxel anhydrous. 

 

One vial of 1 ml of concentrate contains 20 mg of docetaxel. 

 

Excipient with known effect 

Each vial of concentrate contains 0.5 ml of ethanol anhydrous (395 mg). 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Concentrate for solution for infusion (sterile concentrate). 

 

The concentrate is a clear, colourless to pale yellow solution. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 

 

Breast cancer 

 

DOCETAXEL KABI in combination with doxorubicin and cyclophosphamide is indicated for the 

adjuvant treatment of patients with: 

• operable node-positive breast cancer 

• operable node-negative breast cancer. 
 

For patients with operable node-negative breast cancer, adjuvant treatment should be restricted to 

patients eligible to receive chemotherapy according to internationally established criteria for primary 

therapy of early breast cancer (see section 5.1). 

 

DOCETAXEL KABI in combination with doxorubicin is indicated for the treatment of patients with 

locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for 

this condition. 

 

DOCETAXEL KABI monotherapy is indicated for the treatment of patients with locally advanced or 

metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have 

included an anthracycline or an alkylating agent. 

 

DOCETAXEL KABI in combination with trastuzumab is indicated for the treatment of patients with 

metastatic breast cancer whose tumours over express HER2 and who previously have not received 

chemotherapy for metastatic disease. 

 

DOCETAXEL KABI in combination with capecitabine is indicated for the treatment of patients with 

locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy 

should have included an anthracycline. 



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Non-small cell lung cancer 

 

DOCETAXEL KABI is indicated for the treatment of patients with locally advanced or metastatic 

non-small cell lung cancer after failure of prior chemotherapy. 

 

DOCETAXEL KABI in combination with cisplatin is indicated for the treatment of patients with 

unresectable, locally advanced or metastatic non-small cell lung cancer, in patients who have not 

previously received chemotherapy for this condition. 

 

Prostate cancer 

 

DOCETAXEL KABI in combination with prednisone or prednisolone is indicated for the treatment of 

patients with castration-resistant metastatic prostate cancer. 

 

DOCETAXEL KABI in combination with androgen-deprivation therapy (ADT), with or without 

prednisone or prednisolone, is indicated for the treatment of patients with metastatic hormone-

sensitive prostate cancer. 

 

Gastric adenocarcinoma 

 

DOCETAXEL KABI in combination with cisplatin and 5-fluorouracil is indicated for the treatment of 

patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal 

junction, who have not received prior chemotherapy for metastatic disease. 

 

Head and neck cancer 

 

DOCETAXEL KABI in combination with cisplatin and 5-fluorouracil is indicated for the induction 

treatment of patients with locally advanced squamous cell carcinoma of the head and neck. 

 

 

4.2 Posology and method of administration 

 

The use of docetaxel should be confined to units specialised in the administration of cytotoxic 

chemotherapy and it should only be administered under the supervision of a physician qualified in the 

use of anticancer chemotherapy (see section 6.6). 

 

Posology 

For breast, non-small cell lung, gastric, and head and neck cancers, premedication consisting of an oral 

corticosteroid, such as dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to 

docetaxel administration, unless contraindicated, can be used (see section 4.4).  

For metastatic castration-resistant prostate cancer, given the concurrent use of prednisone or 

prednisolone the recommended premedication regimen is oral dexamethasone 8 mg, 12 hours, 3 hours 

and 1 hour before the docetaxel infusion (see section 4.4). 

For metastatic hormone-sensitive prostate cancer, irrespective of the concurrent use of prednisone or 

prednisolone, the recommended premedication regimen is oral dexamethasone 8 mg 12 hours, 3 hours, 

and 1 hour before docetaxel infusion (see section 4.4). 

 

Prophylactic G-CSF may be used to mitigate the risk of haematological toxicities. 

 

Docetaxel is administered as a one-hour infusion every three weeks.  

 

Breast cancer 

In the adjuvant treatment of operable node-positive and node-negative breast cancer, the recommended 

dose of docetaxel is 75 mg/m2 administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 

500 mg/m2 every 3 weeks for 6 cycles (TAC regimen) (see also Dose adjustments during treatment). 

For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose 



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of docetaxel is 100 mg/m2 in monotherapy. In first-line treatment, docetaxel 75 mg/m2 is given in 

combination therapy with doxorubicin (50 mg/m2). 

 

In combination with trastuzumab the recommended dose of docetaxel is 100 mg/m2 every three weeks, 

with trastuzumab administered weekly. In the pivotal study the initial docetaxel infusion was started 

the day following the first dose of trastuzumab. The subsequent docetaxel doses were administered 

immediately after completion of the trastuzumab infusion, if the preceding dose of trastuzumab was 

well tolerated. For trastuzumab dose and administration, see trastuzumab summary of product 

characteristics.  

 

In combination with capecitabine, the recommended dose of docetaxel is 75 mg/m2 every three weeks, 

combined with capecitabine at 1250 mg/m2 twice daily (within 30 minutes after a meal) for 2 weeks 

followed by 1-week rest period. For capecitabine dose calculation according to body surface area, see 

capecitabine summary of product characteristics.  

 

Non-small cell lung cancer 

In chemotherapy naïve patients treated for non-small cell lung cancer, the recommended dose regimen 

is docetaxel 75 mg/m2 immediately followed by cisplatin 75 mg/m2 over 30-60 minutes. For treatment 

after failure of prior platinum-based chemotherapy, the recommended dose is 75 mg/m² as a single 

agent. 

 

Prostate cancer 

Prostate cancer Metastatic castration-resistant prostate cancer  
The recommended dose of docetaxel is 75 mg/m2. Prednisone or prednisolone 5 mg orally twice daily 

is administered continuously (see section 5.1). 

 

Metastatic hormone-sensitive prostate cancer 

The recommended dose of docetaxel is 75 mg/m2 every 3 weeks for 6 cycles. Prednisone or 

prednisolone 5 mg orally twice daily may be administered continuously. 

 

Gastric adenocarcinoma 

The recommended dose of docetaxel is 75 mg/m2 as a 1-hour infusion, followed by cisplatin 

75 mg/m2, as a 1- to 3- hour infusion (both on day 1 only), followed by 5-fluorouracil 750 mg/m2 per 

day given as a 24-hour continuous infusion for 5 days, starting at the end of the cisplatin infusion. 

Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and 

appropriate hydration for cisplatin administration. Prophylactic G-CSF should be used to mitigate the 

risk of haematological toxicities (see also Dose adjustments during treatment). 

 

Head and neck cancer 

Patients must receive premedication with antiemetics and appropriate hydration (prior to and after 

cisplatin administration). Prophylactic G-CSF may be used to mitigate the risk of haematological 

toxicities. All patients on the docetaxel-containing arm of the TAX 323 and TAX 324 studies, received 

prophylactic antibiotics. 

 

• Induction chemotherapy followed by radiotherapy (TAX 323) 
For the induction treatment of inoperable locally advanced squamous cell carcinoma of the head 

and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m2 as a 1 hour infusion 

followed by cisplatin 75 mg/m2 over 1 hour, on day one, followed by 5-fluorouracil as a 

continuous infusion at 750 mg/m2 per day for five days. This regimen is administered every 

3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy. 

 

• Induction chemotherapy followed by chemoradiotherapy (TAX 324) 
For the induction treatment of patients with locally advanced (technically unresectable, low 

probability of surgical cure, and aiming at organ preservation) squamous cell carcinoma of the 

head and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m2 as a 1 hour 

intravenous infusion on day 1, followed by cisplatin 100 mg/m2 administered as a 30-minute to 

3-hour infusion, followed by 5-fluorouracil 1000 mg/m2/day as a continuous infusion from day 1 



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to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, 

patients should receive chemoradiotherapy. 

 

For cisplatin and 5-fluorouracil dose modifications, see the corresponding summary of product 

characteristics. 

 

Dose adjustments during treatment 

 

General 

Docetaxel should be administered when the neutrophil count is ≥ 1,500 cells/mm3. 

In patients who experienced either febrile neutropenia, neutrophil count < 500 cells/mm3 for more than 

one week, severe or cumulative cutaneous reactions or severe peripheral neuropathy during docetaxel 

therapy, the dose of docetaxel should be reduced from 100 mg/m2 to 75 mg/m2 and/or from 75 to 

60 mg/m². If the patient continues to experience these reactions at 60 mg/m², the treatment should be 

discontinued. 

 

Adjuvant therapy for breast cancer 

Primary G-CSF prophylaxis should be considered in patients who receive docetaxel, doxorubicin and 

cyclophosphamide (TAC) adjuvant therapy for breast cancer. Patients who experience febrile 

neutropenia and/or neutropenic infection should have their docetaxel dose reduced to 60 mg/m² in all 

subsequent cycles (see sections 4.4 and 4.8). Patients who experience Grade 3 or 4 stomatitis should 

have their dose decreased to 60 mg/m². 

 

In combination with cisplatin 

For patients who are dosed initially at docetaxel 75 mg/m2 in combination with cisplatin and whose 

nadir of platelet count during the previous course of therapy is < 25,000 cells/mm3, or in patients who 

experience febrile neutropenia, or in patients with serious non-haematologic toxicities, the docetaxel 

dose in subsequent cycles should be reduced to 65 mg/m2. For cisplatin dose adjustments, see the 

corresponding summary of product characteristics.  

 

In combination with capecitabine 

• For capecitabine dose modifications, see capecitabine summary of product characteristics. 

• For patients developing the first appearance of Grade 2 toxicity, which persists at the time of the 
next docetaxel/capecitabine treatment, delay treatment until resolved to Grade 0-1, and resume at 

100% of the original dose. 

• For patients developing the second appearance of Grade 2 toxicity, or the first appearance of 
Grade 3 toxicity, at any time during the treatment cycle, delay treatment until resolved to Grade 

0-1 and then resume treatment with docetaxel 55 mg/m². 

• For any subsequent appearances of toxicities, or any Grade 4 toxicities, discontinue the docetaxel 
dose. 

 

For trastuzumab dose modifications, see trastuzumab summary of product characteristics. 

 

In combination with cisplatin and 5-fluorouracil 

If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite 

G-CSF use, the docetaxel dose should be reduced from 75 to 60 mg/m2. If subsequent episodes of 

complicated neutropenia occur the docetaxel dose should be reduced from 60 to 45 mg/m2. In case of 

Grade 4 thrombocytopenia the docetaxel dose should be reduced from 75 to 60 mg/m2. Patients should 

not be retreated with subsequent cycles of docetaxel until neutrophils recover to a level 

>1,500 cells/mm3 and platelets recover to a level >100,000 cells/mm3. Discontinue treatment if these 

toxicities persist (see section 4.4). 

Recommended dose modifications for toxicities in patients treated with docetaxel in combination with 

cisplatin and 5-fluorouracil (5-FU): 

 

 

 



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Toxicity Dose adjustment 

Diarrhoea grade 3  First episode: reduce 5-FU dose by 20%. 

Second episode: then reduce docetaxel dose by 20%. 

Diarrhoea grade 4 First episode: reduce docetaxel and 5-FU doses by 20%. 

Second episode: discontinue treatment. 

Stomatitis/mucositis grade 3  First episode: reduce 5-FU dose by 20%. 

Second episode: stop 5-FU only, at all subsequent cycles. 

Third episode: reduce docetaxel dose by 20%. 

Stomatitis/mucositis grade 4 First episode: stop 5-FU only, at all subsequent cycles. 

Second episode: reduce docetaxel dose by 20%. 

 

For cisplatin and 5-fluorouracil dose adjustments, see the corresponding summary of product 

characteristics. 

 

In the pivotal SCCHN studies patients who experienced complicated neutropenia (including prolonged 

neutropenia, febrile neutropenia, or infection), it was recommended to use G-CSF to provide 

prophylactic coverage (eg, day 6-15) in all subsequent cycles. 

 

Special populations 

 

Patients with hepatic impairment 

Based on pharmacokinetic data with docetaxel at 100 mg/m² as single agent, patients who have both 

elevations of transaminase (ALT and/or AST) greater than 1.5 times the upper limit of the normal 

range (ULN) and alkaline phosphatase greater than 2.5 times the ULN, the recommended dose of 

docetaxel is 75 mg/m2 (see sections 4.4 and 5.2). For those patients with serum bilirubin > ULN and/or 

ALT and AST > 3.5 times the ULN associated with alkaline phosphatase > 6 times the ULN, no 

dose-reduction can be recommended and docetaxel should not be used unless strictly indicated. 

In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric 

adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST > 1.5 × ULN 

associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no 

dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No 

data are available in patients with hepatic impairment treated by docetaxel in combination in the other 

indications.  

 

Paediatric population 

The safety and efficacy of DOCETAXEL KABI in nasopharyngeal carcinoma in children aged 

1 month to less than 18 years have not yet been established. 

There is no relevant use of DOCETAXEL KABI in the paediatric population in the indications breast 

cancer, non-small cell lung cancer, prostate cancer, gastric carcinoma and head and neck cancer, not 

including type II and III less differentiated nasopharyngeal carcinoma. 

 

Elderly 

Based on a population pharmacokinetic analysis, there are no special instructions for use in the elderly. 

In combination with capecitabine, for patients 60 years of age or more, a starting dose reduction of 

capecitabine to 75% is recommended (see capecitabine summary of product characteristics). 

 

Method of administration 

For instructions on preparation and administration of the product, see section 6.6. 

 

 

4.3 Contraindications 

 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 



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Patients with baseline neutrophil count of < 1,500 cells/mm3. 

 

Patients with severe liver impairment (see sections 4.2 and 4.4). 

 

Contraindications for other medicinal products also apply, when combined with docetaxel. 

 

 

4.4 Special warnings and precautions for use 

 

For breast and non-small cell lung cancers, premedication consisting of an oral corticosteroid, such as 

dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to docetaxel 

administration, unless contraindicated, can reduce the incidence and severity of fluid retention as well 

as the severity of hypersensitivity reactions. For prostate cancer, the premedication is oral 

dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the docetaxel infusion (see section 4.2). 

 

Haematology 

 

Neutropenia is the most frequent adverse reaction of docetaxel. Neutrophil nadirs occurred at a median 

of 7 days but this interval may be shorter in heavily pre-treated patients. Frequent monitoring of 

complete blood counts should be conducted on all patients receiving docetaxel. Patients should be 

retreated with docetaxel when neutrophils recover to a level ≥ 1,500 cells/mm3 (see section 4.2). 

 

In the case of severe neutropenia (< 500 cells/mm3 for seven days or more) during a course of 

docetaxel therapy, a reduction in dose for subsequent courses of therapy or the use of appropriate 

symptomatic measures are recommended (see section 4.2). 

 

In patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (TCF), febrile 

neutropenia and neutropenic infection occurred at lower rates when patients received prophylactic 

G-CSF. Patients treated with TCF should receive prophylactic G-CSF to mitigate the risk of 

complicated neutropenia (febrile neutropenia, prolonged neutropenia or neutropenic infection). 

Patients receiving TCF should be closely monitored (see sections 4.2 and 4.8). 

 

In patients treated with docetaxel in combination with doxorubicin and cyclophosphamide (TAC), 

febrile neutropenia and/or neutropenic infection occurred at lower rates when patients received 

primary G-CSF prophylaxis. Primary G-CSF prophylaxis should be considered in patients who receive 

adjuvant therapy with TAC for breast cancer to mitigate the risk of complicated neutropenia (febrile 

neutropenia, prolonged neutropenia or neutropenic infection). Patients receiving TAC should be 

closely monitored (see sections 4.2 and 4.8). 

 

Gastrointestinal reactions 

 

Caution is recommended for patients with neutropenia, particularly at risk for developing 

gastrointestinal complications. Although majority of cases occurred during the first or second cycle of 

docetaxel containing regimen, enterocolitis could develop at any time, and could lead to death as early 

as on the first day of onset. Patients should be closely monitored for early manifestations of serious 

gastrointestinal toxicity (see sections 4.2, 4.4 Haematology, and 4.8). 

 

Hypersensitivity reactions 

 

Patients should be observed closely for hypersensitivity reactions especially during the first and 

second infusions. Hypersensitivity reactions may occur within a few minutes following the initiation 

of the infusion of docetaxel, thus facilities for the treatment of hypotension and bronchospasm should 

be available. If hypersensitivity reactions occur, minor symptoms such as flushing or localised 

cutaneous reactions do not require interruption of therapy. However, severe reactions, such as severe 

hypotension, bronchospasm or generalised rash/erythema require immediate discontinuation of 

docetaxel and appropriate therapy. Patients who have developed severe hypersensitivity reactions 

should not be re-challenged with docetaxel. Patients who have previously experienced a 



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hypersensitivity reaction to paclitaxel may be at risk to develop hypersensitivity reaction to docetaxel, 

including more severe hypersensitivity reaction. These patients should be closely monitored during 

initiation of docetaxel therapy. 

 

Cutaneous reactions 

 

Localised skin erythema of the extremities (palms of the hands and soles of the feet) with oedema 

followed by desquamation has been observed. Severe symptoms such as eruptions followed by 

desquamation which lead to interruption or discontinuation of docetaxel treatment were reported (see 

section 4.2). 

 

Severe Cutaneous Adverse Reactions (SCARs) such as Stevens-Johnson Syndrome (SJS), Toxic 

Epidermal Necrolysis (TEN) and Acute Generalized Exanthematous Pustulosis (AGEP) have been 

reported with docetaxel treatment. Patients should be informed about the signs and symptoms of 

serious skin manifestations and closely monitored. If signs and symptoms suggestive of these reactions 

appear discontinuation of docetaxel should be considered. 

 

Fluid retention 

 

Patients with severe fluid retention such as pleural effusion, pericardial effusion and ascites should be 

monitored closely. 

 

Respiratory disorders 

 

Acute respiratory distress syndrome, interstitial pneumonia/pneumonitis, interstitial lung disease, 

pulmonary fibrosis and respiratory failure have been reported and may be associated with fatal 

outcome. Cases of radiation pneumonitis have been reported in patients receiving concomitant 

radiotherapy. 

 

If new or worsening pulmonary symptoms develop, patients should be closely monitored, promptly 

investigated, and appropriately treated. Interruption of docetaxel therapy is recommended until 

diagnosis is available. Early use of supportive care measures may help improve the condition. The 

benefit of resuming docetaxel treatment must be carefully evaluated. 

 

Patients with liver impairment 

 

In patients treated with docetaxel at 100 mg/m2 as single agent who have serum transaminase levels 

(ALT and/or AST) greater than 1.5 times the ULN concurrent with serum alkaline phosphatase levels 

greater than 2.5 times the ULN, there is a higher risk of developing severe adverse reactions such as 

toxic deaths including sepsis and gastrointestinal haemorrhage which can be fatal, febrile neutropenia, 

infections, thrombocytopenia, stomatitis and asthenia. Therefore, the recommended dose of docetaxel 

in those patients with elevated liver function test (LFTs) is 75 mg/m2 and LFTs should be measured at 

baseline and before each cycle (see section 4.2). 

For patients with serum bilirubin levels > ULN and/or ALT and AST > 3.5 times the ULN concurrent 

with serum alkaline phosphatase levels > 6 times the ULN, no dose-reduction can be recommended 

and docetaxel should not be used unless strictly indicated. 

In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric 

adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST > 1.5 × ULN 

associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no 

dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No 

data are available in patients with hepatic impairment treated by docetaxel in combination in the other 

indications.  

 

Patients with renal impairment 

 

There are no data available in patients with severely impaired renal function treated with docetaxel. 

 



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Nervous system 

 

The development of severe peripheral neurotoxicity requires a reduction of dose (see section 4.2). 

 

Cardiac toxicity 

 

Heart failure has been observed in patients receiving docetaxel in combination with trastuzumab, 

particularly following anthracycline (doxorubicin or epirubicin)-containing chemotherapy. This may 

be moderate to severe and has been associated with death (see section 4.8). 

 

When patients are candidates for treatment with docetaxel in combination with trastuzumab, they 

should undergo baseline cardiac assessment. Cardiac function should be further monitored during 

treatment (e.g. every three months) to help identify patients who may develop cardiac dysfunction. For 

more details see summary of product characteristics of trastuzumab.  

 

Ventricular arrhythmia including ventricular tachycardia (sometimes fatal) has been reported in 

patients treated with docetaxel in combination regimens including doxorubicin, 5-fluorouracil and/ or 

cyclophosphamide (see section 4.8).  

Baseline cardiac assessment is recommended.   

 

Eye disorders 

 

Cystoid macular oedema (CMO) has been reported in patients treated with docetaxel. Patients with 

impaired vision should undergo a prompt and complete ophthalmologic examination. In case CMO is 

diagnosed, docetaxel treatment should be discontinued and appropriate treatment initiated (see section 

4.8). 

 

Second primary malignancies 

Second primary malignancies have been reported when docetaxel was given in combination with 

anticancer treatments known to be associated with second primary malignancies.  Second primary 

malignancies (including acute myeloid leukemia, myelodysplastic syndrome and non-Hodgkin 

lymphoma) may occur several months or years after docetaxel-containing therapy. Patients should be 

monitored for second primary malignancies (see section 4.8). 

 

Others 

 

Contraceptive measures must be taken by both men and women during treatment and for men at least 

6 months after cessation of therapy (see section 4.6). 

 

The concomitant use of docetaxel with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, 

clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and 

voriconazole) should be avoided (see section 4.5). 

 

Additional cautions for use in adjuvant treatment of breast cancer 

 

Complicated neutropenia 

For patients who experience complicated neutropenia (prolonged neutropenia, febrile neutropenia or 

infection), G-CSF and dose reduction should be considered (see section 4.2). 

 

Gastrointestinal reactions 

Symptoms such as early abdominal pain and tenderness, fever, diarrhoea, with or without neutropenia, 

may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated 

promptly. 

 

 

 

 



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Congestive heart failure (CHF) 

Patients should be monitored for symptoms of congestive heart failure during therapy and during the 

follow up period. In patients treated with the TAC regimen for node positive breast cancer, the risk of 

CHF has been shown to be higher during the first year after treatment (see sections 4.8 and 5.1). 

 

Patients with 4+ nodes 

As the benefit observed in patient with 4+ nodes was not statistically significant on disease-free 

survival (DFS) and overall survival (OS), the positive benefit/risk ratio for TAC in patients with 4+ 

nodes was not fully demonstrated at the final analysis (see section 5.1). 

 

Elderly 

Cautions for use in adjuvant treatment of breast cancer 

There are limited data available in patients > 70 years of age on docetaxel use in combination with 

doxorubicin and cyclophosphamide. 

 

Cautions for use in castration-resistant prostate cancer 

Of the 333 patients treated with docetaxel every three weeks in a prostate cancer study, 209 patients 

were 65 years of age or greater and 68 patients were older than 75 years. In patients treated with 

docetaxel every three weeks, the incidence of related nail changes occurred at a rate ≥ 10% higher in 

patients who were 65 years of age or greater compared to younger patients. The incidence of related 

fever, diarrhoea, anorexia, and peripheral oedema occurred at rates ≥ 10% higher in patients who were 

75 years of age or greater versus less than 65 years. 

 

Cautions for use in hormone-sensitive prostate cancer 

Of the 545 patients treated with docetaxel every 3 weeks in a hormone-sensitive prostate cancer study 

(STAMPEDE), 296 patients were 65 years of age or older, and 48 patients were 75 years of age or 

older. More patients aged ≥65 years in the docetaxel arm reported hypersensitivity reaction, 

neutropenia, anaemia, fluid retention, dyspnea, and nail changes when compared to the patients aged 

less than 65 years. None of these increases in frequency reached 10% difference with the control arm. 

In patients who were 75 years of age or older, when compared to younger patients, neutropenia, 

anaemia, diarrhea, dyspnea and upper respiratory tract infection were reported with a greater incidence 

(at least 10% higher).  

 

Cautions for use in gastric adenocarcinoma cancer 

Among the 300 (221 patients in the phase III part of the study and 79 patients in the phase II part) 

patients treated with docetaxel in combination with cisplatin and 5-fluorouracil in the gastric cancer 

study, 74 were 65 years of age or older and 4 patients were 75 years of age or older. The incidence of 

serious adverse events was higher in older people compared to younger patients. The incidence of the 

following adverse events (all grades): lethargy, stomatitis, neutropenic infection occurred at rates 

≥ 10% higher in patients who were 65 years of age or older compared to younger patients. 

Elderly treated with TCF should be closely monitored. 

 

Excipients 

 
This medicinal product contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 395 mg ethanol 

anhydrous per vial, equivalent to 10 ml of beer or 4 ml wine. 

Harmful for those suffering from alcoholism. 

To be taken into account in pregnant or breast-feeding women, children and high-risk groups 

such as patients with liver disease, or epilepsy. 
 

Consideration should be given to possible effects on the central nervous system. 

 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

The amount of alcohol in this medicinal product may alter the effects of other medicinal products. 



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In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant 

administration of compounds which induce, inhibit or are metabolised by (and thus may inhibit the 

enzyme competitively) cytochrome P450-3A such as ciclosporine, ketoconazole and erythromycin. As 

a result, caution should be exercised when treating patients with these medicinal products as 

concomitant therapy since there is a potential for a significant interaction. 

In case of combination with CYP3A4 inhibitors, the occurrence of docetaxel adverse reactions may 

increase, as a result of reduced metabolism. If the concomitant use of a strong CYP3A4 inhibitor (e.g., 

ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, 

telithromycin and voriconazole) cannot be avoided, a close clinical surveillance is warranted and a 

dose-adjustment of docetaxel may be suitable during the treatment with the strong CYP3A4 inhibitor 

(see section 4.4). In a pharmacokinetic study with 7 patients, the co-administration of docetaxel with 

the strong CYP3A4 inhibitor ketoconazole leads to a significant decrease in docetaxel clearance by 

49%. 

Docetaxel pharmacokinetics in the presence of prednisone was studied in patients with metastatic 

prostate cancer. Docetaxel is metabolised by CYP3A4 and prednisone is known to induce CYP3A4. 

No statistically significant effect of prednisone on the pharmacokinetics of docetaxel was observed. 

 

Docetaxel is highly protein bound (> 95%). Although the possible in vivo interaction of docetaxel with 

concomitantly administered medicinal product has not been investigated formally, in vitro interactions 

with tightly protein-bound agents such as erythromycin, diphenhydramine, propranolol, propafenone, 

phenytoin, salicylate, sulfamethoxazole and sodium valproate did not affect protein binding of 

docetaxel. In addition, dexamethasone did not affect protein binding of docetaxel. Docetaxel did not 

influence the binding of digitoxin. 

 

The pharmacokinetics of docetaxel, doxorubicin and cyclophosphamide were not influenced by their 

co-administration. Limited data from a single uncontrolled study were suggestive of an interaction 

between docetaxel and carboplatin. When combined to docetaxel, the clearance of carboplatin was 

about 50% higher than values previously reported for carboplatin monotherapy. 

 

 

4.6 Fertility, pregnancy and lactation 

 

Women of childbearing potential/ Contraception in males and females 

 

Women of childbearing age receiving docetaxel should be advised to avoid becoming pregnant, and to 

inform the treating physician immediately should this occur. An effective method of contraception 

should be used during treatment. 

 

Pregnancy 

 

There is no information on the use of docetaxel in pregnant women. Docetaxel has been shown to be 

both embryotoxic and foetotoxic in rabbits and rats, and to reduce fertility in rats (see section 5.3). As 

with other cytotoxic medicinal products, docetaxel may cause foetal harm when administered to 

pregnant women. Therefore, docetaxel must not be used during pregnancy unless clearly indicated.  

 

Breast-feeding 

 

Docetaxel is a lipophilic substance but it is not known whether it is excreted in human milk. 

Consequently, because of the potential for adverse reactions in nursing infants, breast feeding must be 

discontinued for the duration of docetaxel therapy. 

 

 

 



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Fertility 

 

In non clinical studies, docetaxel has genotoxic effects and may alter male fertility (see section 5.3). 

Therefore, men being treated with docetaxel are advised not to father a child during and up to 

6 months after treatment and to seek advice on conservation of sperm prior to treatment. 

 

 

4.7 Effects on ability to drive and use machines 

 

No studies on the effects on the ability to drive and use machines have been performed. The amount of 

alcohol in this medicinal product and the side effects of the product may impair the ability to drive or 

use machines (see sections 4.4 and 4.8). Therefore, patients should be warned of the potential impact 

of the amount of alcohol and the side effects of this medicinal product on the ability to drive or use 

machines, and be advised not to drive or use machines if they experience these side effects during 

treatment. 

 

 

4.8 Undesirable effects 

 

Summary of the safety profile for all indications 

 

The adverse reactions considered to be possibly or probably related to the administration of docetaxel 

have been obtained in: 

 

• 1,312 and 121 patients who received 100 mg/m² and 75 mg/m² of docetaxel as a single agent 
respectively. 

• 258 patients who received docetaxel in combination with doxorubicin. 

• 406 patients who received docetaxel in combination with cisplatin. 

• 92 patients treated with docetaxel in combination with trastuzumab. 

• 255 patients who received docetaxel in combination with capecitabine. 

• 332 patients (TAX327) who received docetaxel in combination with prednisone or prednisolone 
(clinically important treatment related adverse events are presented). 

• 1,276 patients (744 and 532 in TAX 316 and GEICAM 9805 respectively) who received 
docetaxel in combination with doxorubicin and cyclophosphamide (clinically important 

treatment related adverse events are presented). 

• 300 gastric adenocarcinoma patients (221 patients in the phase III part of the study and 
79 patients in the phase II part) who received docetaxel in combination with cisplatin and 

5-fluorouracil (clinically important treatment related adverse events are presented). 

• 174 and 251 head and neck cancer patients who received docetaxel in combination with 
cisplatin and 5-fluorouracil (clinically important treatment related adverse events are presented). 

• 545 patients (STAMPEDE study) who received docetaxel in combination with prednisone or 
prednisolone and ADT. 

 

These reactions were described using the NCI Common Toxicity Criteria (grade 3 = G3; 

grade 3-4 = G3/4; grade 4 = G4), the COSTART and the MedDRA terms. Frequencies are defined as: 
very common (≥ 1/10), common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare 

(≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from available 

data). 

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 

 

The most commonly reported adverse reactions of docetaxel alone are: neutropenia (which was 

reversible and not cumulative; the median day to nadir was 7 days and the median duration of severe 

neutropenia (< 500 cells/mm3) was 7 days), anaemia, alopecia, nausea, vomiting, stomatitis, diarrhoea 

and asthenia. The severity of adverse events of docetaxel may be increased when docetaxel is given in 

combination with other chemotherapeutic agents. 

 



13 

For combination with trastuzumab, adverse events (all grades) reported in ≥ 10% are displayed. There 

was an increased incidence of SAEs (40% vs. 31%) and Grade 4 AEs (34% vs. 23%) in the 

trastuzumab combination arm compared to docetaxel monotherapy. 

 

For combination with capecitabine, the most frequent treatment-related undesirable effects (≥ 5%) 

reported in a phase III study in breast cancer patients failing anthracycline treatment are presented (see 

capecitabine summary of product characteristics). 

 

For combination with ADT and with prednisone or prednisolone (STAMPEDE study), adverse events 

occurring occurring over the 6 cycles of treatment with docetaxel and having at least 2% higher 

incidence in the docetaxel treatment arm by comparison to the control arm, are presented, using the 

CTCAE grading scale. 

 

The following adverse reactions are frequently observed with docetaxel:  

Immune system disorders 

 

Hypersensitivity reactions have generally occurred within a few minutes following the start of the 

infusion of docetaxel and were usually mild to moderate. The most frequently reported symptoms 

were flushing, rash with or without pruritus, chest tightness, back pain, dyspnoea and fever or chills. 

Severe reactions were characterised by hypotension and/or bronchospasm or generalized 

rash/erythema (see section 4.4). 

 

Nervous system disorders 

 

The development of severe peripheral neurotoxicity requires a reduction of dose (see sections 4.2 and 

4.4). Mild to moderate neuro-sensory signs are characterised by paraesthesia, dysesthesia or pain 

including burning. Neuro-motor events are mainly characterised by weakness. 

 

Skin and subcutaneous tissue disorders 

 

Reversible cutaneous reactions have been observed and were generally considered as mild to 

moderate. Reactions were characterised by a rash including localised eruptions mainly on the feet and 

hands (including severe hand and foot syndrome), but also on the arms, face or thorax, and frequently 

associated with pruritus. Eruptions generally occurred within one week after the docetaxel infusion. 

Less frequently, severe symptoms such as eruptions followed by desquamation which rarely lead to 

interruption or discontinuation of docetaxel treatment were reported (see sections 4.2 and 4.4). Severe 

nail disorders are characterised by hypo- or hyperpigmentation and sometimes pain and onycholysis. 

 

General disorders and administration site conditions 

 

Infusion site reactions were generally mild and consisted of hyper pigmentation, inflammation, 

redness or dryness of the skin, phlebitis or extravasation and swelling of the vein.  

Fluid retention includes events such as peripheral oedema and less frequently pleural effusion, 

pericardial effusion, ascites and weight gain. The peripheral oedema usually starts at the lower 

extremities and may become generalised with a weight gain of 3 kg or more. Fluid retention is 

cumulative in incidence and severity (see section 4.4). 

 

Tabulated list of adverse reactions in breast cancer for DOCETAXEL KABI 100 mg/m² single agent 

 

MedDRA system 

organ classes 

Very common 

adverse reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infections 

(G3/4: 5.7%; including 

sepsis and pneumonia, 

fatal in 1.7%) 

Infection associated 

with G4 neutropenia 

(G3/4: 4.6%) 

  



14 

MedDRA system 

organ classes 

Very common 

adverse reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Blood and lymphatic 

system disorders 

Neutropenia 

(G4: 76.4%); 

Anaemia 

(G3/4: 8.9%); 

Febrile neutropenia 

Thrombocytopenia 

(G4: 0.2%) 

  

Immune system 

disorders 

Hypersensitivity 

(G3/4: 5.3%) 

    

Metabolism and 

nutrition disorders 

Anorexia     

Nervous system 

disorders 

Peripheral sensory 

neuropathy 

(G3: 4.1%); 

Peripheral motor 

neuropathy 

(G3/4: 4%); 

Dysgeusia 

(severe: 0.07%) 

    

Cardiac disorders   Arrhythmia 

(G3/4: 0.7%) 

Cardiac failure 

Vascular disorders   Hypotension; 

Hypertension; 

Haemorrhage 

  

Respiratory, thoracic 

and mediastinal 

disorders 

Dyspnoea 

(severe: 2.7%) 

    

Gastrointestinal 

disorders 

Stomatitis 

(G3/4: 5.3%); 

Diarrhoea (G3/4: 4%); 

Nausea (G3/4: 4%); 

Vomiting (G3/4: 3%) 

Constipation 

(severe: 0.2%); 

Abdominal pain 

(severe: 1%); 

Gastrointestinal 

haemorrhage 

(severe: 0.3%) 

Oesophagitis 

(severe: 0.4%) 

Skin and subcutaneous 

tissue disorders 

Alopecia; 

Skin reaction 

(G3/4: 5.9%); 

Nail disorders 

(severe: 2.6%) 

    

Musculoskeletal and 

connective tissue 

disorders 

Myalgia 

(severe: 1.4%) 

Arthralgia   

General disorders and 

administration site 

conditions 

Fluid retention 

(severe: 6.5%); 

Asthenia 

(severe: 11.2%); 

Pain 

Infusion site reaction;  

Non-cardiac chest pain 

(severe: 0.4%) 

  

Investigations   G3/4 Blood bilirubin 

increased (< 5%); 

G3/4 Blood alkaline 

  



15 

MedDRA system 

organ classes 

Very common 

adverse reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

phosphatase increased 

(< 4%);G3/4 AST 

increased (< 3%); 

G3/4 ALT increased 

(< 2%) 

 

Description of selected adverse reactions in breast cancer for DOCETAXEL KABI 100 mg/m² single 

agent 

 

Blood and lymphatic system disorders 

Rare: bleeding episodes associated with grade 3/4 thrombocytopenia.  

 

Nervous system disorders 

Reversibility data are available among 35.3% of patients who developed neurotoxicity following 

docetaxel treatment at 100 mg/m² as single agent. The events were spontaneously reversible within 

3 months. 

 

Skin and subcutaneous tissue disorders 

Very rare: one case of alopecia non-reversible at the end of the study. 73% of the cutaneous reactions 

were reversible within 21 days. 

 

General disorders and administration site conditions 

The median cumulative dose to treatment discontinuation was more than 1,000 mg/m2 and the median 

time to fluid retention reversibility was 16.4 weeks (range 0 to 42 weeks). The onset of moderate and 

severe retention is delayed (median cumulative dose: 818.9 mg/m2) in patients with premedication 

compared with patients without premedication (median cumulative dose: 489.7 mg/m2); however, it 

has been reported in some patients during the early courses of therapy. 

 

Tabulated list of adverse reactions in non-small lung cancer for DOCETAXEL KABI 75 mg/m² single 

agent 

 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Infections and infestations Infections (G3/4: 5%)   

Blood and lymphatic system 

disorders 

Neutropenia (G4: 54.2%); 

Anaemia (G3/4: 10.8%); 

Thrombocytopenia (G4: 1.7%) 

Febrile neutropenia 

Immune system disorders   Hypersensitivity (no severe) 

Metabolism and nutrition 

disorders 

Anorexia   

Nervous system disorders Peripheral sensory neuropathy 

(G3/4: 0.8%) 

Peripheral motor neuropathy 

(G3/4: 2.5%) 

Cardiac disorders   Arrhythmia (no severe) 

Vascular disorders   Hypotension 

Gastrointestinal disorders Nausea (G3/4: 3.3%); 

Stomatitis (G3/4: 1.7%); 

Vomiting (G3/4: 0.8%); 

Diarrhoea (G3/4: 1.7%) 

Constipation 



16 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Skin and subcutaneous tissue 

disorders 

Alopecia; 

Skin reaction (G3/4: 0.8%) 

Nail disorders (severe: 0.8%) 

Musculoskeletal and 

connective tissue disorders 

  Myalgia 

General disorders and 

administration site conditions 

Asthenia (severe: 12.4%); 

Fluid retention 

(severe: 0.8%);Pain 

  

Investigations   G3/4 Blood bilirubin 

increased (< 2%) 

 

Tabulated list of adverse reactions in breast cancer for DOCETAXEL KABI 75 mg/m² in combination 

with doxorubicin 

 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 7.8%)     

Blood and lymphatic 

system disorders 

Neutropenia 

(G4: 91.7%); 

Anaemia (G3/4: 9.4%); 

Febrile neutropenia; 

Thrombocytopenia 

(G4: 0.8%) 

    

Immune system 

disorders 

  Hypersensitivity 

(G3/4: 1.2%) 

  

Metabolism and 

nutrition disorders 

  Anorexia   

Nervous system 

disorders 

Peripheral sensory 

neuropathy (G3: 0.4%) 

Peripheral motor 

neuropathy 

(G3/4: 0.4%) 

  

Cardiac disorders   Cardiac failure; 

Arrhythmia (no 

severe) 

  

Vascular disorders     Hypotension 

Gastrointestinal 

disorders 

Nausea (G3/4: 5%); 

Stomatitis 

(G3/4: 7.8%); 

Diarrhoea 

(G3/4: 6.2%); 

Vomiting (G3/4: 5%); 

Constipation 

    

Skin and subcutaneous 

tissue disorders 

Alopecia; 

Nail disorders 

(severe: 0.4%); 

Skin reaction (no 

severe) 

    



17 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Musculoskeletal and 

connective tissue 

disorders 

  Myalgia   

General disorders and 

administration site 

conditions 

Asthenia 

(severe: 8.1%); 

Fluid retention 

(severe: 1.2%); 

Pain 

Infusion site reaction   

Investigations   G3/4 Blood bilirubin 

increased (< 2.5%); 

G3/4 Blood alkaline 

phosphatase increased 

(< 2.5%) 

G3/4 AST increased 

(< 1%); 

G3/4 ALT increased 

(< 1%) 

 

Tabulated list of adverse reactions in non-small lung cancer for DOCETAXEL KABI 75 mg/m² in 

combination with cisplatin 

 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 5.7%)     

Blood and 

lymphatic system 

disorders 

Neutropenia (G4: 51.5%); 

Anaemia (G3/4: 6.9%); 

Thrombocytopenia 

(G4: 0.5%) 

Febrile neutropenia   

Immune system 

disorders 

Hypersensitivity 

(G3/4: 2.5%) 

    

Metabolism and 

nutrition disorders 

Anorexia     

Nervous system 

disorders 

Peripheral sensory 

neuropathy (G3: 3.7%); 

Peripheral motor 

neuropathy (G3/4: 2%) 

    

Cardiac disorders   Arrhythmia 

(G3/4: 0.7%) 

Cardiac failure 

Vascular disorders   Hypotension 

(G3/4: 0.7%) 

  

Gastrointestinal 

disorders 

Nausea (G3/4: 9.6%); 

Vomiting (G3/4: 7.6%); 

Diarrhoea (G3/4: 6.4%); 

Stomatitis (G3/4: 2%) 

Constipation   

Skin and 

subcutaneous 

tissue disorders 

Alopecia; 

Nail disorders 

(severe: 0.7%); 

Skin reaction (G3/4: 0.2%) 

    

Musculoskeletal 

and connective 

Myalgia (severe: 0.5%)     



18 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

tissue disorders 

General disorders 

and administration 

site conditions 

Asthenia (severe: 9.9%); 

Fluid retention 

(severe: 0.7%); 

Fever (G3/4: 1.2%) 

Infusion site reaction; 

Pain 

  

Investigations   G3/4 Blood bilirubin 

increased (2.1%); G3/4 

ALT increased (1.3%) 

G3/4 AST increased 

(0.5%); G3/4 Blood 

alkaline phosphatase 

increased (0.3%) 

 

Tabulated list of adverse reactions in breast cancer for DOCETAXEL KABI 100 mg/m² in 

combination with trastuzumab 

 

MedDRA system 

organ classes 

Very common adverse reactions Common adverse reactions 

 

Blood and lymphatic 

system disorders 

Neutropenia (G3/4: 32%); 

Febrile neutropenia (includes 

neutropenia associated with fever and 

antibiotic use) or neutropenic sepsis  

  

Metabolism and 

nutrition disorders 

Anorexia   

Psychiatric disorders Insomnia   

Nervous system 

disorders 

Paraesthesia; Headache; Dysgeusia; 

Hypoaesthesia 

  

Eye disorders Lacrimation increased; Conjunctivitis   

Cardiac disorders   Cardiac failure 

Vascular disorders Lymphoedema   

Respiratory, thoracic 

and mediastinal 

disorders 

Epistaxis; Pharyngolaryngeal pain; 

Nasopharyngitis; Dyspnoea; 

Cough; Rhinorrhoea 

  

Gastrointestinal 

disorders 

Nausea; Diarrhoea; Vomiting; 

Constipation; Stomatitis; Dyspepsia; 

Abdominal pain 

  

Skin and 

subcutaneous tissue 

disorders 

Alopecia; Erythema; Rash; Nail 

disorders 

  

Musculoskeletal and 

connective tissue 

disorders 

Myalgia; Arthralgia; Pain in 

extremity; Bone pain; Back pain 

  

General disorders 

and administration 

site conditions 

Asthenia; Oedema peripheral; 

Pyrexia; Fatigue; Mucosal 

inflammation; Pain; Influenza like 

illness; Chest pain; Chills 

Lethargy 

Investigations Weight increased   

 



19 

Description of selected adverse reactions in breast cancer for DOCETAXEL KABI 100 mg/m² in 

combination with trastuzumab 

 

Cardiac disorders 

Symptomatic cardiac failure was reported in 2.2% of the patients who received docetaxel plus 

trastuzumab compared to 0% of patients given docetaxel alone. In the docetaxel plus trastuzumab arm, 

64% had received a prior anthracycline as adjuvant therapy compared with 55% in the docetaxel arm 

alone. 

 

Blood and lymphatic system disorders 

Very common: Haematological toxicity was increased in patients receiving trastuzumab and 

docetaxel, compared with docetaxel alone (32% grade 3/4 neutropenia versus 22%, using 

NCI-CTC criteria). Note that this is likely to be an underestimate since docetaxel alone at a 

dose of 100 mg/m2 is known to result in neutropenia in 97% of patients, 76% grade 4, based 

on nadir blood counts. The incidence of febrile neutropenia/neutropenic sepsis was also 

increased in patients treated with Herceptin plus docetaxel (23% versus 17% for patients 

treated with docetaxel alone). 
 

Tabulated list of adverse reactions in breast cancer for DOCETAXEL KABI 75 mg/m² in combination 

with capecitabine 

 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Infections and infestations   Oral candidiasis (G3/4: < 1%) 

Blood and lymphatic system 

disorders 

Neutropenia (G3/4: 63%); 

Anaemia (G3/4: 10%) 

Thrombocytopenia (G3/4: 3%) 

Metabolism and nutrition 

disorders 

Anorexia (G3/4: 1%); 

Decreased appetite 

Dehydration (G3/4: 2%) 

Nervous system disorders Dysgeusia (G3/4: < 1%); 

Paraesthesia (G3/4: < 1%) 

 

Dizziness; 

Headache (G3/4: < 1%); 

Neuropathy peripheral 

Eye disorders Lacrimation increased   

Respiratory, thoracic and 

mediastinal disorders 

Pharyngolaryngeal pain 

(G3/4: 2%) 

Dyspnoea (G3/4: 1%); 

Cough (G3/4: < 1%); 

Epistaxis (G3/4: < 1%) 

Gastrointestinal disorders Stomatitis (G3/4: 18%); 

Diarrhoea (G3/4: 14%); 

Nausea (G3/4: 6%); 

Vomiting (G3/4: 4%); 

Constipation (G3/4: 1%); 

Abdominal pain (G3/4: 2%); 

Dyspepsia 

Abdominal pain upper; 

Dry mouth 

Skin and subcutaneous tissue 

disorders 

Hand-foot syndrome 

(G3/4: 24%); 

Alopecia (G3/4: 6%); 

Nail disorders (G3/4: 2%) 

Dermatitis; 

Rash erythematous 

(G3/4: < 1%); 

Nail discolouration; 

Onycholysis (G3/4: 1%) 

Musculoskeletal and 

connective tissue disorders 

Myalgia (G3/4: 2%); 

Arthralgia (G3/4: 1%) 

Pain in extremity (G3/4: < 1%); 

Back pain (G3/4: 1%) 

General disorders and Asthenia (G3/4: 3%); Lethargy; 



20 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

administration site conditions Pyrexia (G3/4: 1%); 

Fatigue/weakness (G3/4: 5%); 

Oedema peripheral (G3/4: 1%) 

Pain 

Investigations   Weight decreased; 

G3/4 Blood bilirubin increased 

(9%) 

 

Tabulated list of adverse reactions in metastatic castration-resistant prostate cancer for DOCETAXEL 

KABI 75 mg/m² in combination with prednisone or prednisolone 

 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Infections and infestations Infection (G3/4: 3.3%)   

Blood and lymphatic system 

disorders 

Neutropenia (G3/4: 32%); 

Anaemia (G3/4: 4.9%) 

Thrombocytopenia 

(G3/4: 0.6%); 

Febrile neutropenia 

Immune system disorders   Hypersensitivity (G3/4: 0.6%) 

Metabolism and nutrition 

disorders 

Anorexia (G3/4: 0.6%)   

Nervous system disorders Peripheral sensory neuropathy 

(G3/4: 1.2%); 

Dysgeusia (G3/4: 0%) 

Peripheral motor neuropathy 

(G3/4: 0%) 

Eye disorders   Lacrimation increased 

(G3/4: 0.6%) 

Cardiac disorders   Cardiac left ventricular 

function decrease (G3/4: 0.3%) 

Respiratory, thoracic and 

mediastinal disorders 

  Epistaxis (G3/4: 0%); 

Dyspnoea (G3/4: 0.6%); 

Cough (G3/4: 0%) 

Gastrointestinal disorders Nausea (G3/4: 2.4%); 

Diarrhoea (G3/4: 1.2%); 

Stomatitis/Pharyngitis 

(G3/4: 0.9%); 

Vomiting (G3/4: 1.2%) 

  

Skin and subcutaneous tissue 

disorders 

Alopecia; 

Nail disorders (no severe) 

Exfoliative rash (G3/4: 0.3%) 

Musculoskeletal and 

connective bone disorders 

  Arthralgia (G3/4: 0.3%); 

Myalgia (G3/4: 0.3%) 

General disorders and 

administration site conditions 

Fatigue (G3/4: 3.9%); 

Fluid retention (severe: 0.6%) 

  

 



21 

Tabulated list of adverse reactions in high-risk locally advanced or metastatic hormone-sensitive 

prostate cancer for DOCETAXEL KABI 75 mg/m² in combination with prednisone or prednisolone 

and ADT (STAMPEDE study)  

 

MedDRA system organ 

classes 

 

Very common adverse 

reactions 

Common adverse reactions 

Blood and lymphatic system 

disorders 

Neutropenia (G3-4: 12 %) 

Anaemia  

Febrile neutropenia (G3-4: 15%) 

 

Immune system disorders   Hypersensitivity (G3-4: 1%) 

Endocrine disorders  Diabetes (G3-4: 1%) 

Metabolism and nutrition 

disorders 

 Anorexia  

Psychiatric disorders Insomnia (G3: 1%)  

Nervous system disorders Peripheral sensory neuropathy 

(≥G3: 2%)a 

Headache 

 

Dizziness 

Eye disorders  Blurred vision 

Cardiac disorders  Hypotension (G3: 0%) 

 

Respiratory, thoracic and 

mediastinal disorders  

Dyspnea (G3: 1%) 

Coughing (G3: 0%) 

Upper respiratory tract infection 

(G3: 1%)  

Pharyngitis (G3: 0%) 

 

 

Gastrointestinal disorders  Diarrhea (G3: 3%) 

Stomatitis (G3: 0%) 

Constipation (G3: 0%) 

Nausea (G3: 1%) 

Dyspepsia 

Abdominal pain (G3: 0%) 

Flatulence 

Vomiting (G3: 1%) 

 

Skin and subcutaneous tissue 

disorders 

Alopecia (G3: 3%)a 

Nail changes (G3: 1%) 

Rash 

Musculoskeletal and 

connective tissue disorders 

Myalgia   

General disorders and 

administration site conditions 

Lethargy (G3-4: 2%) 

Flu-like symptoms (G3: 0%) 

Asthenia (G3: 0%) 

Fluid retention 

Fever (G3: 1%) 

Oral candidiasis  

Hypocalcaemia (G3: 0%) 

Hypophosphataemia (G3-4: 1%) 

Hypokalaemia (G3: 0%) 
a From the GETUG AFU15 study 
 

Tabulated list of adverse reactions in breast cancer for adjuvant therapy with DOCETAXEL KABI 

75 mg/m² in combination with doxorubicin and cyclophosphamide in patients with node-positive 

(TAX 316) and node-negative (GEICAM 9805) breast cancer - pooled data 

 



22 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 2.4%); 

Neutropenic infection 

(G3/4: 2.6%) 

    

Blood and 

lymphatic system 

disorders 

Anaemia (G3/4: 3%); 

Neutropenia 

(G3/4: 59.2%); 

Thrombocytopenia 

(G3/4: 1.6%); 

Febrile neutropenia 

(G3/4: NA) 

    

Immune system 

disorders 

  Hypersensitivity 

(G3/4: 0.6 %) 

  

Metabolism and 

nutrition disorders 

Anorexia (G3/4: 1.5%)     

Nervous system 

disorders 

Dysgeusia (G3/4: 0.6%); 

Peripheral sensory 

neuropathy 

(G3/4: < 0.1%) 

Peripheral motor 

neuropathy 

(G3/4: 0%) 

Syncope (G3/4: 0%); 

Neurotoxicity 

(G3/4: 0%); 

Somnolence (G3/4: 0%) 

Eye disorders  Conjunctivitis 

(G3/4: < 0.1%) 

Lacrimation 

increased 

(G3/4:  < 0.1%) 

  

Cardiac disorders   Arrhythmia 

(G3/4: 0.2%) 

  

Vascular disorders Hot flush (G3/4: 0.5%) Hypotension 

(G3/4: 0%); 

Phlebitis 

(G3/4: 0%) 

Lymphoedema 

(G3/4: 0%) 

Respiratory, 

thoracic and 

mediastinal 

disorders 

  Cough (G3/4: 0%)   

Gastrointestinal 

disorders 

Nausea (G3/4: 5.0%); 

Stomatitis (G3/4: 6.0%); 

Vomiting (G3/4: 4.2%); 

Diarrhoea (G3/4: 3.4%); 

Constipation 

(G3/4: 0.5%) 

Abdominal pain 

(G3/4: 0.4%) 

 

Skin and 

subcutaneous tissue 

disorders 

Alopecia 

( persisting: < 3%); 

Skin disorder  

(G3/4: 0.6%); 

Nail disorders 

(G3/4: 0.4%) 

    

Musculoskeletal 

and connective 

tissue disorders 

Myalgia (G3/4: 0.7%); 

Arthralgia (G3/4: 0.2%) 

    

Reproductive Amenorrhoea      



23 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

system and breast 

disorders 

(G3/4: NA) 

General disorders 

and administration 

site conditions 

Asthenia  

(G3/4: 10.0%); 

Pyrexia (G3/4: NA); 

Oedema peripheral 

(G3/4: 0.2%) 

    

Investigations   Weight increased 

(G3/4: 0%); 

Weight decreased 

(G3/4: 0.2%) 

  

 

Description of selected adverse reactions for adjuvant therapy with DOCETAXEL KABI 75 mg/m² in 

combination with doxorubicin and cyclophosphamide in patients with node-positive (TAX 

316) and node-negative (GEICAM 9805) breast cancer 

 

Nervous system disorders 

 In study TAX316 peripheral sensory neuropathy started during the treatment period and persisted into 

the follow-up period in 84 patients (11.3%) in TAC arm and 15 patients (2 %) in FAC arm. At the end 

of the follow-up period (median follow-up time of 8 years), peripheral sensory neuropathy was 

observed to be ongoing in 10 patients (1.3%) in TAC arm, and in 2 patients (0.3%) in FAC arm. 

In GEICAM 9805 study peripheral sensory neuropathy that started during the treatment period 

persisted into the follow-up period in 10 patients (1.9%) in TAC arm and 4 patients (0.8 %) in FAC 

arm. At the end of the follow-up period (median follow-up time of 10 years and 5 months), peripheral 

sensory neuropathy was observed to be ongoing in 3 patients (0.6%) in TAC arm, and in 1 patient 

(0.2%) in FAC arm. 

 

Cardiac disorders 

In study TAX316, 26 patients (3.5%) in the TAC arm and 17 patients (2.3%) in the FAC arm 

experienced congestive heart failure. All except one patient in each arm were diagnosed with CHF 

more than 30 days after the treatment period. Two patients in the TAC arm and 4 patients in the FAC 

arm died because of cardiac failure. 

In GEICAM 9805 study, 3 patients (0.6 %) in TAC arm and 3 patients (0.6 %) in FAC arm developed 

congestive heart failure during the follow-up period. At the end of the follow-up period (actual median 

follow-up time of 10 years and 5 months), no patients had CHF in TAC arm and 1 patient in TAC arm 

died because of dilated cardiomyopathy, and CHF was observed to be ongoing in 1 patient (0.2%) in 

FAC arm. 

 

Skin and subcutaneous tissue disorders 

In study TAX316 alopecia persisting into the follow-up period after the end of chemotherapy was 

reported in 687 of 744 TAC patients (92.3%) and 645 of 736 FAC patients (87.6%). 

At the end of the follow-up period (actual median follow-up time of 8 years), alopecia was observed to 

be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%). 

In GEICAM 9805 study alopecia that started during the treatment period and persisted into the follow-

up period was observed to be ongoing in 49 patients (9.2 %) in TAC arm and 35 patients (6.7 %) in 

FAC arm. Alopecia related to study drug started or worsened during the follow-up period in 

42 patients (7.9 %) in TAC arm and 30 patients (5.8 %) in FAC arm. At the end of the follow-up 

period (median follow-up time of 10 years and 5 months), alopecia was observed to be ongoing in 3 

patients (0.6%) in TAC arm, and in 1 patient (0.2%) in FAC arm.   

 

Reproductive system and breast disorders 

 In TAX316 amenorrhoea that started during the treatment period and persisted into the follow-up 

period after the end of chemotherapy was reported in 202 of 744 TAC patients (27.2%) and 125 of 736 



24 

FAC patients (17.0%). Amenorrhea was observed to be ongoing at the end of the follow-up period 

(median follow-up time of 8 years) in 121 of 744 TAC patients (16.3%) and 86 FAC patients (11.7%). 

In GEICAM 9805 study amenorrhoea that started during the treatment period and persisted into the 

follow-up period was observed to be ongoing in 18 patients (3.4 %) in TAC arm and 5 patients (1.0 %) 

in FAC arm. At the end of the follow-up period (median follow-up time of 10 years and 5 months), 

amenorrhoea was observed to be ongoing in 7 patients (1.3%) in TAC arm, and in 4 patients (0.8%) in 

FAC arm. 

  

General disorders and administration site conditions 

In study TAX316 peripheral oedema that started during the treatment period and persisted into the 

follow-up period after the end of chemotherapy was observed in 119 of 744 TAC patients (16.0%) and 

23 of 736 FAC patients (3.1%). At the end of the follow-up period (actual median follow-up time of 8 

years), peripheral oedema was ongoing in19 TAC patients (2.6%) and 4 FAC patients (0.5%).  

In study TAX316 lymphoedema that started during the treatment period and persisted into the follow-

up period after the end of chemotherapy was reported in 11 of 744 TAC patients (1.5%) and 1 of 736 

FAC patients (0.1%). At the end of the follow-up period (actual median follow-up time of 8 years), 

lymphoedema was observed to be ongoing in 6 TAC patients (0.8%) and 1 FAC patient (0.1%). 

In study TAX316 asthenia that started during the treatment period and persisted into the follow-up 

period after the end of chemotherapy was reported in 236 of 744 TAC patients (31.7%) and 180 of 736 

FAC patients (24.5%). At the end of the follow-up period (actual median follow-up time of 8 years), 

asthenia was observed to be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%). 

 

In study GEICAM 9805 peripheral oedema that started during the treatment period persisted into the 

follow-up period in 4 patients (0.8%) in TAC arm and in 2 patients (0.4%) in FAC arm. At the end of 

the follow-up period (median follow-up time of 10 years and 5 months), no patients (0%) in TAC arm 

had peripheral oedema and it was observed to be ongoing in 1 patient (0.2%) in FAC arm. 

Lymphoedema that started during the treatment period persisted into the follow-up period in 5 patients 

(0.9%) in TAC arm and 2 patients (0.4 %) in FAC arm. At the end of the follow-up period, 

lymphoedema was observed to be ongoing in 4 patients (0.8%) in TAC arm, and in 1 patient (0.2%) in 

FAC arm.  

Asthenia that started during the treatment period and persisted into the follow-up period was observed 

to be ongoing in 12 patients (2.3 %) in TAC arm and 4 patients (0.8 %) in FAC arm. At the end of the 

follow-up period, asthenia was observed to be ongoing in 2 patients (0.4%) in TAC arm, and in 2 

patients (0.4%) in FAC arm. 

 

Acute leukaemia / Myelodysplastic syndrome 

After 10 years of follow up in study TAX316, acute leukaemia was reported in 3 of 744 TAC patients 

(0.4%) and in 1 of 736 FAC patients (0.1%). One TAC patient (0.1%) and 1 FAC patient (0.1%) died 

due to AML during the follow-up period (median follow-up time of 8 years). Myelodysplastic 

syndrome was reported in 2 of 744 TAC patients (0.3%) and in 1 of 736 FAC patients (0.1%). 

After 10 years of follow-up in GEICAM 9805 study, acute leukaemia occurred in 1 of 532 (0.2%) 

patients in TAC arm. No cases were reported in patients in FAC arm. No patient was diagnosed with 

myelodysplastic syndrome in either treatment groups. 

 

Neutropenic complications 

Table below shows that the incidence of Grade 4 neutropenia, febrile neutropenia and neutropenic 

infection was decreased in patients who received primary G-CSF prophylaxis after it was made 

mandatory in the TAC arm – GEICAM study. 

 

Neutropenic complications in patients receiving TAC with or without primary G-CSF prophylaxis 

(GEICAM 9805) 

 

 Without primary 

G-CSF prophylaxis 

(n = 111) 

n (%) 

With primary 

G-CSF prophylaxis 

(n = 421) 

n (%) 

Neutropenia (Grade 4) 104 (93.7) 135 (32.1) 



25 

 Without primary 

G-CSF prophylaxis 

(n = 111) 

n (%) 

With primary 

G-CSF prophylaxis 

(n = 421) 

n (%) 

Febrile neutropenia 28 (25.2) 23 (5.5) 

Neutropenic infection 14 (12.6) 21 (5.0) 

Neutropenic infection 

(Grade 3-4) 

2 (1.8) 5 (1.2) 

 

Tabulated list of adverse reactions in gastric adenocarcinoma center for DOCETAXEL KABI 

75 mg/m² in combination with cisplatin and 5-fluorouracil 

 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse reactions 

Infections and 

infestations 

Neutropenic infection; 

Infection (G3/4: 11.7%) 

  

Blood and lymphatic 

system disorders 

Anaemia (G3/4: 20.9%); 

Neutropenia (G3/4: 83.2%); 

Thrombocytopenia (G3/4: 8.8%); 

Febrile neutropenia  

  

Immune system 

disorders 

Hypersensitivity (G3/4: 1.7%)   

Metabolism and 

nutrition disorders 

Anorexia (G3/4: 11.7%)   

Nervous system 

disorders 

Peripheral sensory neuropathy 

(G3/4: 8.7%) 

Dizziness (G3/4: 2.3%); 

Peripheral motor neuropathy 

(G3/4: 1.3%) 

Eye disorders   Lacrimation increased (G3/4: 0%) 

Ear and labyrinth 

disorders 

  Hearing impaired (G3/4: 0%) 

Cardiac disorders   Arrhythmia (G3/4: 1.0%) 

Gastrointestinal 

disorders 

Diarrhoea (G3/4: 19.7%); 

Nausea (G3/4: 16%); 

Stomatitis (G3/4: 23.7%); 

Vomiting (G3/4: 14.3%) 

Constipation (G3/4: 1.0%); 

Gastrointestinal pain (G3/4: 1.0%); 

Oesophagitis/dysphagia/ 

odynophagia (G3/4: 0.7%) 

Skin and subcutaneous 

tissue disorders 

Alopecia (G3/4: 4.0%) Rash pruritus (G3/4: 0.7%); 

Nail disorders (G3/4: 0.7%); 

Skin exfoliation (G3/4: 0%) 

General disorders and 

administration site 

conditions 

Lethargy (G3/4: 19.0%); 

Fever (G3/4: 2.3%); 

Fluid retention (severe/life-

threatening: 1%) 

  

 

Description of selected adverse reactions in gastric adenocarcinoma cancer for DOCETAXEL KABI 

75 mg/m2 in combination with cisplatin and 5-fluorouracil 

 

Blood and lymphatic system disorders 

Febrile neutropenia and neutropenic infection occurred in 17.2% and 13.5% of patients respectively, 

regardless of G-CSF use. G-CSF was used for secondary prophylaxis in 19.3% of patients (10.7% of 

the cycles). Febrile neutropenia and neutropenic infection occurred respectively in 12.1% and 3.4% of 



26 

patients when patients received prophylactic G-CSF, in 15.6% and 12.9% of patients without 

prophylactic G-CSF (see section 4.2). 

 

Tabulated list of adverse reactions in head and neck cancer for DOCETAXEL KABI 75 mg/m² in 

combination with cisplatin and 5-fluorouracil  

 

• Induction chemotherapy followed by radiotherapy (TAX 323)  
 

MedDRA system 

organ classes 

Very common adverse 

reactions 

 

Common adverse 

reactions 

 

Uncommon 

adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 6.3%); 

Neutropenic infection 

    

Neoplasms benign, 

malignant and 

unspecified (incl 

cysts and polyps) 

  Cancer pain (G3/4: 0.6%)   

Blood and lymphatic 

system disorders 

Neutropenia 

(G3/4: 76.3%); 

Anaemia (G3/4: 9.2%); 

Thrombocytopenia 

(G3/4: 5.2%) 

Febrile neutropenia   

Immune system 

disorders 

  Hypersensitivity (no 

severe) 

  

Metabolism and 

nutrition disorders 

Anorexia (G3/4: 0.6%)     

Nervous system 

disorders 

Dysgeusia/Parosmia; 

Peripheral sensory 

neuropathy (G3/4: 0.6%) 

Dizziness   

Eye disorders   Lacrimation increased; 

Conjunctivitis  

  

Ear and labyrinth 

disorders 

  Hearing impaired   

Cardiac disorders   Myocardial ischemia 

(G3/4: 1.7%) 

Arrhythmia 

(G3/4: 0.6%) 

Vascular disorders   Venous disorder 

(G3/4: 0.6%) 

  

Gastrointestinal 

disorders 

Nausea (G3/4: 0.6%); 

Stomatitis (G3/4: 4.0%); 

Diarrhoea (G3/4: 2.9%); 

Vomiting (G3/4: 0.6%) 

Constipation; 

Esophagitis/dysphagia/ 

odynophagia 

(G3/4: 0.6%); 

Abdominal pain; 

Dyspepsia; 

Gastrointestinal 

haemorrhage 

(G3/4: 0.6%)  

  

Skin and 

subcutaneous tissue 

disorders 

Alopecia (G3/4: 10.9%) Rash pruritic; 

Dry skin; 

Skin exfoliative 

(G3/4: 0.6%) 

  



27 

MedDRA system 

organ classes 

Very common adverse 

reactions 

 

Common adverse 

reactions 

 

Uncommon 

adverse 

reactions 

Musculoskeletal and 

connective tissue 

disorders 

  Myalgia (G3/4: 0.6%)   

General disorders and 

administration site 

conditions 

Lethargy (G3/4: 3.4%); 

Pyrexia (G3/4: 0.6%); 

Fluid retention; 

Oedema 

    

Investigations   Weight increased   

 

• Induction chemotherapy followed by chemoradiotherapy (TAX 324)  
 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 3.6%) 

  

Neutropenic 

infection 

  

Neoplasms benign, 

malignant and 

unspecified (incl 

cysts and polyps) 

  Cancer pain 

(G3/4: 1.2%) 

  

Blood and lymphatic 

system disorders 

Neutropenia 

(G3/4: 83.5%); 

Anaemia (G3/4: 12.4%); 

Thrombocytopenia 

(G3/4: 4.0%); 

Febrile neutropenia 

    

Immune system 

disorders 

    Hypersensitivity 

Metabolism and 

nutrition disorders 

Anorexia (G3/4: 12.0%)     

Nervous system 

disorders 

Dysgeusia/Parosmia 

(G3/4: 0.4%); 

Peripheral sensory 

neuropathy (G3/4: 1.2%) 

Dizziness 

(G3/4: 2.0%); 

Peripheral motor 

neuropathy 

(G3/4: 0.4%) 

  

Eye disorders   Lacrimation 

increased 

Conjunctivitis 

Ear and labyrinth 

disorders 

Hearing impaired 

(G3/4: 1.2%) 

    

Cardiac disorders   Arrhythmia 

(G3/4: 2.0%) 

Ischemia myocardial 

Vascular disorders     Venous disorder 

Gastrointestinal 

disorders 

Nausea (G3/4: 13.9%); 

Stomatitis (G3/4: 20.7%); 

Vomiting (G3/4: 8.4%); 

Diarrhoea (G3/4: 6.8%); 

Dyspepsia 

(G3/4: 0.8%); 

Gastrointestinal pain 

(G3/4: 1.2%); 

  



28 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Esophagitis/dysphagia/ 

odynophagia 

(G3/4: 12.0%); 

Constipation (G3/4: 0.4%) 

Gastrointestinal 

haemorrhage 

(G3/4: 0.4%) 

Skin and 

subcutaneous tissue 

disorders 

Alopecia (G3/4: 4.0%); 

Rash pruritic 

Dry skin; 

Desquamation 

  

Musculoskeletal, 

connective tissue 

bone disorders 

  Myalgia 

(G3/4: 0.4%) 

  

General disorders and 

administration site 

conditions 

Lethargy (G3/4: 4.0%); 

Pyrexia (G3/4: 3.6%); 

Fluid retention (G3/4: 1.2); 

Oedema (G3/4: 1.2%) 

    

Investigations Weight decreased   Weight increased 

 

Post-marketing experience 

 

Neoplasms benign, malignant and unspecified (incl cysts and polyps) 

 

Second primary malignancies (frequency not known), including non-Hodgkin lymphoma have been 

reported in association with docetaxel when used in combination with other anticancer treatments 

known to be associated with second primary malignancies. Acute myeloid leukemia and 

myelodysplastic syndrome have been reported (frequency uncommon) in pivotal clinical studies in 

breast cancer with TAC regimen. 

 

Blood and lymphatic system disorders 

Bone marrow suppression and other haematologic adverse reactions have been reported. Disseminated 

intravascular coagulation (DIC), often in association with sepsis or multi-organ failure, has been 

reported. 

 

Immune system disorders 

Some cases of anaphylactic shock, sometimes fatal, have been reported. 

Hypersensitivity reactions (frequency not known) have been reported with docetaxel in patients who 

previously experienced hypersensitivity reactions to paclitaxel. 

 

Nervous system disorders 

Rare cases of convulsion or transient loss of consciousness have been observed with docetaxel 

administration. These reactions sometimes appear during the infusion of the medicinal product. 

 

Eye disorders 

Very rare cases of transient visual disturbances (flashes, flashing lights, scotomata) typically occurring 

during infusion of the medicinal product and in association with hypersensitivity reactions have been 

reported. These were reversible upon discontinuation of the infusion. Cases of lacrimation with or 

without conjunctivitis, as cases of lacrimal duct obstruction resulting in excessive tearing have been 

rarely reported. Cases of cystoid macular oedema (CMO) have been reported in patients treated with 

docetaxel.  

 

Ear and labyrinth disorders 

Rare cases of ototoxicity, hearing impaired and/or hearing loss have been reported. 

 

 



29 

Cardiac disorders 

Rare cases of myocardial infarction have been reported. 

Ventricular arrhythmia including ventricular tachycardia (frequency not known), sometimes fatal, has 

been reported in patients treated with docetaxel in combination regimens including doxorubicin, 5-

fluorouracil and/ or cyclophosphamide. 

 

Vascular disorders 

Venous thromboembolic events have rarely been reported. 

 

Respiratory, thoracic and mediastinal disorders 

Acute respiratory distress syndrome and cases of interstitial pneumonia/ pneumonitis, interstitial lung 
disease, pulmonary fibrosis and respiratory failure sometimes fatal have rarely been reported. Rare 

cases of radiation pneumonitis have been reported in patients receiving concomitant radiotherapy. 

 

Gastrointestinal disorders 

Rare cases of enterocolitis, including colitis, ischemic colitis, and neutropenic enterocolitis, have been 

reported with a potential fatal outcome (frequency not known). 

Rare occurrences of dehydration have been reported as a consequence of gastrointestinal events 

including enterocolitis and gastrointestinal perforation.  

Rare cases of ileus and intestinal obstruction have been reported. 

  

Hepatobiliary disorders 

Very rare cases of hepatitis, sometimes fatal primarily in patients with pre-existing liver disorders, 

have been reported. 

 

Skin and subcutaneous tissue disorders 

Cases of cutaneous lupus erythematosus, bullous eruptions such as erythema multiforme and severe 

cutaneous adverse reactions such as Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis 

(TEN) and Acute Generalized Exanthematous Pustulosis (AGEP) have been reported with docetaxel.  

Scleroderma-like changes usually preceded by peripheral lymphoedema have been reported with 

docetaxel. Cases of permanent alopecia (frequency not known) have been reported. 

 

Renal and urinary disorders 

Renal insufficiency and renal failure have been reported. In about 20% of these cases there were no 

risk factors for acute renal failure such as concomitant nephrotoxic medicinal products and 

gastrointestinal disorders. 

 

General disorders and administration site conditions 

Radiation recall phenomena have rarely been reported. 

Injection site recall reaction (recurrence of skin reaction at a site of previous extravasation following 

administration of docetaxel at a different site) has been observed at the site of previous extravasation 

(frequency not known). 

Fluid retention has not been accompanied by acute episodes of oliguria or hypotension. Dehydration 

and pulmonary oedema have rarely been reported. 

 

Metabolism and nutrition disorders 

Cases of electrolyte imbalance have been reported. Cases of hyponatraemia have been reported, 

mostly associated with dehydration, vomiting and pneumonia. Hypokalaemia, hypomagnesaemia, and 

hypocalcaemia were observed, usually in association with gastrointestinal disorders and in particular 

with diarrhoea. 

 
Reporting of suspected adverse reactions 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 



30 

 

4.9 Overdose 

 

There were a few reports of overdose. There is no known antidote for docetaxel overdose. In case of 

overdose, the patient should be kept in a specialised unit and vital functions closely monitored. In 

cases of overdose, exacerbation of adverse events may be expected. The primary anticipated 

complications of overdose would consist of bone marrow suppression, peripheral neurotoxicity and 

mucositis. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. 

Other appropriate symptomatic measures should be taken, as needed. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: antineoplastic agents, plant alkaloids and other natural products, taxanes, 

ATC Code: L01CD02  

 

Mechanism of action 

 

Docetaxel is an antineoplastic agent which acts by promoting the assembly of tubulin into stable 

microtubules and inhibits their disassembly which leads to a marked decrease of free tubulin. The 

binding of docetaxel to microtubules does not alter the number of protofilaments. 

 

Docetaxel has been shown in vitro to disrupt the microtubular network in cells which is essential for 

vital mitotic and interphase cellular functions. 

 

Pharmacodynamic effects 

 

Docetaxel was found to be cytotoxic in vitro against various murine and human tumour cell lines and 

against freshly excised human tumour cells in clonogenic assays. Docetaxel achieves high intracellular 

concentrations with a long cell residence time. In addition, docetaxel was found to be active on some 

but not all cell lines over expressing the p-glycoprotein which is encoded by the multidrug resistance 

gene. In vivo, docetaxel is schedule independent and has a broad spectrum of experimental anti-tumour 

activity against advanced murine and human grafted tumours. 

 

Clinical efficacy and safety 

 

Breast cancer 

 

DOCETAXEL KABI in combination with doxorubicin and cyclophosphamide: adjuvant therapy 

 

Patients with operable node-positive breast cancer (TAX 316) 

 

Data from a multi-centre open-label randomised study support the use of docetaxel for the adjuvant 
treatment of patients with operable node-positive breast cancer and KPS ≥ 80%, between 18 and 

70 years of age. After stratification according to the number of positive lymph nodes (1-3, 

4+), 1491 patients were randomised to receive either docetaxel 75 mg/m2 administered 1-hour after 

doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (TAC arm), or doxorubicin 50 mg/m2 

followed by fluorouracil 500 mg/m2 and cyclosphosphamide 500 mg/m2 (FAC arm). Both regimens 

were administered once every 3 weeks for 6 cycles. Docetaxel was administered as a 1-hour infusion, 

all other medicinal products were given as intravenous bolus on day one. G-CSF was administered as 

secondary prophylaxis to patients who experienced complicated neutropenia (febrile neutropenia, 

prolonged neutropenia, or infection). Patients on the TAC arm received antibiotic prophylaxis with 

ciprofloxacin 500 mg orally twice daily for 10 days starting on day 5 of each cycle, or equivalent. In 

both arms, after the last cycle of chemotherapy, patients with positive oestrogen and/or progesterone 

receptors received tamoxifen 20 mg daily for up to 5 years. Adjuvant radiation therapy was prescribed 



31 

according to guidelines in place at participating institutions and was given to 69% of patients who 

received TAC and 72% of patients who received FAC. Two interim analyses and one final analysis 

were performed. The first interim analysis was planned 3 years after the date when half of study 

enrolment was done. The second interim analysis was done after 400 DFS events had been recorded 

overall, which led to a median follow-up of 55 months. The final analysis was performed when all 

patients had reached their 10-year follow-up visit (unless they had a DFS event or were lost to follow 

up before). Disease-free survival (DFS) was the primary efficacy endpoint and Overall survival (OS) 

was the secondary efficacy endpoint. 

 

A final analysis was performed with an actual median follow up of 96 months. Significantly longer 

disease-free survival for the TAC arm compared to the FAC arm was demonstrated. Incidence of 

relapses at 10 years was reduced in patients receiving TAC compared to those who received FAC 

(39% versus 45%, respectively) i.e. an absolute risk reduction by 6% (p = 0.0043). Overall survival at 

10 years was also significantly increased with TAC compared to FAC (76% versus 69%, respectively) 

i.e. an absolute reduction of the risk of death by 7% (p = 0.002). As the benefit observed in patients 

with 4+ nodes was not statistically significant on DFS and OS, the positive benefit/risk ratio for TAC 

in patients with 4+ nodes was not fully demonstrated at the final analysis. 

 

Overall, the study results demonstrate a positive benefit risk ratio for TAC compared to FAC. 

 

TAC-treated patient subsets according to prospectively defined major prognostic factors were 

analysed:  

 

  Disease free survival Overall Survival 

Patient 

subset 

Number 

of patients 

Hazard 

ratio* 

95% CI p = Hazard 

ratio* 

95% CI p = 

No of 

positive 

nodes 

Overall 

1-3 

4+ 

 

 

 

745 

467 

278 

 

 

 

0.80 

0.72 

0.87 

 

 

 

0.68-0.93 

0.58-0.91 

0.70-1.09 

 

 

 

0.0043 

0.0047 

0.2290 

 

 

 

0.74 

0.62 

0.87 

 

 

 

0.61-0.90 

0.46-0.82 

0.67-1.12 

 

 

 

0.0020 

0.0008 

0.2746 

*a hazard ratio of less than 1 indicates that TAC is associated with a longer disease-free survival and 

overall survival compared to FAC  

 

Patients with operable node-negative breast cancer eligible to receive chemotherapy (GEICAM 9805) 

 

Data from a multi-centre open- label randomised trial support the use of DOCETAXEL KABI for the 
adjuvant treatment of patients with operable node-negative breast cancer eligible to receive 

chemotherapy. 1060 patients were randomised to receive either DOCETAXEL KABI 75 mg/m2 

administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (539 patients in 

TAC arm), or doxorubicin 50 mg/m2 followed by fluorouracil 500 mg/m2 and cyclosphosphamide 

500 mg/m2 (521 patients in FAC arm), as adjuvant treatment of operable node-negative breast cancer 

patients with high risk of relapse according to 1998 St. Gallen criteria (tumour size > 2 cm and/or 

negative ER and PR and/or high histological/nuclear grade (grade 2 to 3) and /or age < 35 years).). 

Both regimens were administered once every 3 weeks for 6 cycles. DOCETAXEL KABI was 

administered as a 1-hour infusion, all other medicinal product were given intraveinously on day 1 

every three weeks. Primary prophylactic G-CSF was made mandatory in TAC arm after 230 patients 

were randomised. The incidence of Grade 4 neutropenia, febrile neutropenia and neutropenic infection 

was decreased in patients who received primary G-CSF prophylaxis (see section 4.8). In both arms, 

after the last cycle of chemotherapy, patients with ER+ and/or PgR+ tumours received tamoxifen 

20 mg once a day for up to 5 years. Adjuvant radiation therapy was administered according to 

guidelines in place at participating institutions and was given to 57.3% of patients who received TAC 

and 51.2% of patients who received FAC. 

 



32 

One primary analysis and one updated analysis were performed. The primary analysis was done when 

all patients had a follow-up of greater than 5 years (median follow-up time of 77 months). The updated 

analysis was performed when all patients had reached their 10-year (median follow up time of 10 

years and 5 months) follow-up visit (unless they had a DFS event or were lost to follow-up 

previously). Disease-free survival (DFS) was the primary efficacy endpoint and Overall survival (OS) 

was the secondary efficacy endpoint. 

 

At the median follow-up was time of 77 months significantly longer disease-free survival for the TAC 

arm compared to the FAC arm was demonstrated. TAC-treated patients had a 32% reduction in the 

risk of relapse compared to those treated with FAC (hazard ratio = 0.68, 95% CI (0.49-0.93), 

p = 0.01). At the median follow up time of 10 years and 5 months, TAC-treated patients had a 16,5% 

reduction in the risk of relapse compared to those treated with FAC (hazard ratio = 0.84, 95% CI 

(0.65-1.08), p=0.1646). DFS data were not statistically significant but were still associated with a 

positive trend in favour of TAC 

 

At the median follow-up time of 77 months overall survival (OS) was longer in the TAC arm with 

TAC-treated patients having a 24% reduction in the risk of death compared to FAC (hazard ratio = 

0.76, 95% CI (0.46-1.26, p = 0.29). However, the distribution of OS was not significantly different 

between the 2 groups. 

At the median follow up time of 10 years and 5 months, TAC-treated patients had a 9% reduction in 

the risk of death compared to FAC-treated patients (hazard ratio = 0.91, 95% CI (0.63-1.32)). The 

survival rate was 93.7% in the TAC arm and 91.4 % in the FAC arm, at the 8-year follow-up time 

point, and 91.3 % in the TAC arm and 89 % in the FAC arm, at the 10-year follow-up time point. 

 

The positive benefit risk ratio for TAC compared to FAC remained unchanged 

 

TAC-treated patient subsets according to prospectively defined major prognostic factors were 

analyzed in the primary analysis (at the median follow-up time of 77 months) (see table below): 

 

Subset Analyses-Adjuvant Therapy in Patients with Node-negative Breast Cancer Study 

(Intent-to-Treat Analysis) 

 

Patient subset Number of patients 

in TAC group 

Disease Free Survival 

Hazard ratio* 95% CI 

Overall 539 0.68 0.49-0.93 

Age category 1 

<50 years  

≥50 years 

 

260 

279  

 

0.67 

0.67  

 

0.43-1.05 

0.43-1.05 

Age category 2 

<35 years 

≥35 years 

 

42 

497 

 

0.31 

0.73 

 

0.11-0.89 

0.52-1.01 

Hormonal receptor 

status 

Negative  

Positive 

 

 

195 

344 

 

 

0.7 

0.62 

 

 

0.45-1.1 

0.4-0.97 

Tumour size 

≤2 cm  

>2 cm 

 

285 

254 

 

0.69 

0.68 

 

0.43-1.1 

0.45-1.04 

Histological grade 

Grade1 (includes grade 

not assessed) 

Grade 2  

Grade 3 

 

64 

 

216 

259 

 

0.79 

 

0.77 

0.59 

 

0.24-2.6 

 

0.46-1.3 

0.39-0.9 

Menopausal status 

Pre-Menopausal  

Post-Menopausal  

 

285 

254 

 

0.64 

0.72 

 

0.40-1 

0.47-1.12 



33 

*a hazard ratio (TAC/FAC) of less than 1 indicates that TAC is associated with a longer disease free 

survival compared to FAC. 

 

Exploratory subgroup analyses for disease-free survival for patients who meet the 2009 St. Gallen 

chemotherapy criteria – (ITT population) were performed and presented here below 

 
 TAC 

 

FAC 

 

Hazard ratio 

(TAC/FAC) 

 

 

Subgroups (n=539) (n=521) (95% CI) p-value 

Meeting relative 

 indication 

for chemotherapya 

    

No 18/214 

(8.4%) 

26/227 

(11.5%) 

0.796 

(0.434 - 1.459) 

0.4593 

Yes 48/325 

(14.8%) 

69/294 

(23.5%) 

0.606 

(0.42 - 0.877) 

0.0072 

TAC = docetaxel, doxorubicin and cyclophosphamide 

FAC = 5-fluorouracil, doxorubicin and cyclophosphamide 

CI = confidence interval 

ER = oestrogen receptor 

PR = progesterone receptor 
a ER/PR-negative or Grade 3 or tumour size > 5 cm 

 

The estimated hazard ratio was using Cox proportional hazard model with treatment group as the 

factor. 

 

DOCETAXEL KABI as single agent 

 

Two randomised phase III comparative studies, involving a total of 326 alkylating or 

392 anthracycline failure metastatic breast cancer patients, have been performed with docetaxel at the 

recommended dose and regimen of 100 mg/m² every 3 weeks. 

 

In alkylating-failure patients, docetaxel was compared to doxorubicin (75 mg/m² every 3 weeks). 

Without affecting overall survival time (docetaxel 15 months vs. doxorubicin 14 months, p = 0.38) or 

time to progression (docetaxel 27 weeks vs. doxorubicin 23 weeks, p = 0.54), docetaxel increased 

response rate (52% vs. 37%, p = 0.01) and shortened time to response (12 weeks vs. 23 weeks, 

p= 0.007). Three docetaxel patients (2%) discontinued the treatment due to fluid retention, whereas 

15 doxorubicin patients (9%) discontinued due to cardiac toxicity (three cases of fatal congestive heart 

failure). 

 

In anthracycline-failure patients, docetaxel was compared to the combination of mitomycin C and 

vinblastine (12 mg/m² every 6 weeks and 6 mg/m² every 3 weeks). Docetaxel increased response rate 

(33% vs. 12%, p < 0.0001), prolonged time to progression (19 weeks vs. 11 weeks, p= 0.0004) and 

prolonged overall survival (11 months vs. 9 months, p= 0.01). 

 

During these two phase III studies, the safety profile of docetaxel was consistent with the safety profile 

observed in phase II studies (see section 4.8). 

 

An open-label, multi-centre, randomised phase III study was conducted to compare docetaxel 

monotherapy and paclitaxel in the treatment of advanced breast cancer in patients whose previous 

therapy should have included an anthracycline. A total of 449 patients were randomised to receive 

either docetaxel monotherapy 100 mg/m² as a 1 hour infusion or paclitaxel 175 mg/m² as a 3 hour 

infusion. Both regimens were administered every 3 weeks. 

Without affecting the primary endpoint, overall response rate (32% vs 25%, p = 0.10), docetaxel 

prolonged median time to progression (24.6 weeks vs 15.6 weeks; p < 0.01) and median survival 

(15.3 months vs 12.7 months; p = 0.03). 



34 

More grade 3/4 adverse events were observed for docetaxel monotherapy (55.4%) compared to 

paclitaxel (23.0%). 

 

DOCETAXEL KABI in combination with doxorubicin 

 

One large randomised phase III study, involving 429 previously untreated patients with metastatic 

disease, has been performed with doxorubicin (50 mg/m²) in combination with docetaxel (75 mg/m²) 

(AT arm) versus doxorubicin (60 mg/m²) in combination with cyclophosphamide (600 mg/m²) (AC 

arm). Both regimens were administered on day 1 every 3 weeks.  

 

• Time to progression (TTP) was significantly longer in the AT arm versus AC arm, p = 0.0138. 
The median TTP was 37.3 weeks (95% CI: 33.4 - 42.1) in AT arm and 31.9 weeks (95% CI: 27.4 - 

36.0) in AC arm.  

• Overall response rate (ORR) was significantly higher in the AT arm versus AC arm, p = 0.009. 
The ORR was 59.3% (95% CI: 52.8 - 65.9) in AT arm versus 46.5% (95% CI: 39.8 - 53.2) in AC 

arm.  

 

In this study, AT arm showed a higher incidence of severe neutropenia (90% versus 68.6%), febrile 

neutropenia (33.3% versus 10%), infection (8% versus 2.4%), diarrhoea (7.5% versus 1.4%), asthenia 

(8.5% versus 2.4%), and pain (2.8% versus 0%) than AC arm. On the other hand, AC arm showed a 

higher incidence of severe anaemia (15.8% versus 8.5%) than AT arm, and, in addition, a higher 

incidence of severe cardiac toxicity: congestive heart failure (3.8% versus 2.8%), absolute LVEF 

decrease ≥ 20% (13.1% versus 6.1%), absolute LVEF decrease ≥ 30% (6.2% versus 1.1%). Toxic 

deaths occurred in 1 patient in the AT arm (congestive heart failure) and in 4 patients in the AC arm 

(1 due to septic shock and 3 due to congestive heart failure).  

In both arms, quality of life measured by the EORTC questionnaire was comparable and stable during 

treatment and follow-up.  

 

DOCETAXEL KABI in combination with trastuzumab 

 

Docetaxel in combination with trastuzumab was studied for the treatment of patients with metastatic 

breast cancer whose tumours overexpress HER2, and who previously had not received chemotherapy 

for metastatic disease. One hundred eighty six patients were randomised to receive docetaxel 

(100 mg/m2) with or without trastuzumab; 60% of patients received prior anthracycline-based adjuvant 

chemotherapy. Docetaxel plus trastuzumab was efficacious in patients whether or not they had 

received prior adjuvant anthracyclines. The main test method used to determine HER2 positivity in 

this pivotal study was immunohistochemistry (IHC). A minority of patients were tested using 

fluorescence in-situ hybridization (FISH). In this study, 87% of patients had disease that was IHC 3+, 

and 95% of patients entered had disease that was IHC 3+ and/or FISH positive. Efficacy results are 

summarized in the following table:  

 

Parameter Docetaxel plus trastuzumab1 

n = 92 

Docetaxel1 

n = 94 

Response rate 

(95% CI) 

61% 

(50-71) 

34% 

(25-45) 

Median duration of response 

(months) 

(95% CI)  

11.4 

(9.2-15.0) 

5.1 

(4.4-6.2) 

Median TTP (months) 

(95% CI) 

10.6 

(7.6-12.9) 

5.7 

(5.0-6.5) 

Median survival (months) 

(95% CI) 

30.52 

(26.8-ne) 

22.12 

(17.6-28.9) 

TTP = time to progression; “ne” indicates that it could not be estimated or it was not yet reached.  
1Full analysis set (intent-to-treat)  



35 

2 Estimated median survival  

 

DOCETAXEL KABI in combination with capecitabine 

 

Data from one multi-centre, randomised, controlled phase III clinical study support the use of 

docetaxel in combination with capecitabine for treatment of patients with locally advanced or 

metastatic breast cancer after failure of cytotoxic chemotherapy, including an anthracycline. In this 

study, 255 patients were randomised to treatment with docetaxel (75 mg/m2 as a 1 hour intravenous 

infusion every 3 weeks) and capecitabine (1250 mg/m2 twice daily for 2 weeks followed by 1-week 

rest period). 256 patients were randomised to treatment with docetaxel alone (100 mg/m2 as a 1 hour 

intravenous infusion every 3 weeks). Survival was superior in the docetaxel + capecitabine 

combination arm (p = 0.0126). Median survival was 442 days (docetaxel + capecitabine) vs. 352 days 

(docetaxel alone). The overall objective response rates in the all-randomised population (investigator 

assessment) were 41.6% (docetaxel + capecitabine) vs. 29.7% (docetaxel alone); p = 0.0058. Time to 

progressive disease was superior in the docetaxel + capecitabine combination arm (p < 0.0001). The 

median time to progression was 186 days (docetaxel + capecitabine) vs. 128 days (docetaxel alone). 

 

Non-small cell lung cancer 

 

Patients previously treated with chemotherapy with or without radiotherapy 

 

In a phase III study, in previously treated patients, time to progression (12.3 weeks versus 7 weeks) 

and overall survival were significantly longer for docetaxel at 75 mg/m² compared to Best Supportive 

Care. The 1-year survival rate was also significantly longer in docetaxel (40%) versus BSC (16%). 

There was less use of morphinic analgesic (p < 0.01), non-morphinic analgesics (p < 0.01), other 

disease-related medicinal products (p = 0.06) and radiotherapy (p < 0.01) in patients treated with 

docetaxel at 75 mg/m² compared to those with BSC.  

The overall response rate was 6.8% in the evaluable patients, and the median duration of response was 

26.1 weeks.  

 

DOCETAXEL KABI in combination with platinum agents in chemotherapy-naïve patients 

 

In a phase III study, 1218 patients with unresectable stage IIIB or IV NSCLC, with KPS of 70% or 

greater, and who did not receive previous chemotherapy for this condition, were randomised to either 

docetaxel (T) 75 mg/m2 as a 1 hour infusion immediately followed by cisplatin (Cis) 75 mg/m2 over 

30-60 minutes every 3 weeks (TCis), docetaxel 75 mg/m2 as a 1 hour infusion in combination with 

carboplatin (AUC 6 mg/ml.min) over 30-60 minutes every 3 weeks, or vinorelbine (V) 25 mg/m2 

administered over 6-10 minutes on days 1, 8, 15, 22 followed by cisplatin 100 mg/m2 administered on 

day 1 of cycles repeated every 4 weeks (VCis).  

 

Survival data, median time to progression and response rates for two arms of the study are illustrated 

in the following table:  

 

 TCis 

n = 408 

VCis 

n = 404 

Statistical analysis 

Overall survival 

(Primary end-point): 

   

Median survival (months) 11.3 10.1 Hazard Ratio: 1.122 

 [97.2% CI: 0.937; 1.342]* 

1-year Survival (%) 46 41 Treatment difference: 5.4% 

[95% CI: -1.1; 12.0] 

2 year Survival (%) 21 14 Treatment difference: 6.2% 

[95% CI: 0.2; 12.3] 

Median time to progression 

(weeks): 

22.0 23.0 Hazard Ratio: 1.032  

[95% CI: 0.876; 1.216] 

Overall response rate (%): 31.6 24.5 Treatment difference: 7.1% 

[95% CI: 0.7; 13.5] 



36 

*: Corrected for multiple comparisons and adjusted for stratification factors (stage of disease and 

region of treatment), based on evaluable patient population. 

 

Secondary end-points included change of pain, global rating of quality of life by EuroQoL-5D, Lung 

Cancer Symptom Scale, and changes in Karnosfky performance status. Results on these end-points 

were supportive of the primary end-points results.  

 

For docetaxel/carboplatin combination, neither equivalent nor non-inferior efficacy could be proven 

compared to the reference treatment combination VCis.  

 

Prostate cancer 

Metastatic castration-resistant prostate cancer 

 

The safety and efficacy of docetaxel in combination with prednisone or prednisolone in patients with 

metastatic castration-resistant prostate cancer were evaluated in a randomised multi-centre phase III 
study (TAX 327). A total of 1006 patients with KPS ≥ 60 were randomised to the following treatment 

groups:  

• Docetaxel 75 mg/m2 every 3 weeks for 10 cycles. 

• Docetaxel 30 mg/m2 administered weekly for the first 5 weeks in a 6 week cycle for 5 cycles. 

• Mitoxantrone 12 mg/m2 every 3 weeks for 10 cycles. 
All 3 regimens were administered in combination with prednisone or prednisolone 5 mg twice daily, 

continuously. 

 

Patients who received docetaxel every three weeks demonstrated significantly longer overall survival 

compared to those treated with mitoxantrone. The increase in survival seen in the docetaxel weekly 

arm was not statistically significant compared to the mitoxantrone control arm. Efficacy endpoints for 

the docetaxel arms versus the control arm are summarized in the following table:  

 

Endpoint 

 

Docetaxel every 3 

weeks 

Docetaxel every 

week 

Mitoxantrone 

every 3 weeks 

Number of patients 

Median survival (months) 

95% CI 

Hazard ratio 

95% CI 

p-value† * 

335 

18.9 

(17.0-21.2) 

0.761 

(0.619-0.936) 

0.0094 

334 

17.4 

(15.7-19.0) 

0.912 

(0.747-1.113) 

0.3624 

337 

16.5 

(14.4-18.6) 

- 

- 

- 

Number of patients 

PSA** response rate (%) 

95% CI 

p-value* 

291 

45.4 

(39.5-51.3) 

0.0005 

282 

47.9 

(41.9-53.9) 

< 0.0001 

300 

31.7 

(26.4-37.3) 

- 

Number of patients 

Pain response rate (%) 

95% CI 

p-value* 

153 

34.6 

(27.1-42.7) 

0.0107 

154 

31.2 

(24.0-39.1) 

0.0798 

157 

21.7 

(15.5-28.9) 

- 

Number of patients 

Tumor response rate (%) 

95% CI 

p-value* 

141 

12.1 

(7.2-18.6) 

0.1112 

134 

8.2 

(4.2-14.2) 

0.5853 

137 

6.6 

(3.0-12.1) 

- 
†Stratified log-rank test  

*Threshold for statistical significance = 0.0175  

**PSA: Prostate-Specific Antigen  

 

Given the fact that docetaxel every week presented a slightly better safety profile than docetaxel every 

3 weeks, it is possible that certain patients may benefit from docetaxel every week.  



37 

 

No statistical differences were observed between treatment groups for Global Quality of Life. 

 

Metastatic hormone-sensitive prostate cancer 

 

STAMPEDE study 

 

The safety and efficacy of docetaxel administered concomitantly with standard of care (ADT) in 

patients with high-risk locally advanced or metastatic hormone-sensitive prostate cancer were 

evaluated in a randomised multi-centre, multi-arm multi-stage (MAMS) study with a seamless phase 

II/III design (STAMPEDE – MRC PR08). A total of 1776 male patients were allocated to the 
treatment arms of interest:  

• Standard of care + docetaxel 75 mg/m², administered every 3 weeks for 6 cycles 

• Standard of care alone  

Docetaxel regimen was administered in combination with prednisone or prednisolone 5 mg twice daily 

continuously.  

Among the 1776 randomised patients 1086 (61%) had metastatic disease, 362 were randomised to 

docetaxel in combination with standard of care, 724 received standard of care alone.  

 

In these metastatic prostate cancer patients, the median overall survival was significantly longer in 

docetaxel treatment groups than in the standard of care alone group, with a median overall survival 19 

months longer with the addition of docetaxel to standard of care (HR =  0.76, 95% CI = 0.62-0.92, 

p=0.005).  

 

Efficacy results in metastatic prostate cancer patients for docetaxel arm versus control arm are 

summarized in the following table: 

 

Efficacy of docetaxel in combination with prednisone or prednisolone and standard of care in the 

treatment of patients with metastatic hormone-sensitive prostate cancer (STAMPEDE) 

 

Endpoint 

 

Docetaxel + standard of care 

 

Standard of care alone 

Number of metastatic prostate 

cancer patients 

 

Median overall survival (months)  

95% CI 

362 

 

 

62 

51-73 

724 

 

 

43 

40-48 

Adjusted hazard ratio 

95% CI 

p-valuea 

0.76 

(0.62-0.92) 

0.005 

Failure-Free survivalb    

Median (months) 

95% CI 

20.4 

16.8-25.2 

12 

9.6-12 

Adjusted hazard ratio 

95% CI 

p-valuea 

0.66 

(0.57-0.76) 

< 0.001 

a p-value calculated from the likelihood ratio test and adjusted for all stratification factors 

(except center and planned hormone therapy) and stratified by trial period 
b Failure-free survival: time from randomization to first evidence of at least one of: biochemical 

failure (defined as a rise in PSA of 50% above the within-24-week nadir and above 4 ng/mL 

and confirmed by retest or treatment); progression either locally, in lymph nodes, or in distant 

metastases; skeletal-related event; or death from prostate cancer. 

 



38 

CHAARTED study 

 

The safety and efficacy of docetaxel administered at the beginning of androgen-deprivation therapy 

(ADT) in patients with metastatic hormone-sensitive prostate cancer were evaluated in a randomised 

Phase III multi-centre study (CHAARTED). A total of 790 male patients were allocated to the 2 

treatment groups.  

• ADT + docetaxel 75 mg/m² given at the beginning of ADT, administered every 3 weeks 

for 6 cycles 

• ADT alone   

 

The median overall survival was significantly longer in docetaxel treatment group than in the ADT 

alone group, with a median overall survival 13.6 months longer with the addition of docetaxel to ADT 

(hazard ratio (HR) = 0.61, 95% confidence interval (CI) = 0.47-0.80, p=0.0003).  

 

Efficacy results or the docetaxel arm versus the control arm are summarized in the following table: 

 

Efficacy of docetaxel and ADT in the treatment of patients with metastatic hormone-sensitive prostate 

cancer (CHAARTED) 

 

Endpoint 

 

Docetaxel +ADT  

 

ADT alone 

Number of patients 

Median overall survival (months) 

All patients 

95% CIAdjusted hazard ratio 

397 

 

57.6 

49.1-72.8 

0.61 

393 

 

44.0 

34.4-49.1 

-- 

95% CI (0.47-0.80)  -- 

p-valuea 0.0003 -- 

Progression Free Survival 

Median (months) 

95% CI 

Adjusted hazard ratio 
95% CI 

p-value* 

 

19.8 

16.7-22.8 

0.60 

0.51-0.72 

P<0.0001 

 

11.6 

10.8-14.3 

-- 

-- 

-- 

PSA response** at 6 months – N(%) 

p-valuea* 

127 (32.0) 

<0.0001 

77 (19.6) 

-- 

PSA response** at 12 months – N(%) 

p-valuea* 

110 (27.7) 

<0.0001 

66 (16.8) 

-- 

Time to castration-resistant prostate cancerb   

Median (months)  

95% CI 

Adjusted hazard ratio 

20.2 

(17.2-23.6) 

0.61 

11.7 

(10.8-14.7) 

-- 

95% CI (0.51-0.72) -- 

p-valuea* <0.0001 -- 

Time to clinical progressionc    

Median (months)  33.0 19.8 

95% CI (27.3-41.2) (17.9-22.8) 

Adjusted hazard ratio 0.61 -- 

95% CI (0.50-0.75) -- 

p-valuea* <0.0001 -- 



39 

a Time to event variables: Stratified log-rank test.  

  Response rate variables: Fisher's Exact test  

* p-value for descriptive purpose. 

** PSA response: Prostate-Specific Antigen response: PSA level <0.2 ng/mL measured for two 

consecutive measurements at least 4 weeks apart. 

b Time to castration-resistant prostate cancer = time from randomization to PSA progression or 

clinical progression (i.e., increasing symptomatic bone metastases, progression per Response 

Evaluation Criteria in Solid Tumours (RECIST) criteria, or clinical deterioration due to cancer 

per the Investigator’s opinion), whichever occurred first. 
c The time to clinical progression = the time from randomization until clinical progression (i.e., 

increased symptoms of bone metastases; progression according to RECIST; or clinical deterioration 

due to cancer according to the investigator’s opinion). 

 

Gastric adenocarcinoma 

 

A multi-centre, open-label, randomised study, was conducted to evaluate the safety and efficacy of 

docetaxel for the treatment of patients with metastatic gastric adenocarcinoma, including 

adenocarcinoma of the gastroesophageal junction, who had not received prior chemotherapy for 

metastatic disease. A total of 445 patients with KPS > 70 were treated with either docetaxel (T) 

(75 mg/m2 on day 1) in combination with cisplatin (C) (75 mg/m2 on day 1) and 5-fluorouracil (F) 

(750 mg/m2 per day for 5 days) or cisplatin (100 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2 per 

day for 5 days). The length of a treatment cycle was 3 weeks for the TCF arm and 4 weeks for the CF 

arm. The median number of cycles administered per patient was 6 (with a range of 1-16) for the TCF 

arm compared to 4 (with a range of 1-12) for the CF arm. Time to progression (TTP) was the primary 

endpoint. The risk reduction of progression was 32.1% and was associated with a significantly longer 

TTP (p = 0.0004) in favour of the TCF arm. Overall survival was also significantly longer 

(p = 0.0201) in favour of the TCF arm with a risk reduction of mortality of 22.7%. Efficacy results are 

summarized in the following table: 

 

Efficacy of docetaxel in the treatment of patients with gastric adenocarcinoma 

 

Endpoint TCF 

n = 221 

CF 

n = 224 

Median TTP (months) 

(95% CI) 

Hazard ratio 

(95% CI) 

*p-value 

5.6 

(4.86-5.91) 

3.7 

(3.45-4.47) 

1.473 

(1.189-1.825) 

0.0004 

Median survival (months) 

(95% CI) 

2-year estimate (%) 

Hazard ratio 

(95% CI) 

*p-value 

9.2 

(8.38-10.58) 

18.4 

8.6 

(7.16-9.46) 

8.8 

1.293 

(1.041-1.606) 

0.0201 

Overall Response Rate (CR+PR) (%) 

p-value 

36.7 25.4 

0.0106 

Progressive Disease as Best Overall Response (%) 16.7 25.9 

*Unstratified logrank test  

 

Subgroup analyses across age, gender and race consistently favoured the TCF arm compared to the CF 

arm.  



40 

 

A survival update analysis conducted with a median follow-up time of 41.6 months no longer showed 

a statistically significant difference although always in favour of the TCF regimen and showed that the 

benefit of TCF over CF is clearly observed between 18 and 30 months of follow up.  

 

Overall, quality of life (QoL) and clinical benefit results consistently indicated improvement in favour 

of the TCF arm. Patients treated with TCF had a longer time to 5% definitive deterioration of global 

health status on the QLQ-C30 questionnaire (p = 0.0121) and a longer time to definitive worsening of 

Karnofsky performance status (p = 0.0088) compared to patients treated with CF. 

 

Head and neck cancer 

 

• Induction chemotherapy followed by radiotherapy (TAX323)  
The safety and efficacy of docetaxel in the induction treatment of patients with squamous cell 

carcinoma of the head and neck (SCCHN) was evaluated in a phase III, multi-centre, open-label, 

randomised study (TAX323). In this study, 358 patients with inoperable locally advanced SCCHN, 

and WHO performance status 0 or 1, were randomised to one of two treatment arms. Patients on the 

docetaxel arm received docetaxel (T) 75 mg/m2 followed by cisplatin (P) 75 mg/m2 followed by 

5-fluorouracil (F) 750 mg/m2 per day as a continuous infusion for 5 days. This regimen was 

administered every three weeks for 4 cycles in case at least a minor response (≥ 25% reduction in 

bidimensionally measured tumour size) was observed after 2 cycles. At the end of chemotherapy, with 

a minimal interval of 4 weeks and a maximal interval of 7 weeks, patients whose disease did not 

progress received radiotherapy (RT) according to institutional guidelines for 7 weeks (TPF/RT). 

Patients on the comparator arm received cisplatin (P) 100 mg/m2 followed by 5-fluorouracil (F) 

1000 mg/m2 per day for 5 days. This regimen was administered every three weeks for 4 cycles in case 

at least a minor response (≥ 25% reduction in bidimensionally measured tumour size) was observed 

after 2 cycles. At the end of chemotherapy, with a minimal interval of 4 weeks and a maximal interval 

of 7 weeks, patients whose disease did not progress received radiotherapy (RT) according to 

institutional guidelines for 7 weeks (PF/RT). Locoregional therapy with radiation was delivered either 

with a conventional fraction (1.8 Gy - 2.0 Gy once a day, 5 days per week for a total dose of 66 to 

70 Gy), or accelerated/hyperfractionated regimens of radiation therapy (twice a day, with a minimum 

interfraction interval of 6 hours, 5 days per week). A total of 70 Gy was recommended for accelerated 

regimens and 74 Gy for hyperfractionated schemes. Surgical resection was allowed following 

chemotherapy, before or after radiotherapy. Patients on the TPF arm received antibiotic prophylaxis 

with ciprofloxacin 500 mg orally twice daily for 10 days starting on day 5 of each cycle, or equivalent. 

The primary endpoint in this study, progression-free survival (PFS), was significantly longer in the 

TPF arm compared to the PF arm, p = 0.0042 (median PFS: 11.4 vs. 8.3 months respectively) with an 

overall median follow up time of 33.7 months. Median overall survival was also significantly longer in 

favour of the TPF arm compared to the PF arm (median OS: 18.6 vs. 14.5 months respectively) with a 

28% risk reduction of mortality, p = 0.0128. Efficacy results are presented in the table below:  

 

Efficacy of docetaxel in the induction treatment of patients with inoperable locally advanced SCCHN 

(Intent-to-Treat Analysis) 

 

Endpoint Docetaxel + 

Cis + 5-FU 

n = 177 

Cis + 5-FU 

 

n = 181 

Median progression free survival (months) 

(95% CI) 

Adjusted Hazard ratio 

(95% CI) 

*p-value 

11.4 

(10.1-14.0) 

8.3 

(7.4-9.1) 

0.70 

(0.55-0.89) 

0.0042 

Median survival (months) 

(95% CI) 

18.6 

(15.7-24.0) 

14.5 

(11.6-18.7) 



41 

Endpoint Docetaxel + 

Cis + 5-FU 

n = 177 

Cis + 5-FU 

 

n = 181 

Hazard ratio 

(95% CI) 

**p-value 

0.72 

(0.56-0.93) 

0.0128 

Best overall response to chemotherapy (%) 

(95% CI)  

***p-value 

67.8 

(60.4-74.6) 

53.6 

(46.0-61.0) 

0.006 

Best overall response to study treatment [chemotherapy 

+/- radiotherapy] (%) 

(95% CI)  

***p-value 

72.3 

(65.1-78.8) 

58.6 

(51.0-65.8) 

0.006 

 Median duration of response to chemotherapy ± 

radiotherapy (months) 

(95% CI)  

Hazard ratio 

(95% CI) 

**p-value 

n = 128 

15.7 

(13.4-24.6) 

n = 106 

11.7 

(10.2-17.4) 

0.72 

(0.52-0.99) 

0.0457 

A hazard ratio of less than 1 favours docetaxel + cisplatin + 5-FU 

*Cox model (adjustment for Primary tumour site, T and N clinical stages and PSWHO) 

**Logrank test  

*** Chi-square test  

 

Quality of life parameters 

 

Patients treated with TPF experienced significantly less deterioration of their Global health score 

compared to those treated with PF (p = 0.01, using the EORTC QLQ-C30 scale). 

 

Clinical benefit parameters 

 

The performance status scale, for head and neck (PSS-HN) subscales designed to measure 

understandability of speech, ability to eat in public, and normalcy of diet, was significantly in favour 

of TPF as compared to PF. 

Median time to first deterioration of WHO performance status was significantly longer in the TPF arm 

compared to PF. Pain intensity score improved during treatment in both groups indicating adequate 

pain management.  

 

• Induction chemotherapy followed by chemoradiotherapy (TAX324)  
The safety and efficacy of docetaxel in the induction treatment of patients with locally advanced 

squamous cell carcinoma of the head and neck (SCCHN) was evaluated in a randomised, multi-centre 

open-label, phase III, study (TAX324). In this study, 501 patients, with locally advanced SCCHN, and 

a WHO performance status of 0 or 1, were randomised to one of two arms. The study population 

comprised patients with technically unresectable disease, patients with low probability of surgical cure 

and patients aiming at organ preservation. The efficacy and safety evaluation solely addressed survival 

endpoints and the success of organ preservation was not formally addressed. Patients on the docetaxel 

arm received docetaxel (T) 75 mg/m² by intravenous infusion on day 1 followed by cisplatin (P) 

100 mg/m² administered as a 30-minute to three-hour intravenous infusion, followed by the continuous 

intravenous infusion of 5-fluorouracil (F) 1000 mg/m²/day from day 1 to day 4. The cycles were 

repeated every 3 weeks for 3 cycles. All patients who did not have progressive disease were to receive 

chemoradiotherapy (CRT) as per protocol (TPF/CRT). Patients on the comparator arm received 

cisplatin (P) 100 mg/m² as a 30-minute to three-hour intravenous infusion on day 1 followed by the 

continuous intravenous infusion of 5-fluorouracil (F) 1000 mg/m²/day from day 1 to day 5. The cycles 



42 

were repeated every 3 weeks for 3 cycles. All patients who did not have progressive disease were to 

receive CRT as per protocol (PF/CRT).  

Patients in both treatment arms were to receive 7 weeks of CRT following induction chemotherapy 

with a minimum interval of 3 weeks and no later than 8 weeks after start of the last cycle (day 22 to 

day 56 of last cycle). During radiotherapy, carboplatin (AUC 1.5) was given weekly as a one-hour 

intravenous infusion for a maximum of 7 doses. Radiation was delivered with megavoltage equipment 

using once daily fractionation (2 Gy per day, 5 days per week for 7 weeks, for a total dose of 

70-72 Gy). Surgery on the primary site of disease and/or neck could be considered at anytime 

following completion of CRT. All patients on the docetaxel-containing arm of the study received 

prophylactic antibiotics. The primary efficacy endpoint in this study, overall survival (OS) was 

significantly longer (log-rank test, p = 0.0058) with the docetaxel-containing regimen compared to PF 

(median OS: 70.6 versus 30.1 months respectively), with a 30% risk reduction in mortality compared 

to PF (hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.54-0.90) with an overall median 

follow up time of 41.9 months. The secondary endpoint, PFS, demonstrated a 29% risk reduction of 

progression or death and a 22 month improvement in median PFS (35.5 months for TPF and 13.1 for 

PF). This was also statistically significant with an HR of 0.71; 95% CI 0.56-0.90; log-rank test 

p = 0.004. Efficacy results are presented in the table below: 

 

Efficacy of docetaxel in the induction treatment of patients with locally advanced SCCHN (Intent-to-

Treat Analysis) 

 

 

Endpoint Docetaxel + Cis + 5-FU 

n = 255 

Cis + 5-FU 

n = 246 

Median overall survival (months) 

(95% CI) 

Hazard ratio: 

(95% CI) 

*p-value  

70.6 

(49.0-NA) 

30.1 

(20.9-51.5) 

0.70 

(0.54-0.90) 

0.0058 

Median PFS (months) 

(95% CI) 

Hazard ratio: 

(95% CI) 

**p-value  

35.5 

(19.3-NA) 

13.1 

(10.6-20.2) 

0.71 

(0.56 - 0.90) 

0.004 

Best overall response (CR + PR) to 

chemotherapy (%) 

(95% CI)  

***p-value 

71.8 

(65.8-77.2) 

64.2 

(57.9-70.2) 

0.070 

Best overall response (CR + PR) to study 

treatment [chemotherapy +/- 

chemoradiotherapy] (%) 

(95% CI) 

***p-value 

 

76.5 

(70.8-81.5) 

 

71.5 

(65.5-77.1) 

0.209 

A hazard ratio of less than 1 favours docetaxel + cisplatin + fluorouracil  

*un-adjusted log-rank test  

**un-adjusted log-rank test, not adjusted for multiple comparisons  

***Chi square test, not adjusted for multiple comparisons  

NA-not applicable 

 

 

 

 

 



43 

5.2 Pharmacokinetic properties 

 

Absorption 

 

The pharmacokinetics of docetaxel have been evaluated in cancer patients after administration of 20-

115 mg/m2 in phase I studies. The kinetic profile of docetaxel is dose independent and consistent with 

a three-compartment pharmacokinetic model with half lives for the α, β and γ phases of 4 min, 36 min 

and 11.1 h, respectively. The late phase is due, in part, to a relatively slow efflux of docetaxel from the 

peripheral compartment. 

 

Distribution 

 

Following the administration of a 100 mg/m2 dose given as a one-hour infusion a mean peak plasma 

level of 3.7 μg/ml was obtained with a corresponding AUC of 4.6 h.μg/ml. Mean values for total body 

clearance and steady-state volume of distribution were 21 l/h/m2 and 113 l, respectively. Inter 

individual variation in total body clearance was approximately 50%. Docetaxel is more than 95% 

bound to plasma proteins.  

 

Elimination 

 

A study of 14C-docetaxel has been conducted in three cancer patients. Docetaxel was eliminated in 

both the urine and faeces following cytochrome P450-mediated oxidative metabolism of the tert-butyl 

ester group, within seven days, the urinary and faecal excretion accounted for about 6% and 75% of 

the administered radioactivity, respectively. About 80% of the radioactivity recovered in faeces is 

excreted during the first 48 hours as one major inactive metabolite and 3 minor inactive metabolites 

and very low amounts of unchanged medicinal product. 

Special populations 

 

Age and gender 

 

A population pharmacokinetic analysis has been performed with docetaxel in 577 patients. 

Pharmacokinetic parameters estimated by the model were very close to those estimated from phase I 

studies. The pharmacokinetics of docetaxel were not altered by the age or sex of the patient. 

 

Hepatic impairment 

In a small number of patients (n = 23) with clinical chemistry data suggestive of mild to moderate liver 

function impairment (ALT, AST ≥ 1.5 times the ULN associated with alkaline phosphatase ≥ 2.5 

times the ULN), total clearance was lowered by 27% on average (see section 4.2). 

 

Fluid retention 

Docetaxel clearance was not modified in patients with mild to moderate fluid retention and there are 

no data available in patients with severe fluid retention. 

 

Combination therapy 

 

Doxorubicin 

When used in combination, docetaxel does not influence the clearance of doxorubicin and the plasma 

levels of doxorubicinol (a doxorubicin metabolite). The pharmacokinetics of docetaxel, doxorubicin 

and cyclophosphamide were not influenced by their co-administration.  

 

Capecitabine 

Phase I study evaluating the effect of capecitabine on the pharmacokinetics of docetaxel and vice versa 

showed no effect by capecitabine on the pharmacokinetics of docetaxel (Cmax and AUC) and no 

effect by docetaxel on the pharmacokinetics of a relevant capecitabine metabolite 5'-DFUR.  

 

 

 



44 

Cisplatin 

Clearance of docetaxel in combination therapy with cisplatin was similar to that observed following 

monotherapy. The pharmacokinetic profile of cisplatin administered shortly after docetaxel infusion is 

similar to that observed with cisplatin alone.  

 

Cisplatin and 5-fluorouracil 

The combined administration of docetaxel, cisplatin and 5-fluorouracil in 12 patients with solid 

tumours had no influence on the pharmacokinetics of each individual medicinal product.  

 

Prednisone and dexamethasone 

The effect of prednisone on the pharmacokinetics of docetaxel administered with standard 

dexamethasone premedication has been studied in 42 patients. 

 

Prednisone 

No effect of prednisone on the pharmacokinetics of docetaxel was observed. 

 

 

5.3  Preclinical safety data 

 

The carcinogenic potential of docetaxel has not been studied. 

 

Docetaxel has been shown to be mutagenic in the in vitro micronucleus and chromosome aberration 

test in CHO-K1 cells and in the in vivo micronucleus test in the mouse. However, it did not induce 

mutagenicity in the Ames test or the CHO/HGPRT gene mutation assay. These results are consistent 

with the pharmacological activity of docetaxel.  

 

It was shown that docetaxel was embryotoxic and fetotoxic in rats and rabbits. Undesirable effects on 

the testis observed in rodent toxicity studies suggest that docetaxel may impair male fertility. 

 

 

6. PHARMACEUTICAL PARTICULARS 
 

6.1 List of excipients 

 

Polysorbate 80 

Ethanol anhydrous 

Anhydrous citric acid (pH adjustment) 

 

 

6.2 Incompatibilities 

 

This medicinal product must not be mixed with other medicinal products except those mentioned in 

section 6.6. 

 

 

6.3 Shelf life 

 

Unopened vial 

2 years. 

 

After opening of the vial 

Each vial is for single use and should be used immediately after opening. If not used immediately, 

in-use storage times and conditions are the responsibility of the user. 

 

Once added to the infusion bag 



45 

From a microbiological point of view, reconstitution/dilution must take place in controlled and aseptic 

conditions and the medicinal product should be used immediately. If not used immediately, in-use 

storage times and conditions are the responsibility of the user. 

 

Once added as recommended into the infusion bag, the docetaxel infusion solution, if stored below 

25°C, is stable for 6 hours. It should be used within 6 hours (including the one hour infusion 

intravenous administration). 

 

In addition, physical and chemical in-use stability of the infusion solution prepared as recommended 

has been demonstrated in non-PVC bags up to 48 hours when stored between 2 to 8°C. 

 

 

6.4 Special precautions for storage 

 

Do not store above 25°C.  

Store in the original package in order to protect from light.  

 

For storage conditions of the diluted medicinal product, see section 6.3. 

 

 

6.5 Nature and contents of container 

 

6 ml clear, colourless Type-I glass vial, closed with flurotec rubber stopper and a green flip-off 

aluminium over seal containing 1 ml of concentrate. 

 

Each box contains one vial. 

 

 

6.6 Special precautions for disposal and other handling 

 

DOCETAXEL KABI is an antineoplastic agent and, as with other potentially toxic compounds, 

caution should be exercised when handling it and preparing the solution. The use of gloves is 

recommended. 

 

If DOCETAXEL KABI concentrate or infusion solution should come into contact with skin, wash 

immediately and thoroughly with soap and water. If DOCETAXEL KABI concentrate or infusion 

solution should come into contact with mucous membranes, wash immediately and thoroughly with 

water. 

 

Preparation for the intravenous administration 

 

Preparation of the infusion solution 

DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 

with this medicinal product (DOCETAXEL KABI 20 mg/1 ml concentrate for solution for 

infusion, which contains only 1 vial). 

 

DOCETAXEL KABI 20 mg/1 ml concentrate for solution for infusion requires NO prior 

dilution with a solvent and is ready to add to the infusion solution. 

 

Each vial is for single use and should be used immediately. 

 

If the vials are stored under refrigeration, allow the required number of boxes of DOCETAXEL KABI 

concentrate for solution for infusion to stand below 25°C for 5 minutes before use. More than one vial 

of DOCETAXEL KABI concentrate for solution for infusion may be necessary to obtain the required 

dose for the patient. Aseptically withdraw the required amount of DOCETAXEL KABI concentrate 

for solution for infusion using a calibrated syringe.  

 



46 

In DOCETAXEL KABI 20 mg/1 ml vial the concentration of docetaxel is 20 mg/ml. 

The required volume of DOCETAXEL KABI concentrate for solution for infusion must be injected 

via a single injection (one shot) into a 250 ml infusion bag or bottle containing either 5% glucose 

solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. 

 

If a dose greater than 190 mg of docetaxel is required, use a larger volume of the infusion vehicle so 

that a concentration of 0.74 mg/ml docetaxel is not exceeded. 

 

Mix the infusion bag or bottle manually using a rocking motion. 

 

The infusion bag solution should be used within 6 hours below 25°C including the one hour infusion 

to the patient. 

 

As with all parenteral products, DOCETAXEL KABI infusion solution should be visually inspected 

prior to use, and solutions containing a precipitate should be discarded. 

 

Docetaxel infusion solution is supersaturated, therefore may crystallize over time. If crystals appear, 

the solution must no longer be used and shall be discarded. 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

 

Fresenius Kabi Deutschland GmbH 

Else-Kröner-Straße 1, 

61352 Bad Homburg v.d.Höhe 

Germany 

 

 

8. MARKETING AUTHORISATION NUMBER 
 

EU/1/12/770/005 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 22nd May 2012 

Date of latest renewal: 23 February 2017  

 

 

10. DATE OF REVISION OF THE TEXT 
 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu  



47 

 

1. NAME OF THE MEDICINAL PRODUCT 
 

DOCETAXEL KABI 80 mg/4 ml concentrate for solution for infusion 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each ml of concentrate contains 20 mg docetaxel anhydrous. 

 

One vial of 4 ml of concentrate contains 80 mg of docetaxel. 

 

Excipient with known effect 

Each vial of concentrate contains 2 ml of ethanol anhydrous (1.58 g). 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Concentrate for solution for infusion (sterile concentrate). 

 

The concentrate is a clear, colourless to pale yellow solution. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 

 

Breast cancer 

 

DOCETAXEL KABI in combination with doxorubicin and cyclophosphamide is indicated for the 

adjuvant treatment of patients with: 

• operable node-positive breast cancer 

• operable node-negative breast cancer. 
 

For patients with operable node-negative breast cancer, adjuvant treatment should be restricted to 

patients eligible to receive chemotherapy according to internationally established criteria for primary 

therapy of early breast cancer (see section 5.1). 

DOCETAXEL KABI in combination with doxorubicin is indicated for the treatment of patients with 

locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for 

this condition. 

 

DOCETAXEL KABI monotherapy is indicated for the treatment of patients with locally advanced or 

metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have 

included an anthracycline or an alkylating agent. 

 

DOCETAXEL KABI in combination with trastuzumab is indicated for the treatment of patients with 

metastatic breast cancer whose tumours over express HER2 and who previously have not received 

chemotherapy for metastatic disease. 

 

DOCETAXEL KABI in combination with capecitabine is indicated for the treatment of patients with 

locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy 

should have included an anthracycline. 



48 

Non-small cell lung cancer 
 

DOCETAXEL KABI is indicated for the treatment of patients with locally advanced or metastatic 

non-small cell lung cancer after failure of prior chemotherapy. 

 

DOCETAXEL KABI in combination with cisplatin is indicated for the treatment of patients with 

unresectable, locally advanced or metastatic non-small cell lung cancer, in patients who have not 

previously received chemotherapy for this condition. 

 

Prostate cancer 

 

DOCETAXEL KABI in combination with prednisone or prednisolone is indicated for the treatment of 

patients with castration-resistant metastatic prostate cancer. 

 

DOCETAXEL KABI in combination with androgen-deprivation therapy (ADT), with or without 

prednisone or prednisolone, is indicated for the treatment of patients with metastatic hormone-

sensitive prostate cancer. 

 

Gastric adenocarcinoma 

 

DOCETAXEL KABI in combination with cisplatin and 5-fluorouracil is indicated for the treatment of 

patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal 

junction, who have not received prior chemotherapy for metastatic disease. 

 

Head and neck cancer 

 

DOCETAXEL KABI in combination with cisplatin and 5-fluorouracil is indicated for the induction 

treatment of patients with locally advanced squamous cell carcinoma of the head and neck. 

 

 

4.2 Posology and method of administration 

 

The use of docetaxel should be confined to units specialised in the administration of cytotoxic 

chemotherapy and it should only be administered under the supervision of a physician qualified in the 

use of anticancer chemotherapy (see section 6.6). 

 

Posology 

For breast, non-small cell lung, gastric, and head and neck cancers, premedication consisting of an oral 

corticosteroid, such as dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to 

docetaxel administration, unless contraindicated, can be used (see section 4.4).  

For metastatic castration-resistant prostate cancer, given the concurrent use of prednisone or 

prednisolone the recommended premedication regimen is oral dexamethasone 8 mg, 12 hours, 3 hours 

and 1 hour before the docetaxel infusion (see section 4.4). 

For metastatic hormone-sensitive prostate cancer, irrespective of the concurrent use of prednisone or 

prednisolone, the recommended premedication regimen is oral dexamethasone 8 mg 12 hours, 3 hours, 

and 1 hour before docetaxel infusion (see section 4.4). 

Prophylactic G-CSF may be used to mitigate the risk of haematological toxicities. 

 

Docetaxel is administered as a one-hour infusion every three weeks.  

 

Breast cancer 

In the adjuvant treatment of operable node-positive and node-negative breast cancer, the recommended 

dose of docetaxel is 75 mg/m2 administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 

500 mg/m2 every 3 weeks for 6 cycles (TAC regimen) (see also Dose adjustments during treatment). 

For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose 

of docetaxel is 100 mg/m2 in monotherapy. In first-line treatment, docetaxel 75 mg/m2 is given in 

combination therapy with doxorubicin (50 mg/m2). 



49 

 

In combination with trastuzumab the recommended dose of docetaxel is 100 mg/m2 every three weeks, 

with trastuzumab administered weekly. In the pivotal study the initial docetaxel infusion was started 

the day following the first dose of trastuzumab. The subsequent docetaxel doses were administered 

immediately after completion of the trastuzumab infusion, if the preceding dose of trastuzumab was 

well tolerated. For trastuzumab dose and administration, see trastuzumab summary of product 

characteristics.  

 

In combination with capecitabine, the recommended dose of docetaxel is 75 mg/m2 every three weeks, 

combined with capecitabine at 1250 mg/m2 twice daily (within 30 minutes after a meal) for 2 weeks 

followed by 1-week rest period. For capecitabine dose calculation according to body surface area, see 

capecitabine summary of product characteristics.  

 

Non-small cell lung cancer 

In chemotherapy naïve patients treated for non-small cell lung cancer, the recommended dose regimen 

is docetaxel 75 mg/m2 immediately followed by cisplatin 75 mg/m2 over 30-60 minutes. For treatment 

after failure of prior platinum-based chemotherapy, the recommended dose is 75 mg/m² as a single 

agent. 

 

Prostate cancer 

Prostate cancer Metastatic castration-resistant prostate cancer  
The recommended dose of docetaxel is 75 mg/m2. Prednisone or prednisolone 5 mg orally twice daily 

is administered continuously (see section 5.1). 

 

Metastatic hormone-sensitive prostate cancer 

The recommended dose of docetaxel is 75 mg/m2 every 3 weeks for 6 cycles. Prednisone or 

prednisolone 5 mg orally twice daily may be administered continuously. 

 

Gastric adenocarcinoma 

The recommended dose of docetaxel is 75 mg/m2 as a 1-hour infusion, followed by cisplatin 

75 mg/m2, as a 1- to 3- hour infusion (both on day 1 only), followed by 5-fluorouracil 750 mg/m2 per 

day given as a 24-hour continuous infusion for 5 days, starting at the end of the cisplatin infusion. 

Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and 

appropriate hydration for cisplatin administration. Prophylactic G-CSF should be used to mitigate the 

risk of haematological toxicities (see also Dose adjustments during treatment). 

 

Head and neck cancer 

Patients must receive premedication with antiemetics and appropriate hydration (prior to and after 

cisplatin administration). Prophylactic G-CSF may be used to mitigate the risk of haematological 

toxicities. All patients on the docetaxel-containing arm of the TAX 323 and TAX 324 studies, received 

prophylactic antibiotics. 

 

• Induction chemotherapy followed by radiotherapy (TAX 323) 
For the induction treatment of inoperable locally advanced squamous cell carcinoma of the head 

and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m2 as a 1 hour infusion 

followed by cisplatin 75 mg/m2 over 1 hour, on day one, followed by 5-fluorouracil as a 

continuous infusion at 750 mg/m2 per day for five days. This regimen is administered every 

3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy. 

 

• Induction chemotherapy followed by chemoradiotherapy (TAX 324) 
For the induction treatment of patients with locally advanced (technically unresectable, low 

probability of surgical cure, and aiming at organ preservation) squamous cell carcinoma of the 

head and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m2 as a 1 hour 

intravenous infusion on day 1, followed by cisplatin 100 mg/m2 administered as a 30-minute to 

3-hour infusion, followed by 5-fluorouracil 1000 mg/m2/day as a continuous infusion from day 1 

to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, 

patients should receive chemoradiotherapy. 



50 

 

For cisplatin and 5-fluorouracil dose modifications, see the corresponding summary of product 

characteristics. 

 

Dose adjustments during treatment 

 

General 

Docetaxel should be administered when the neutrophil count is ≥ 1,500 cells/mm3. 

In patients who experienced either febrile neutropenia, neutrophil count < 500 cells/mm3 for more than 

one week, severe or cumulative cutaneous reactions or severe peripheral neuropathy during docetaxel 

therapy, the dose of docetaxel should be reduced from 100 mg/m2 to 75 mg/m2 and/or from 75 to 

60 mg/m². If the patient continues to experience these reactions at 60 mg/m², the treatment should be 

discontinued. 

 

Adjuvant therapy for breast cancer 

Primary G-CSF prophylaxis should be considered in patients who receive docetaxel, doxorubicin and 

cyclophosphamide (TAC) adjuvant therapy for breast cancer. Patients who experience febrile 

neutropenia and/or neutropenic infection should have their docetaxel dose reduced to 60 mg/m² in all 

subsequent cycles (see sections 4.4 and 4.8). Patients who experience Grade 3 or 4 stomatitis should 

have their dose decreased to 60 mg/m². 

 

In combination with cisplatin 

For patients who are dosed initially at docetaxel 75 mg/m2 in combination with cisplatin and whose 

nadir of platelet count during the previous course of therapy is < 25,000 cells/mm3, or in patients who 

experience febrile neutropenia, or in patients with serious non-haematologic toxicities, the docetaxel 

dose in subsequent cycles should be reduced to 65 mg/m2. For cisplatin dose adjustments, see the 

corresponding summary of product characteristics.  

 

In combination with capecitabine 

• For capecitabine dose modifications, see capecitabine summary of product characteristics. 

• For patients developing the first appearance of Grade 2 toxicity, which persists at the time of the 
next docetaxel/capecitabine treatment, delay treatment until resolved to Grade 0-1, and resume at 

100% of the original dose. 

• For patients developing the second appearance of Grade 2 toxicity, or the first appearance of 
Grade 3 toxicity, at any time during the treatment cycle, delay treatment until resolved to Grade 

0-1 and then resume treatment with docetaxel 55 mg/m². 

• For any subsequent appearances of toxicities, or any Grade 4 toxicities, discontinue the docetaxel 
dose. 

 

For trastuzumab dose modifications, see trastuzumab summary of product characteristics. 

 

In combination with cisplatin and 5-fluorouracil 

If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite 

G-CSF use, the docetaxel dose should be reduced from 75 to 60 mg/m2. If subsequent episodes of 

complicated neutropenia occur the docetaxel dose should be reduced from 60 to 45 mg/m2. In case of 

Grade 4 thrombocytopenia the docetaxel dose should be reduced from 75 to 60 mg/m2. Patients should 

not be retreated with subsequent cycles of docetaxel until neutrophils recover to a level 

>1,500 cells/mm3 and platelets recover to a level >100,000 cells/mm3. Discontinue treatment if these 

toxicities persist (see section 4.4). 

Recommended dose modifications for toxicities in patients treated with docetaxel in combination with 

cisplatin and 5-fluorouracil (5-FU): 

 

Toxicity Dose adjustment 

Diarrhoea grade 3  First episode: reduce 5-FU dose by 20%. 

Second episode: then reduce docetaxel dose by 20%. 



51 

Toxicity Dose adjustment 

Diarrhoea grade 4 First episode: reduce docetaxel and 5-FU doses by 20%. 

Second episode: discontinue treatment. 

Stomatitis/mucositis grade 3  First episode: reduce 5-FU dose by 20%. 

Second episode: stop 5-FU only, at all subsequent cycles. 

Third episode: reduce docetaxel dose by 20%. 

Stomatitis/mucositis grade 4 First episode: stop 5-FU only, at all subsequent cycles. 

Second episode: reduce docetaxel dose by 20%. 

 

For cisplatin and 5-fluorouracil dose adjustments, see the corresponding summary of product 

characteristics. 

 

In the pivotal SCCHN studies patients who experienced complicated neutropenia (including prolonged 

neutropenia, febrile neutropenia, or infection), it was recommended to use G-CSF to provide 

prophylactic coverage (eg, day 6-15) in all subsequent cycles. 

 

Special populations 

 

Patients with hepatic impairment 

Based on pharmacokinetic data with docetaxel at 100 mg/m² as single agent, patients who have both 

elevations of transaminase (ALT and/or AST) greater than 1.5 times the upper limit of the normal 

range (ULN) and alkaline phosphatase greater than 2.5 times the ULN, the recommended dose of 

docetaxel is 75 mg/m2 (see sections 4.4 and 5.2). For those patients with serum bilirubin > ULN and/or 

ALT and AST > 3.5 times the ULN associated with alkaline phosphatase > 6 times the ULN, no 

dose-reduction can be recommended and docetaxel should not be used unless strictly indicated. 

In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric 

adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST > 1.5 × ULN 

associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no 

dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No 

data are available in patients with hepatic impairment treated by docetaxel in combination in the other 

indications.  

 

Paediatric population 

The safety and efficacy of DOCETAXEL KABI in nasopharyngeal carcinoma in children aged 

1 month to less than 18 years have not yet been established. 

There is no relevant use of DOCETAXEL KABI in the paediatric population in the indications breast 

cancer, non-small cell lung cancer, prostate cancer, gastric carcinoma and head and neck cancer, not 

including type II and III less differentiated nasopharyngeal carcinoma. 

 

Elderly  

Based on a population pharmacokinetic analysis, there are no special instructions for use in the elderly. 

In combination with capecitabine, for patients 60 years of age or more, a starting dose reduction of 

capecitabine to 75% is recommended (see capecitabine summary of product characteristics). 

 

Method of administration 

For instructions on preparation and administration of the product, see section 6.6. 

 

 

4.3 Contraindications 

 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 

Patients with baseline neutrophil count of < 1,500 cells/mm3. 

 



52 

Patients with severe liver impairment (see sections 4.2 and 4.4). 

 

Contraindications for other medicinal products also apply, when combined with docetaxel. 

 

 

4.4 Special warnings and precautions for use 

 

For breast and non-small cell lung cancers, premedication consisting of an oral corticosteroid, such as 

dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to docetaxel 

administration, unless contraindicated, can reduce the incidence and severity of fluid retention as well 

as the severity of hypersensitivity reactions. For prostate cancer, the premedication is oral 

dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the docetaxel infusion (see section 4.2). 

 

Haematology 

 

Neutropenia is the most frequent adverse reaction of docetaxel. Neutrophil nadirs occurred at a median 

of 7 days but this interval may be shorter in heavily pre-treated patients. Frequent monitoring of 

complete blood counts should be conducted on all patients receiving docetaxel. Patients should be 

retreated with docetaxel when neutrophils recover to a level ≥ 1,500 cells/mm3 (see section 4.2). 

 

In the case of severe neutropenia (< 500 cells/mm3 for seven days or more) during a course of 

docetaxel therapy, a reduction in dose for subsequent courses of therapy or the use of appropriate 

symptomatic measures are recommended (see section 4.2). 

 

In patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (TCF), febrile 

neutropenia and neutropenic infection occurred at lower rates when patients received prophylactic 

G-CSF. Patients treated with TCF should receive prophylactic G-CSF to mitigate the risk of 

complicated neutropenia (febrile neutropenia, prolonged neutropenia or neutropenic infection). 

Patients receiving TCF should be closely monitored (see sections 4.2 and 4.8). 

 

In patients treated with docetaxel in combination with doxorubicin and cyclophosphamide (TAC), 

febrile neutropenia and/or neutropenic infection occurred at lower rates when patients received 

primary G-CSF prophylaxis. Primary G-CSF prophylaxis should be considered in patients who receive 

adjuvant therapy with TAC for breast cancer to mitigate the risk of complicated neutropenia (febrile 

neutropenia, prolonged neutropenia or neutropenic infection). Patients receiving TAC should be 

closely monitored (see sections 4.2 and 4.8). 

 

Gastrointestinal reactions 

 

Caution is recommended for patients with neutropenia, particularly at risk for developing 

gastrointestinal complications. Although majority of cases occurred during the first or second cycle of 

docetaxel containing regimen, enterocolitis could develop at any time, and could lead to death as early 

as on the first day of onset. Patients should be closely monitored for early manifestations of serious 

gastrointestinal toxicity (see sections 4.2, 4.4 Haematology, and 4.8). 

 

Hypersensitivity reactions 

 

Patients should be observed closely for hypersensitivity reactions especially during the first and 

second infusions. Hypersensitivity reactions may occur within a few minutes following the initiation 

of the infusion of docetaxel, thus facilities for the treatment of hypotension and bronchospasm should 

be available. If hypersensitivity reactions occur, minor symptoms such as flushing or localised 

cutaneous reactions do not require interruption of therapy. However, severe reactions, such as severe 

hypotension, bronchospasm or generalised rash/erythema require immediate discontinuation of 

docetaxel and appropriate therapy. Patients who have developed severe hypersensitivity reactions 

should not be re-challenged with docetaxel. Patients who have previously experienced a 

hypersensitivity reaction to paclitaxel may be at risk to develop hypersensitivity reaction to docetaxel, 



53 

including more severe hypersensitivity reaction. These patients should be closely monitored during 

initiation of docetaxel therapy. 

 

Cutaneous reactions 

 

Localised skin erythema of the extremities (palms of the hands and soles of the feet) with oedema 

followed by desquamation has been observed. Severe symptoms such as eruptions followed by 

desquamation which lead to interruption or discontinuation of docetaxel treatment were reported (see 

section 4.2). 

 

Severe Cutaneous Adverse Reactions (SCARs) such as Stevens-Johnson Syndrome (SJS), Toxic 

Epidermal Necrolysis (TEN) and Acute Generalized Exanthematous Pustulosis (AGEP) have been 

reported with docetaxel treatment. Patients should be informed about the signs and symptoms of 

serious skin manifestations and closely monitored. If signs and symptoms suggestive of these reactions 

appear discontinuation of docetaxel should be considered. 

 

Fluid retention 

 

Patients with severe fluid retention such as pleural effusion, pericardial effusion and ascites should be 

monitored closely. 

 

Respiratory disorders 

 

Acute respiratory distress syndrome, interstitial pneumonia/pneumonitis, interstitial lung disease, 

pulmonary fibrosis and respiratory failure have been reported and may be associated with fatal 

outcome. Cases of radiation pneumonitis have been reported in patients receiving concomitant 

radiotherapy. 

 

If new or worsening pulmonary symptoms develop, patients should be closely monitored, promptly 

investigated, and appropriately treated. Interruption of docetaxel therapy is recommended until 

diagnosis is available. Early use of supportive care measures may help improve the condition. The 

benefit of resuming docetaxel treatment must be carefully evaluated. 

 

Patients with liver impairment 

 

In patients treated with docetaxel at 100 mg/m2 as single agent who have serum transaminase levels 

(ALT and/or AST) greater than 1.5 times the ULN concurrent with serum alkaline phosphatase levels 

greater than 2.5 times the ULN, there is a higher risk of developing severe adverse reactions such as 

toxic deaths including sepsis and gastrointestinal haemorrhage which can be fatal, febrile neutropenia, 

infections, thrombocytopenia, stomatitis and asthenia. Therefore, the recommended dose of docetaxel 

in those patients with elevated liver function test (LFTs) is 75 mg/m2 and LFTs should be measured at 

baseline and before each cycle (see section 4.2). 

For patients with serum bilirubin levels > ULN and/or ALT and AST > 3.5 times the ULN concurrent 

with serum alkaline phosphatase levels > 6 times the ULN, no dose-reduction can be recommended 

and docetaxel should not be used unless strictly indicated. 

In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric 

adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST > 1.5 × ULN 

associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no 

dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No 

data are available in patients with hepatic impairment treated by docetaxel in combination in the other 

indications.  

 

Patients with renal impairment 

 

There are no data available in patients with severely impaired renal function treated with docetaxel. 

 

 



54 

Nervous system 

The development of severe peripheral neurotoxicity requires a reduction of dose (see section 4.2). 

 

Cardiac toxicity 

 

Heart failure has been observed in patients receiving docetaxel in combination with trastuzumab, 

particularly following anthracycline (doxorubicin or epirubicin)-containing chemotherapy. This may 

be moderate to severe and has been associated with death (see section 4.8). 

 

When patients are candidates for treatment with docetaxel in combination with trastuzumab, they 

should undergo baseline cardiac assessment. Cardiac function should be further monitored during 

treatment (e.g. every three months) to help identify patients who may develop cardiac dysfunction. For 

more details see summary of product characteristics of trastuzumab.  

 

Ventricular arrhythmia including ventricular tachycardia (sometimes fatal) has been reported in 

patients treated with docetaxel in combination regimens including doxorubicin, 5-fluorouracil and/ or 

cyclophosphamide (see section 4.8).  

Baseline cardiac assessment is recommended.   

 

Eye disorders 
 

Cystoid macular oedema (CMO) has been reported in patients treated with docetaxel. Patients with 

impaired vision should undergo a prompt and complete ophthalmologic examination. In case CMO is 

diagnosed, docetaxel treatment should be discontinued and appropriate treatment initiated (see section 

4.8). 

 

Second primary malignancies 

 

Second primary malignancies have been reported when docetaxel was given in combination with 

anticancer treatments known to be associated with second primary malignancies.  Second primary 

malignancies (including acute myeloid leukemia, myelodysplastic syndrome and non-Hodgkin 

lymphoma) may occur several months or years after docetaxel-containing therapy. Patients should be 

monitored for second primary malignancies (see section 4.8). 

 

Others 

 

Contraceptive measures must be taken by both men and women during treatment and for men at least 

6 months after cessation of therapy (see section 4.6). 

 

The concomitant use of docetaxel with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, 

clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and 

voriconazole) should be avoided (see section 4.5). 

 

Additional cautions for use in adjuvant treatment of breast cancer 

 

Complicated neutropenia 

For patients who experience complicated neutropenia (prolonged neutropenia, febrile neutropenia or 

infection), G-CSF and dose reduction should be considered (see section 4.2). 

 

Gastrointestinal reactions 

Symptoms such as early abdominal pain and tenderness, fever, diarrhoea, with or without neutropenia, 

may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated 

promptly. 

 

Congestive heart failure (CHF) 



55 

Patients should be monitored for symptoms of congestive heart failure during therapy and during the 

follow up period. In patients treated with the TAC regimen for node positive breast cancer, the risk of 

CHF has been shown to be higher during the first year after treatment (see sections 4.8 and 5.1). 

 

Patients with 4+ nodes 

As the benefit observed in patient with 4+ nodes was not statistically significant on disease-free 

survival (DFS) and overall survival (OS), the positive benefit/risk ratio for TAC in patients with 4+ 

nodes was not fully demonstrated at the final analysis (see section 5.1). 

 

Elderly  

Cautions for use in adjuvant treatment of breast cancer 

There are limited data available in patients > 70 years of age on docetaxel use in combination with 

doxorubicin and cyclophosphamide. 

 

Cautions for use in castration-resistant prostate cancer 

Of the 333 patients treated with docetaxel every three weeks in a prostate cancer study, 209 patients 

were 65 years of age or greater and 68 patients were older than 75 years. In patients treated with 

docetaxel every three weeks, the incidence of related nail changes occurred at a rate ≥ 10% higher in 

patients who were 65 years of age or greater compared to younger patients. The incidence of related 

fever, diarrhoea, anorexia, and peripheral oedema occurred at rates ≥ 10% higher in patients who were 

75 years of age or greater versus less than 65 years. 

 

Cautions for use in hormone-sensitive prostate cancer 

Of the 545 patients treated with docetaxel every 3 weeks in a hormone-sensitive prostate cancer study 

(STAMPEDE), 296 patients were 65 years of age or older, and 48 patients were 75 years of age or 

older. More patients aged ≥65 years in the docetaxel arm reported hypersensitivity reaction, 

neutropenia, anaemia, fluid retention, dyspnea, and nail changes when compared to the patients aged 

less than 65 years. None of these increases in frequency reached 10% difference with the control arm. 

In patients who were 75 years of age or older, when compared to younger patients, neutropenia, 

anaemia, diarrhea, dyspnea and upper respiratory tract infection were reported with a greater incidence 

(at least 10% higher).  

 

Cautions for use in gastric adenocarcinoma cancer 

Among the 300 (221 patients in the phase III part of the study and 79 patients in the phase II part) 

patients treated with docetaxel in combination with cisplatin and 5-fluorouracil in the gastric cancer 

study, 74 were 65 years of age or older and 4 patients were 75 years of age or older. The incidence of 

serious adverse events was higher in older people compared to younger patients. The incidence of the 

following adverse events (all grades): lethargy, stomatitis, neutropenic infection occurred at rates 

≥ 10% higher in patients who were 65 years of age or older compared to younger patients. 

Elderly treated with TCF should be closely monitored. 

 

Excipients 

 
This medicinal product contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 1.58 g ethanol 

anhydrous per vial, equivalent to 40 ml of beer or 17 ml wine. 

Harmful for those suffering from alcoholism. 

To be taken into account in pregnant or breast-feeding women, children and high-risk groups 

such as patients with liver disease, or epilepsy. 
 

Consideration should be given to possible effects on the central nervous system. 

 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

The amount of alcohol in this medicinal product may alter the effects of other medicinal products. 



56 

In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant 

administration of compounds which induce, inhibit or are metabolised by (and thus may inhibit the 

enzyme competitively) cytochrome P450-3A such as ciclosporine, ketoconazole and erythromycin. As 

a result, caution should be exercised when treating patients with these medicinal products as 

concomitant therapy since there is a potential for a significant interaction. 

In case of combination with CYP3A4 inhibitors, the occurrence of docetaxel adverse reactions may 

increase, as a result of reduced metabolism. If the concomitant use of a strong CYP3A4 inhibitor (e.g., 

ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, 

telithromycin and voriconazole) cannot be avoided, a close clinical surveillance is warranted and a 

dose-adjustment of docetaxel may be suitable during the treatment with the strong CYP3A4 inhibitor 

(see section 4.4). In a pharmacokinetic study with 7 patients, the co-administration of docetaxel with 

the strong CYP3A4 inhibitor ketoconazole leads to a significant decrease in docetaxel clearance by 

49%. 

Docetaxel pharmacokinetics in the presence of prednisone was studied in patients with metastatic 

prostate cancer. Docetaxel is metabolised by CYP3A4 and prednisone is known to induce CYP3A4. 

No statistically significant effect of prednisone on the pharmacokinetics of docetaxel was observed. 

 

Docetaxel is highly protein bound (> 95%). Although the possible in vivo interaction of docetaxel with 

concomitantly administered medicinal product has not been investigated formally, in vitro interactions 

with tightly protein-bound agents such as erythromycin, diphenhydramine, propranolol, propafenone, 

phenytoin, salicylate, sulfamethoxazole and sodium valproate did not affect protein binding of 

docetaxel. In addition, dexamethasone did not affect protein binding of docetaxel. Docetaxel did not 

influence the binding of digitoxin. 

 

The pharmacokinetics of docetaxel, doxorubicin and cyclophosphamide were not influenced by their 

co-administration. Limited data from a single uncontrolled study were suggestive of an interaction 

between docetaxel and carboplatin. When combined to docetaxel, the clearance of carboplatin was 

about 50% higher than values previously reported for carboplatin monotherapy. 

 

 

4.6 Fertility, pregnancy and lactation 

 

Women of childbearing potential/ Contraception in males and females 

 

Women of childbearing age receiving docetaxel should be advised to avoid becoming pregnant, and to 

inform the treating physician immediately should this occur. An effective method of contraception 

should be used during treatment. 

 

Pregnancy 

 

There is no information on the use of docetaxel in pregnant women. Docetaxel has been shown to be 

both embryotoxic and foetotoxic in rabbits and rats, and to reduce fertility in rats (see section 5.3). As 

with other cytotoxic medicinal products, docetaxel may cause foetal harm when administered to 

pregnant women. Therefore, docetaxel must not be used during pregnancy unless clearly indicated.  

 

Breast-feeding 

 

Docetaxel is a lipophilic substance but it is not known whether it is excreted in human milk. 

Consequently, because of the potential for adverse reactions in nursing infants, breast feeding must be 

discontinued for the duration of docetaxel therapy. 

 

 

 

 

 



57 

Fertility 

 

In non clinical studies, docetaxel has genotoxic effects and may alter male fertility (see section 5.3). 

Therefore, men being treated with docetaxel are advised not to father a child during and up to 

6 months after treatment and to seek advice on conservation of sperm prior to treatment. 

 

 

4.7 Effects on ability to drive and use machines 

 

No studies on the effects on the ability to drive and use machines have been performed. The amount of 

alcohol in this medicinal product and the side effects of the product may impair the ability to drive or 

use machines (see sections 4.4 and 4.8). Therefore, patients should be warned of the potential impact 

of the amount of alcohol and the side effects of this medicinal product on the ability to drive or use 

machines, and be advised not to drive or use machines if they experience these side effects during 

treatment. 

 

 

4.8 Undesirable effects 

 

Summary of the safety profile for all indications 

 

The adverse reactions considered to be possibly or probably related to the administration of docetaxel 

have been obtained in: 

 

• 1,312 and 121 patients who received 100 mg/m² and 75 mg/m² of docetaxel as a single agent 
respectively. 

• 258 patients who received docetaxel in combination with doxorubicin. 

• 406 patients who received docetaxel in combination with cisplatin. 

• 92 patients treated with docetaxel in combination with trastuzumab. 

• 255 patients who received docetaxel in combination with capecitabine. 

• 332 patients (TAX327) who received docetaxel in combination with prednisone or prednisolone 
(clinically important treatment related adverse events are presented). 

• 1,276 patients (744 and 532 in TAX 316 and GEICAM 9805 respectively) who received 
docetaxel in combination with doxorubicin and cyclophosphamide (clinically important 

treatment related adverse events are presented). 

• 300 gastric adenocarcinoma patients (221 patients in the phase III part of the study and 
79 patients in the phase II part) who received docetaxel in combination with cisplatin and 

5-fluorouracil (clinically important treatment related adverse events are presented). 

• 174 and 251 head and neck cancer patients who received docetaxel in combination with 
cisplatin and 5-fluorouracil (clinically important treatment related adverse events are presented). 

• 545 patients (STAMPEDE study) who received docetaxel in combination with prednisone or 
prednisolone and ADT. 

 

These reactions were described using the NCI Common Toxicity Criteria (grade 3 = G3; 

grade 3-4 = G3/4; grade 4 = G4), the COSTART and the MedDRA terms. Frequencies are defined as: 
very common (≥ 1/10), common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare 

(≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from available 

data). 

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 

 

The most commonly reported adverse reactions of docetaxel alone are: neutropenia (which was 

reversible and not cumulative; the median day to nadir was 7 days and the median duration of severe 

neutropenia (< 500 cells/mm3) was 7 days), anaemia, alopecia, nausea, vomiting, stomatitis, diarrhoea 

and asthenia. The severity of adverse events of docetaxel may be increased when docetaxel is given in 

combination with other chemotherapeutic agents. 



58 

For combination with trastuzumab, adverse events (all grades) reported in ≥ 10% are displayed. There 

was an increased incidence of SAEs (40% vs. 31%) and Grade 4 AEs (34% vs. 23%) in the 

trastuzumab combination arm compared to docetaxel monotherapy. 

 

For combination with capecitabine, the most frequent treatment-related undesirable effects (≥ 5%) 

reported in a phase III study in breast cancer patients failing anthracycline treatment are presented (see 

capecitabine summary of product characteristics). 

 

For combination with ADT and with prednisone or prednisolone (STAMPEDE study), adverse events 

occurring occurring over the 6 cycles of treatment with docetaxel and having at least 2% higher 

incidence in the docetaxel treatment arm by comparison to the control arm, are presented, using the 

CTCAE grading scale. 

 

The following adverse reactions are frequently observed with docetaxel:  

 

Immune system disorders 

 

Hypersensitivity reactions have generally occurred within a few minutes following the start of the 

infusion of docetaxel and were usually mild to moderate. The most frequently reported symptoms 

were flushing, rash with or without pruritus, chest tightness, back pain, dyspnoea and fever or chills. 

Severe reactions were characterised by hypotension and/or bronchospasm or generalized 

rash/erythema (see section 4.4). 

 

Nervous system disorders 

 

The development of severe peripheral neurotoxicity requires a reduction of dose (see sections 4.2 and 

4.4). Mild to moderate neuro-sensory signs are characterised by paraesthesia, dysesthesia or pain 

including burning. Neuro-motor events are mainly characterised by weakness. 

 

Skin and subcutaneous tissue disorders 

 

Reversible cutaneous reactions have been observed and were generally considered as mild to 

moderate. Reactions were characterised by a rash including localised eruptions mainly on the feet and 

hands (including severe hand and foot syndrome), but also on the arms, face or thorax, and frequently 

associated with pruritus. Eruptions generally occurred within one week after the docetaxel infusion. 

Less frequently, severe symptoms such as eruptions followed by desquamation which rarely lead to 

interruption or discontinuation of docetaxel treatment were reported (see sections 4.2 and 4.4). Severe 

nail disorders are characterised by hypo- or hyperpigmentation and sometimes pain and onycholysis. 

 

General disorders and administration site conditions 

 

Infusion site reactions were generally mild and consisted of hyper pigmentation, inflammation, 

redness or dryness of the skin, phlebitis or extravasation and swelling of the vein.  

Fluid retention includes events such as peripheral oedema and less frequently pleural effusion, 

pericardial effusion, ascites and weight gain. The peripheral oedema usually starts at the lower 

extremities and may become generalised with a weight gain of 3 kg or more. Fluid retention is 

cumulative in incidence and severity (see section 4.4). 

 

Tabulated list of adverse reactions in breast cancer for DOCETAXEL KABI 100 mg/m² single agent 

 

MedDRA system 

organ classes 

Very common 

adverse reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infections 

(G3/4: 5.7%; including 

sepsis and pneumonia, 

fatal in 1.7%) 

Infection associated 

with G4 neutropenia 

(G3/4: 4.6%) 

  



59 

MedDRA system 

organ classes 

Very common 

adverse reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Blood and lymphatic 

system disorders 

Neutropenia 

(G4: 76.4%); 

Anaemia 

(G3/4: 8.9%); 

Febrile neutropenia 

Thrombocytopenia 

(G4: 0.2%) 

  

Immune system 

disorders 

Hypersensitivity 

(G3/4: 5.3%) 

    

Metabolism and 

nutrition disorders 

Anorexia     

Nervous system 

disorders 

Peripheral sensory 

neuropathy 

(G3: 4.1%); 

Peripheral motor 

neuropathy 

(G3/4: 4%); 

Dysgeusia 

(severe: 0.07%) 

    

Cardiac disorders   Arrhythmia 

(G3/4: 0.7%) 

Cardiac failure 

Vascular disorders   Hypotension; 

Hypertension; 

Haemorrhage 

  

Respiratory, thoracic 

and mediastinal 

disorders 

Dyspnoea 

(severe: 2.7%) 

    

Gastrointestinal 

disorders 

Stomatitis 

(G3/4: 5.3%); 

Diarrhoea (G3/4: 4%); 

Nausea (G3/4: 4%); 

Vomiting (G3/4: 3%) 

Constipation 

(severe: 0.2%); 

Abdominal pain 

(severe: 1%); 

Gastrointestinal 

haemorrhage 

(severe: 0.3%) 

Oesophagitis 

(severe: 0.4%) 

Skin and subcutaneous 

tissue disorders 

Alopecia; 

Skin reaction 

(G3/4: 5.9%); 

Nail disorders 

(severe: 2.6%) 

    

Musculoskeletal and 

connective tissue 

disorders 

Myalgia 

(severe: 1.4%) 

Arthralgia   

General disorders and 

administration site 

conditions 

Fluid retention 

(severe: 6.5%); 

Asthenia 

(severe: 11.2%); 

Pain 

Infusion site reaction;  

Non-cardiac chest pain 

(severe: 0.4%) 

  

Investigations   G3/4 Blood bilirubin 

increased (< 5%); 

G3/4 Blood alkaline 

  



60 

MedDRA system 

organ classes 

Very common 

adverse reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

phosphatase increased 

(< 4%);G3/4 AST 

increased (< 3%); 

G3/4 ALT increased 

(< 2%) 

 

Description of selected adverse reactions in breast cancer for DOCETAXEL KABI 100 mg/m² single 

agent 

 

Blood and lymphatic system disorders 

Rare: bleeding episodes associated with grade 3/4 thrombocytopenia.  

 

Nervous system disorders 

Reversibility data are available among 35.3% of patients who developed neurotoxicity following 

docetaxel treatment at 100 mg/m² as single agent. The events were spontaneously reversible within 

3 months. 

 

Skin and subcutaneous tissue disorders 

Very rare: one case of alopecia non-reversible at the end of the study. 73% of the cutaneous reactions 

were reversible within 21 days. 

 

General disorders and administration site conditions 

The median cumulative dose to treatment discontinuation was more than 1,000 mg/m2 and the median 

time to fluid retention reversibility was 16.4 weeks (range 0 to 42 weeks). The onset of moderate and 

severe retention is delayed (median cumulative dose: 818.9 mg/m2) in patients with premedication 

compared with patients without premedication (median cumulative dose: 489.7 mg/m2); however, it 

has been reported in some patients during the early courses of therapy. 

 

Tabulated list of adverse reactions in non-small cell lung cancer for DOCETAXEL KABI 75 mg/m² 

single agent 

 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Infections and infestations Infections (G3/4: 5%)   

Blood and lymphatic system 

disorders 

Neutropenia (G4: 54.2%); 

Anaemia (G3/4: 10.8%); 

Thrombocytopenia (G4: 1.7%) 

Febrile neutropenia 

Immune system disorders   Hypersensitivity (no severe) 

Metabolism and nutrition 

disorders 

Anorexia   

Nervous system disorders Peripheral sensory neuropathy 

(G3/4: 0.8%) 

Peripheral motor neuropathy 

(G3/4: 2.5%) 

Cardiac disorders   Arrhythmia (no severe) 

Vascular disorders   Hypotension 

Gastrointestinal disorders Nausea (G3/4: 3.3%); 

Stomatitis (G3/4: 1.7%); 

Vomiting (G3/4: 0.8%); 

Diarrhoea (G3/4: 1.7%) 

Constipation 



61 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Skin and subcutaneous tissue 

disorders 

Alopecia; 

Skin reaction (G3/4: 0.8%) 

Nail disorders (severe: 0.8%) 

Musculoskeletal and 

connective tissue disorders 

  Myalgia 

General disorders and 

administration site conditions 

Asthenia (severe: 12.4%); 

Fluid retention 

(severe: 0.8%);Pain 

  

Investigations   G3/4 Blood bilirubin 

increased (< 2%) 

 

Tabulated list of adverse reactions in breast cancer for DOCETAXEL KABI 75 mg/m² in combination 

with doxorubicin 

 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 7.8%)     

Blood and lymphatic 

system disorders 

Neutropenia 

(G4: 91.7%); 

Anaemia (G3/4: 9.4%); 

Febrile neutropenia; 

Thrombocytopenia 

(G4: 0.8%) 

    

Immune system 

disorders 

  Hypersensitivity 

(G3/4: 1.2%) 

  

Metabolism and 

nutrition disorders 

  Anorexia   

Nervous system 

disorders 

Peripheral sensory 

neuropathy (G3: 0.4%) 

Peripheral motor 

neuropathy 

(G3/4: 0.4%) 

  

Cardiac disorders   Cardiac failure; 

Arrhythmia (no 

severe) 

  

Vascular disorders     Hypotension 

Gastrointestinal 

disorders 

Nausea (G3/4: 5%); 

Stomatitis 

(G3/4: 7.8%); 

Diarrhoea 

(G3/4: 6.2%); 

Vomiting (G3/4: 5%); 

Constipation 

    

Skin and subcutaneous 

tissue disorders 

Alopecia; 

Nail disorders 

(severe: 0.4%); 

Skin reaction (no 

severe) 

    



62 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Musculoskeletal and 

connective tissue 

disorders 

  Myalgia   

General disorders and 

administration site 

conditions 

Asthenia 

(severe: 8.1%); 

Fluid retention 

(severe: 1.2%); 

Pain 

Infusion site reaction   

Investigations   G3/4 Blood bilirubin 

increased (< 2.5%); 

G3/4 Blood alkaline 

phosphatase increased 

(< 2.5%) 

G3/4 AST increased 

(< 1%); 

G3/4 ALT increased 

(< 1%) 

 

Tabulated list of adverse reactions in non-small cell lung cancer for DOCETAXEL KABI 75 mg/m² in 

combination with cisplatin 

 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 5.7%)     

Blood and 

lymphatic system 

disorders 

Neutropenia (G4: 51.5%); 

Anaemia (G3/4: 6.9%); 

Thrombocytopenia 

(G4: 0.5%) 

Febrile neutropenia   

Immune system 

disorders 

Hypersensitivity 

(G3/4: 2.5%) 

    

Metabolism and 

nutrition disorders 

Anorexia     

Nervous system 

disorders 

Peripheral sensory 

neuropathy (G3: 3.7%); 

Peripheral motor 

neuropathy (G3/4: 2%) 

    

Cardiac disorders   Arrhythmia 

(G3/4: 0.7%) 

Cardiac failure 

Vascular disorders   Hypotension 

(G3/4: 0.7%) 

  

Gastrointestinal 

disorders 

Nausea (G3/4: 9.6%); 

Vomiting (G3/4: 7.6%); 

Diarrhoea (G3/4: 6.4%); 

Stomatitis (G3/4: 2%) 

Constipation   

Skin and 

subcutaneous 

tissue disorders 

Alopecia; 

Nail disorders 

(severe: 0.7%); 

Skin reaction (G3/4: 0.2%) 

    

Musculoskeletal 

and connective 

Myalgia (severe: 0.5%)     



63 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

tissue disorders 

General disorders 

and administration 

site conditions 

Asthenia (severe: 9.9%); 

Fluid retention 

(severe: 0.7%); 

Fever (G3/4: 1.2%) 

Infusion site reaction; 

Pain 

  

Investigations   G3/4 Blood bilirubin 

increased (2.1%); G3/4 

ALT increased (1.3%) 

G3/4 AST increased 

(0.5%); G3/4 Blood 

alkaline phosphatase 

increased (0.3%) 

 

Tabulated list of adverse reactions in breast cancer for DOCETAXEL KABI 100 mg/m² in 

combination with trastuzumab 

 

MedDRA system 

organ classes 

Very common adverse reactions Common adverse reactions 

 

Blood and lymphatic 

system disorders 

Neutropenia (G3/4: 32%); 

Febrile neutropenia (includes 

neutropenia associated with fever and 

antibiotic use) or neutropenic sepsis  

  

Metabolism and 

nutrition disorders 

Anorexia   

Psychiatric disorders Insomnia   

Nervous system 

disorders 

Paraesthesia; Headache; Dysgeusia; 

Hypoaesthesia 

  

Eye disorders Lacrimation increased; Conjunctivitis   

Cardiac disorders   Cardiac failure 

Vascular disorders Lymphoedema   

Respiratory, thoracic 

and mediastinal 

disorders 

Epistaxis; Pharyngolaryngeal pain; 

Nasopharyngitis; Dyspnoea; 

Cough; Rhinorrhoea 

  

Gastrointestinal 

disorders 

Nausea; Diarrhoea; Vomiting; 

Constipation; Stomatitis; Dyspepsia; 

Abdominal pain 

  

Skin and 

subcutaneous tissue 

disorders 

Alopecia; Erythema; Rash; Nail 

disorders 

  

Musculoskeletal and 

connective tissue 

disorders 

Myalgia; Arthralgia; Pain in 

extremity; Bone pain; Back pain 

  

General disorders 

and administration 

site conditions 

Asthenia; Oedema peripheral; 

Pyrexia; Fatigue; Mucosal 

inflammation; Pain; Influenza like 

illness; Chest pain; Chills 

Lethargy 

Investigations Weight increased   

 



64 

Description of selected adverse reactions in breast cancer for DOCETAXEL KABI 100 mg/m² in 

combination with trastuzumab 

 

Cardiac disorders 

Symptomatic cardiac failure was reported in 2.2% of the patients who received docetaxel plus 

trastuzumab compared to 0% of patients given docetaxel alone. In the docetaxel plus trastuzumab arm, 

64% had received a prior anthracycline as adjuvant therapy compared with 55% in the docetaxel arm 

alone. 

 

Blood and lymphatic system disorders 

Very common: Haematological toxicity was increased in patients receiving trastuzumab and 

docetaxel, compared with docetaxel alone (32% grade 3/4 neutropenia versus 22%, using NCI-CTC 

criteria). Note that this is likely to be an underestimate since docetaxel alone at a dose of 100 mg/m2 is 

known to result in neutropenia in 97% of patients, 76% grade 4, based on nadir blood counts. The 

incidence of febrile neutropenia/neutropenic sepsis was also increased in patients treated with 

Herceptin plus docetaxel (23% versus 17% for patients treated with docetaxel alone). 

 

Tabulated list of adverse reactions in breast cancer for DOCETAXEL KABI 75 mg/m² in combination 

with capecitabine 

 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Infections and infestations   Oral candidiasis (G3/4: < 1%) 

Blood and lymphatic system 

disorders 

Neutropenia (G3/4: 63%); 

Anaemia (G3/4: 10%) 

Thrombocytopenia (G3/4: 3%) 

Metabolism and nutrition 

disorders 

Anorexia (G3/4: 1%); 

Decreased appetite 

Dehydration (G3/4: 2%) 

Nervous system disorders Dysgeusia (G3/4: < 1%); 

Paraesthesia (G3/4: < 1%) 

 

Dizziness; 

Headache (G3/4: < 1%); 

Neuropathy peripheral 

Eye disorders Lacrimation increased   

Respiratory, thoracic and 

mediastinal disorders 

Pharyngolaryngeal pain 

(G3/4: 2%) 

Dyspnoea (G3/4: 1%); 

Cough (G3/4: < 1%); 

Epistaxis (G3/4: < 1%) 

Gastrointestinal disorders Stomatitis (G3/4: 18%); 

Diarrhoea (G3/4: 14%); 

Nausea (G3/4: 6%); 

Vomiting (G3/4: 4%); 

Constipation (G3/4: 1%); 

Abdominal pain (G3/4: 2%); 

Dyspepsia 

Abdominal pain upper; 

Dry mouth 

Skin and subcutaneous tissue 

disorders 

Hand-foot syndrome 

(G3/4: 24%); 

Alopecia (G3/4: 6%); 

Nail disorders (G3/4: 2%) 

Dermatitis; 

Rash erythematous 

(G3/4: < 1%); 

Nail discolouration; 

Onycholysis (G3/4: 1%) 

Musculoskeletal and 

connective tissue disorders 

Myalgia (G3/4: 2%); 

Arthralgia (G3/4: 1%) 

Pain in extremity (G3/4: < 1%); 

Back pain (G3/4: 1%) 

General disorders and 

administration site conditions 

Asthenia (G3/4: 3%); 

Pyrexia (G3/4: 1%); 

Fatigue/weakness (G3/4: 5%); 

Lethargy; 

Pain 



65 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Oedema peripheral (G3/4: 1%) 

Investigations   Weight decreased; 

G3/4 Blood bilirubin increased 

(9%) 

 

Tabulated list of adverse reactions in metastatic castration-resistant prostate cancer for DOCETAXEL 

KABI 75 mg/m² in combination with prednisone or prednisolone 

 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Infections and infestations Infection (G3/4: 3.3%)   

Blood and lymphatic system 

disorders 

Neutropenia (G3/4: 32%); 

Anaemia (G3/4: 4.9%) 

Thrombocytopenia 

(G3/4: 0.6%); 

Febrile neutropenia 

Immune system disorders   Hypersensitivity (G3/4: 0.6%) 

Metabolism and nutrition 

disorders 

Anorexia (G3/4: 0.6%)   

Nervous system disorders Peripheral sensory neuropathy 

(G3/4: 1.2%); 

Dysgeusia (G3/4: 0%) 

Peripheral motor neuropathy 

(G3/4: 0%) 

Eye disorders   Lacrimation increased 

(G3/4: 0.6%) 

Cardiac disorders   Cardiac left ventricular 

function decrease (G3/4: 0.3%) 

Respiratory, thoracic and 

mediastinal disorders 

  Epistaxis (G3/4: 0%); 

Dyspnoea (G3/4: 0.6%); 

Cough (G3/4: 0%) 

Gastrointestinal disorders Nausea (G3/4: 2.4%); 

Diarrhoea (G3/4: 1.2%); 

Stomatitis/Pharyngitis 

(G3/4: 0.9%); 

Vomiting (G3/4: 1.2%) 

  

Skin and subcutaneous tissue 

disorders 

Alopecia; 

Nail disorders (no severe) 

Exfoliative rash (G3/4: 0.3%) 

Musculoskeletal and 

connective bone disorders 

  Arthralgia (G3/4: 0.3%); 

Myalgia (G3/4: 0.3%) 

General disorders and 

administration site conditions 

Fatigue (G3/4: 3.9%); 

Fluid retention (severe: 0.6%) 

  

 



66 

Tabulated list of adverse reactions in high-risk locally advanced or metastatic hormone-sensitive 

prostate cancer for DOCETAXEL KABI 75 mg/m² in combination with prednisone or prednisolone 

and ADT (STAMPEDE study)  

 

MedDRA system organ 

classes 

 

Very common adverse 

reactions 

Common adverse reactions 

Blood and lymphatic system 

disorders 

Neutropenia (G3-4: 12 %) 

Anaemia  

Febrile neutropenia (G3-4: 15%) 

 

Immune system disorders   Hypersensitivity (G3-4: 1%) 

Endocrine disorders  Diabetes (G3-4: 1%) 

Metabolism and nutrition 

disorders 

 Anorexia  

Psychiatric disorders Insomnia (G3: 1%)  

Nervous system disorders Peripheral sensory neuropathy 

(≥G3: 2%)a 

Headache 

 

Dizziness 

Eye disorders  Blurred vision 

Cardiac disorders  Hypotension (G3: 0%) 

 

Respiratory, thoracic and 

mediastinal disorders  

Dyspnea (G3: 1%) 

Coughing (G3: 0%) 

Upper respiratory tract infection 

(G3: 1%)  

Pharyngitis (G3: 0%) 

 

 

Gastrointestinal disorders  Diarrhea (G3: 3%) 

Stomatitis (G3: 0%) 

Constipation (G3: 0%) 

Nausea (G3: 1%) 

Dyspepsia 

Abdominal pain (G3: 0%) 

Flatulence 

Vomiting (G3: 1%) 

 

Skin and subcutaneous tissue 

disorders 

Alopecia (G3: 3%)a 

Nail changes (G3: 1%) 

Rash 

Musculoskeletal and 

connective tissue disorders 

Myalgia   

General disorders and 

administration site conditions 

Lethargy (G3-4: 2%) 

Flu-like symptoms (G3: 0%) 

Asthenia (G3: 0%) 

Fluid retention 

Fever (G3: 1%) 

Oral candidiasis  

Hypocalcaemia (G3: 0%) 

Hypophosphataemia (G3-4: 1%) 

Hypokalaemia (G3: 0%) 
a From the GETUG AFU15 study 
 

Tabulated list of adverse reactions in breast cancer for adjuvant therapy with DOCETAXEL KABI 

75 mg/m² in combination with doxorubicin and cyclophosphamide in patients with node-positive 

(TAX 316) and node-negative (GEICAM 9805) breast cancer - pooled data 

 



67 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 2.4%); 

Neutropenic infection 

(G3/4: 2.6%) 

    

Blood and 

lymphatic system 

disorders 

Anaemia (G3/4: 3%); 

Neutropenia 

(G3/4: 59.2%); 

Thrombocytopenia 

(G3/4: 1.6%); 

Febrile neutropenia 

(G3/4: NA) 

    

Immune system 

disorders 

  Hypersensitivity 

(G3/4: 0.6 %) 

  

Metabolism and 

nutrition disorders 

Anorexia (G3/4: 1.5%)     

Nervous system 

disorders 

Dysgeusia (G3/4: 0.6%); 

Peripheral sensory 

neuropathy 

(G3/4: < 0.1%) 

Peripheral motor 

neuropathy 

(G3/4: 0%) 

Syncope (G3/4: 0%); 

Neurotoxicity 

(G3/4: 0%); 

Somnolence (G3/4: 0%) 

Eye disorders  Conjunctivitis 

(G3/4: < 0.1%) 

Lacrimation 

increased 

(G3/4:  < 0.1%) 

  

Cardiac disorders   Arrhythmia 

(G3/4: 0.2%) 

  

Vascular disorders Hot flush (G3/4: 0.5%) Hypotension 

(G3/4: 0%); 

Phlebitis 

(G3/4: 0%) 

Lymphoedema 

(G3/4: 0%) 

Respiratory, 

thoracic and 

mediastinal 

disorders 

  Cough (G3/4: 0%)   

Gastrointestinal 

disorders 

Nausea (G3/4: 5.0%); 

Stomatitis (G3/4: 6.0%); 

Vomiting (G3/4: 4.2%); 

Diarrhoea (G3/4: 3.4%); 

Constipation 

(G3/4: 0.5%) 

Abdominal pain 

(G3/4: 0.4%) 

 

Skin and 

subcutaneous tissue 

disorders 

Alopecia 

(persisting: <3%); 

Skin disorder  

(G3/4: 0.6%); 

Nail disorders 

(G3/4: 0.4%) 

    

Musculoskeletal 

and connective 

tissue disorders 

Myalgia (G3/4: 0.7%); 

Arthralgia (G3/4: 0.2%) 

    

Reproductive Amenorrhoea      



68 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

system and breast 

disorders 

(G3/4: NA) 

General disorders 

and administration 

site conditions 

Asthenia  

(G3/4: 10.0%); 

Pyrexia (G3/4: NA); 

Oedema peripheral 

(G3/4: 0.2%) 

    

Investigations   Weight increased 

(G3/4: 0%); 

Weight decreased 

(G3/4: 0.2%) 

  

 

Description of selected adverse reactions for adjuvant therapy with DOCETAXEL KABI 75 mg/m² in 

combination with doxorubicin and cyclophosphamide in patients with node-positive (TAX 

316) and node-negative (GEICAM 9805) breast cancer 

 

Nervous system disorders 

In study TAX316 peripheral sensory neuropathy started during the treatment period and persisted into 

the follow-up period in 84 patients (11.3%) in TAC arm and 15 patients (2 %) in FAC arm. At the end 

of the follow-up period (median follow-up time of 8 years), peripheral sensory neuropathy was 

observed to be ongoing in 10 patients (1.3%) in TAC arm, and in 2 patients (0.3%) in FAC arm. 

In GEICAM 9805 study peripheral sensory neuropathy that started during the treatment period 

persisted into the follow-up period in 10 patients (1.9%) in TAC arm and 4 patients (0.8 %) in FAC 

arm. At the end of the follow-up period (median follow-up time of 10 years and 5 months), peripheral 

sensory neuropathy was observed to be ongoing in 3 patients (0.6%) in TAC arm, and in 1 patient 

(0.2%) in FAC arm. 

 

Cardiac disorders 

In study TAX316, 26 patients (3.5%) in the TAC arm and 17 patients (2.3%) in the FAC arm 

experienced congestive heart failure. All except one patient in each arm were diagnosed with CHF 

more than 30 days after the treatment period. Two patients in the TAC arm and 4 patients in the FAC 

arm died because of cardiac failure. 

In GEICAM 9805 study, 3 patients (0.6 %) in TAC arm and 3 patients (0.6 %) in FAC arm developed 

congestive heart failure during the follow-up period.  At the end of the follow-up period (actual 

median follow-up time of 10 years and 5 months), no patients had CHF in TAC arm and 1 patient in 

TAC arm died because of dilated cardiomyopathy, and CHF was observed to be ongoing in 1 patient 

(0.2%) in FAC arm. 

 

Skin and subcutaneous tissue disorders 

In study TAX316 alopecia persisting into the follow-up period after the end of chemotherapy was 

reported in 687 of 744 TAC patients (92.3%) and 645 of 736 FAC patients (87.6%). 

At the end of the follow-up period (actual median follow-up time of 8 years), alopecia was observed to 

be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%). 

In GEICAM 9805 study alopecia that started during the treatment period and persisted into the follow-

up period and was observed to be ongoing in 49 patients (9.2 %) in TAC arm and 35 patients (6.7 %) 

in FAC arm. Alopecia related to study drug started or worsened during the follow-up period in 

42 patients (7.9 %) in TAC arm and 30 patients (5.8 %) in FAC arm. At the end of the follow-up 

period (median follow-up time of 10 years and 5 months), alopecia was observed to be ongoing in 3 

patients (0.6%) in TAC arm, and in 1 patient (0.2%) in FAC arm.   

Reproductive system and breast disorders 

 In TAX316 amenorrhoea that started during the treatment period and persisted into the follow-up 

period after the end of chemotherapy was reported in 202 of 744 TAC patients (27.2%) and 125 of 736 



69 

FAC patients (17.0%). Amenorrhea was observed to be ongoing at the end of the follow-up period 

(median follow-up time of 8 years) in 121 of 744 TAC patients (16.3%) and 86 FAC patients (11.7%). 

In GEICAM 9805 study amenorrhoea that started during the treatment period and persisted into the 

follow-up period was observed to be ongoing in 18 patients (3.4 %) in TAC arm and 5 patients (1.0 %) 

in FAC arm. At the end of the follow-up period (median follow-up time of 10 years and 5 months), 

amenorrhoea was observed to be ongoing in 7 patients (1.3%) in TAC arm, and in 4 patients (0.8%) in 

FAC arm. 

 

General disorders and administration site conditions 

In study TAX316 peripheral oedema that started during the treatment period and persisted into the 

follow-up period after the end of chemotherapy was observed in 119 of 744 TAC patients (16.0%) and 

23 of 736 FAC patients (3.1%). At the end of the follow-up period (actual median follow-up time of 8 

years), peripheral oedema was ongoing in19 TAC patients (2.6%) and 4 FAC patients (0.5%).  

In study TAX316 lymphoedema that started during the treatment period and persisted into the follow-

up period after the end of chemotherapy was reported in 11 of 744 TAC patients (1.5%) and 1 of 736 

FAC patients (0.1%). At the end of the follow-up period (actual median follow-up time of 8 years), 

lymphoedema was observed to be ongoing in 6 TAC patients (0.8%) and 1 FAC patient (0.1%). 

In study TAX316 asthenia that started during the treatment period and persisted into the follow-up 

period after the end of chemotherapy was reported in 236 of 744 TAC patients (31.7%) and 180 of 736 

FAC patients (24.5%). At the end of the follow-up period (actual median follow-up time of 8 years), 

asthenia was observed to be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%). 

 

In study GEICAM 9805 peripheral oedema that started during the treatment period persisted into the 

follow-up period in 4 patients (0.8%) in TAC arm and in 2 patients (0.4%) in FAC arm. At the end of 

the follow-up period (median follow-up time of 10 years and 5 months), no patients (0%) in TAC arm 

had peripheral oedema and it was observed to be ongoing in 1 patient (0.2%) in FAC arm. 

Lymphoedema that started during the treatment period persisted into the follow-up period in 5 patients 

(0.9%) in TAC arm and 2 patients (0.4 %) in FAC arm. At the end of the follow-up period, 

lymphoedema was observed to be ongoing in 4 patients (0.8%) in TAC arm, and in 1 patient (0.2%) in 

FAC arm.  

 

Asthenia that started during the treatment period and persisted into the follow-up period was observed 

to be ongoing in 12 patients (2.3 %) in TAC arm and 4 patients (0.8 %) in FAC arm. At the end of the 

follow-up period, asthenia was observed to be ongoing in 2 patients (0.4%) in TAC arm, and in 2 

patients (0.4%) in FAC arm. 

 

Acute leukaemia / Myelodysplastic syndrome 

After 10 years of follow up in study TAX316, acute leukaemia was reported in 3of 744 TAC patients 

(0.4%) and in 1 of 736 FAC patients (0.1%). One TAC patient (0.1%) and 1 FAC patient (0.1%) died 
due to AML during the follow-up period (median follow-up time of 8 years).  Myelodysplastic 

syndrome was reported in 2 of 744 TAC patients (0.3%) and in 1 of 736 FAC patients (0.1%). 

After 10 years of follow-up in GEICAM 9805 study, acute leukaemia occurred in 1 of 532 (0.2%) 

patients in TAC arm. No cases were reported in patients in FAC arm. No patient was diagnosed with 

myelodysplastic syndrome in either treatment groups. 

 

Neutropenic complications 

Table below shows that the incidence of Grade 4 neutropenia, febrile neutropenia and neutropenic 

infection was decreased in patients who received primary G-CSF prophylaxis after it was made 

mandatory in the TAC arm – GEICAM study. 

 

Neutropenic complications in patients receiving TAC with or without primary G-CSF prophylaxis 

(GEICAM 9805) 

 

 

 

 

 



70 

 Without primary 

G-CSF prophylaxis 

(n = 111) 

n (%) 

With primary 

G-CSF prophylaxis 

(n = 421) 

n (%) 

Neutropenia (Grade 4) 104 (93.7) 135 (32.1) 

Febrile neutropenia 28 (25.2) 23 (5.5) 

Neutropenic infection 14 (12.6) 21 (5.0) 

Neutropenic infection 

(Grade 3-4) 

2 (1.8) 5 (1.2) 

 

Tabulated list of adverse reactions in gastric adenocarcinoma center for DOCETAXEL KABI 

75 mg/m² in combination with cisplatin and 5-fluorouracil 

 

MedDRA system organ 

classes 

Very common adverse reactions Common adverse reactions 

Infections and 

infestations 

Neutropenic infection; 

Infection (G3/4: 11.7%) 

  

Blood and lymphatic 

system disorders 

Anaemia (G3/4: 20.9%); 

Neutropenia (G3/4: 83.2%); 

Thrombocytopenia (G3/4: 8.8%); 

Febrile neutropenia  

  

Immune system 

disorders 

Hypersensitivity (G3/4: 1.7%)   

Metabolism and nutrition 

disorders 

Anorexia (G3/4: 11.7%)   

Nervous system 

disorders 

Peripheral sensory neuropathy 

(G3/4: 8.7%) 

Dizziness (G3/4: 2.3%); 

Peripheral motor neuropathy 

(G3/4: 1.3%) 

Eye disorders   Lacrimation increased (G3/4: 0%) 

Ear and labyrinth 

disorders 

  Hearing impaired (G3/4: 0%) 

Cardiac disorders   Arrhythmia (G3/4: 1.0%) 

Gastrointestinal disorders Diarrhoea (G3/4: 19.7%); 

Nausea (G3/4: 16%); 

Stomatitis (G3/4: 23.7%); 

Vomiting (G3/4: 14.3%) 

Constipation (G3/4: 1.0%); 

Gastrointestinal pain (G3/4: 1.0%); 

Oesophagitis/dysphagia/ 

odynophagia (G3/4: 0.7%) 

Skin and subcutaneous 

tissue disorders 

Alopecia (G3/4: 4.0%) Rash pruritus (G3/4: 0.7%); 

Nail disorders (G3/4: 0.7%); 

Skin exfoliation (G3/4: 0%) 

General disorders and 

administration site 

conditions 

Lethargy (G3/4: 19.0%); 

Fever (G3/4: 2.3%); 

Fluid retention (severe/life-

threatening: 1%) 

  

 

Description of selected adverse reactions in gastric adenocarcinoma cancer for DOCETAXEL KABI 

75 mg/m2 in combination with cisplatin and 5-fluorouracil 

 

Blood and lymphatic system disorders 

Febrile neutropenia and neutropenic infection occurred in 17.2% and 13.5% of patients respectively, 

regardless of G-CSF use. G-CSF was used for secondary prophylaxis in 19.3% of patients (10.7% of 



71 

the cycles). Febrile neutropenia and neutropenic infection occurred respectively in 12.1% and 3.4% of 

patients when patients received prophylactic G-CSF, in 15.6% and 12.9% of patients without 

prophylactic G-CSF (see section 4.2). 

 

Tabulated list of adverse reactions in head and neck cancer for DOCETAXEL KABI 75 mg/m² in 

combination with cisplatin and 5-fluorouracil  

 

• Induction chemotherapy followed by radiotherapy (TAX 323)  
 

MedDRA system 

organ classes 

Very common adverse 

reactions 

 

Common adverse 

reactions 

 

Uncommon 

adverse reactions 

Infections and 

infestations 

Infection (G3/4: 6.3%); 

Neutropenic infection 

    

Neoplasms benign, 

malignant and 

unspecified (incl cysts 

and polyps) 

  Cancer pain (G3/4: 0.6%)   

Blood and lymphatic 

system disorders 

Neutropenia 

(G3/4: 76.3%); 

Anaemia (G3/4: 9.2%); 

Thrombocytopenia 

(G3/4: 5.2%) 

Febrile neutropenia   

Immune system 

disorders 

  Hypersensitivity (no 

severe) 

  

Metabolism and 

nutrition disorders 

Anorexia (G3/4: 0.6%)     

Nervous system 

disorders 

Dysgeusia/Parosmia; 

Peripheral sensory 

neuropathy (G3/4: 0.6%) 

Dizziness   

Eye disorders   Lacrimation increased; 

Conjunctivitis  

  

Ear and labyrinth 

disorders 

  Hearing impaired   

Cardiac disorders   Myocardial ischemia 

(G3/4: 1.7%) 

Arrhythmia 

(G3/4: 0.6%) 

Vascular disorders   Venous disorder 

(G3/4: 0.6%) 

  

Gastrointestinal 

disorders 

Nausea (G3/4: 0.6%); 

Stomatitis (G3/4: 4.0%); 

Diarrhoea (G3/4: 2.9%); 

Vomiting (G3/4: 0.6%) 

Constipation; 

Esophagitis/dysphagia/ 

odynophagia (G3/4: 0.6%); 

Abdominal pain; 

Dyspepsia; 

Gastrointestinal 

haemorrhage (G3/4: 0.6%)  

  

Skin and subcutaneous 

tissue disorders 

Alopecia (G3/4: 10.9%) Rash pruritic; 

Dry skin; 

Skin exfoliative 

(G3/4: 0.6%) 

  



72 

MedDRA system 

organ classes 

Very common adverse 

reactions 

 

Common adverse 

reactions 

 

Uncommon 

adverse reactions 

Musculoskeletal and 

connective tissue 

disorders 

  Myalgia (G3/4: 0.6%)   

General disorders and 

administration site 

conditions 

Lethargy (G3/4: 3.4%); 

Pyrexia (G3/4: 0.6%); 

Fluid retention; 

Oedema 

    

Investigations   Weight increased   

 

• Induction chemotherapy followed by chemoradiotherapy (TAX 324)  
 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 3.6%) 

  

Neutropenic 

infection 

  

Neoplasms benign, 

malignant and 

unspecified (incl 

cysts and polyps) 

  Cancer pain 

(G3/4: 1.2%) 

  

Blood and lymphatic 

system disorders 

Neutropenia 

(G3/4: 83.5%); 

Anaemia (G3/4: 12.4%); 

Thrombocytopenia 

(G3/4: 4.0%); 

Febrile neutropenia 

    

Immune system 

disorders 

    Hypersensitivity 

Metabolism and 

nutrition disorders 

Anorexia (G3/4: 12.0%)     

Nervous system 

disorders 

Dysgeusia/Parosmia 

(G3/4: 0.4%); 

Peripheral sensory 

neuropathy (G3/4: 1.2%) 

Dizziness 

(G3/4: 2.0%); 

Peripheral motor 

neuropathy 

(G3/4: 0.4%) 

  

Eye disorders   Lacrimation 

increased 

Conjunctivitis 

Ear and labyrinth 

disorders 

Hearing impaired 

(G3/4: 1.2%) 

    

Cardiac disorders   Arrhythmia 

(G3/4: 2.0%) 

Ischemia myocardial 

Vascular disorders     Venous disorder 

Gastrointestinal 

disorders 

Nausea (G3/4: 13.9%); 

Stomatitis (G3/4: 20.7%); 

Vomiting (G3/4: 8.4%); 

Diarrhoea (G3/4: 6.8%); 

Dyspepsia 

(G3/4: 0.8%); 

Gastrointestinal pain 

(G3/4: 1.2%); 

  



73 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Esophagitis/dysphagia/ 

odynophagia 

(G3/4: 12.0%); 

Constipation (G3/4: 0.4%) 

Gastrointestinal 

haemorrhage 

(G3/4: 0.4%) 

Skin and 

subcutaneous tissue 

disorders 

Alopecia (G3/4: 4.0%); 

Rash pruritic 

Dry skin ; 

Desquamation 

  

Musculoskeletal, 

connective tissue 

bone disorders 

  Myalgia 

(G3/4: 0.4%) 

  

General disorders and 

administration site 

conditions 

Lethargy (G3/4: 4.0%); 

Pyrexia (G3/4: 3.6%); 

Fluid retention (G3/4: 1.2); 

Oedema (G3/4: 1.2%) 

    

Investigations Weight decreased   Weight increased 

 

Post-marketing experience 

 

Neoplasms benign, malignant and unspecified (incl cysts and polyps) 

Second primary malignancies (frequency not known), including non-Hodgkin lymphoma have been 

reported in association with docetaxel when used in combination with other anticancer treatments 

known to be associated with second primary malignancies. Acute myeloid leukemia and 

myelodysplastic syndrome have been reported (frequency uncommon) in pivotal clinical studies in 

breast cancer with TAC regimen. 

 

Blood and lymphatic system disorders 

Bone marrow suppression and other haematologic adverse reactions have been reported. Disseminated 

intravascular coagulation (DIC), often in association with sepsis or multi-organ failure, has been 

reported. 

 

Immune system disorders 

Some cases of anaphylactic shock, sometimes fatal, have been reported. 

Hypersensitivity reactions (frequency not known) have been reported with docetaxel in patients who 

previously experienced hypersensitivity reactions to paclitaxel. 

 

Nervous system disorders 

Rare cases of convulsion or transient loss of consciousness have been observed with docetaxel 

administration. These reactions sometimes appear during the infusion of the medicinal product. 

 

Eye disorders 

Very rare cases of transient visual disturbances (flashes, flashing lights, scotomata) typically occurring 

during infusion of the medicinal product and in association with hypersensitivity reactions have been 

reported. These were reversible upon discontinuation of the infusion. Cases of lacrimation with or 

without conjunctivitis, as cases of lacrimal duct obstruction resulting in excessive tearing have been 

rarely reported. Cases of cystoid macular oedema (CMO) have been reported in patients treated with 

docetaxel. 

 

Ear and labyrinth disorders 

Rare cases of ototoxicity, hearing impaired and/or hearing loss have been reported. 

 

Cardiac disorders 

Rare cases of myocardial infarction have been reported. 



74 

Ventricular arrhythmia including ventricular tachycardia (frequency not known), sometimes fatal, has 

been reported in patients treated with docetaxel in combination regimens including doxorubicin, 5-

fluorouracil and/ or cyclophosphamide. 

 

Vascular disorders 

Venous thromboembolic events have rarely been reported. 

 

Respiratory, thoracic and mediastinal disorders 

Acute respiratory distress syndrome and cases of interstitial pneumonia/ pneumonitis, interstitial lung 
disease, pulmonary fibrosis and respiratory failure sometimes fatal have rarely been reported. Rare 

cases of radiation pneumonitis have been reported in patients receiving concomitant radiotherapy. 

 

Gastrointestinal disorders 

Rare cases of enterocolitis, including colitis, ischemic colitis, and neutropenic enterocolitis, have been 

reported with a potential fatal outcome (frequency not known). 

Rare occurrences of dehydration have been reported as a consequence of gastrointestinal events 

including enterocolitis and gastrointestinal perforation.  

Rare cases of ileus and intestinal obstruction have been reported. 

 

Hepatobiliary disorders 

Very rare cases of hepatitis, sometimes fatal primarily in patients with pre-existing liver disorders, 

have been reported. 

 

 

Skin and subcutaneous tissue disorders 

Cases of cutaneous lupus erythematosus, bullous eruptions such as erythema multiforme and severe 

cutaneous adverse reactions such as Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis 

(TEN) and Acute Generalized Exanthematous Pustulosis (AGEP) have been reported with docetaxel.  

Scleroderma-like changes usually preceded by peripheral lymphoedema have been reported with 

docetaxel. Cases of permanent alopecia (frequency not known) have been reported. 

 

Renal and urinary disorders 

Renal insufficiency and renal failure have been reported. In about 20% of these cases there were no 

risk factors for acute renal failure such as concomitant nephrotoxic medicinal products and 

gastrointestinal disorders. 

 

General disorders and administration site conditions 

Radiation recall phenomena have rarely been reported. 

Injection site recall reaction (recurrence of skin reaction at a site of previous extravasation following 

administration of docetaxel at a different site) has been observed at the site of previous extravasation 

(frequency not known). 

Fluid retention has not been accompanied by acute episodes of oliguria or hypotension. Dehydration 

and pulmonary oedema have rarely been reported. 

 

Metabolism and nutrition disorders 

Cases of electrolyte imbalance have been reported. Cases of hyponatraemia have been reported, 

mostly associated with dehydration, vomiting and pneumonia. Hypokalaemia, hypomagnesaemia, and 

hypocalcaemia were observed, usually in association with gastrointestinal disorders and in particular 

with diarrhoea. 

 

Reporting of suspected adverse reactions 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

 



75 

4.9 Overdose 

 

There were a few reports of overdose. There is no known antidote for docetaxel overdose. In case of 

overdose, the patient should be kept in a specialised unit and vital functions closely monitored. In 

cases of overdose, exacerbation of adverse events may be expected. The primary anticipated 

complications of overdose would consist of bone marrow suppression, peripheral neurotoxicity and 

mucositis. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. 

Other appropriate symptomatic measures should be taken, as needed. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: antineoplastic agents, plant alkaloids and other natural products, taxanes, 

ATC Code: L01CD02  

 

Mechanism of action 

 

Docetaxel is an antineoplastic agent which acts by promoting the assembly of tubulin into stable 

microtubules and inhibits their disassembly which leads to a marked decrease of free tubulin. The 

binding of docetaxel to microtubules does not alter the number of protofilaments. 

 

Docetaxel has been shown in vitro to disrupt the microtubular network in cells which is essential for 

vital mitotic and interphase cellular functions. 

 

Pharmacodynamic effects 

 

Docetaxel was found to be cytotoxic in vitro against various murine and human tumour cell lines and 

against freshly excised human tumour cells in clonogenic assays. Docetaxel achieves high intracellular 

concentrations with a long cell residence time. In addition, docetaxel was found to be active on some 

but not all cell lines over expressing the p-glycoprotein which is encoded by the multidrug resistance 

gene. In vivo, docetaxel is schedule independent and has a broad spectrum of experimental anti-tumour 

activity against advanced murine and human grafted tumours. 

 

Clinical efficacy and safety 

 

Breast cancer 

 

DOCETAXEL KABI in combination with doxorubicin and cyclophosphamide: adjuvant therapy 

 

Patients with operable node-positive breast cancer (TAX 316) 

 

Data from a multi-centre open-label randomised study support the use of docetaxel for the adjuvant 
treatment of patients with operable node-positive breast cancer and KPS ≥ 80%, between 18 and 

70 years of age. After stratification according to the number of positive lymph nodes (1-3, 

4+), 1491 patients were randomised to receive either docetaxel 75 mg/m2 administered 1-hour after 
doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (TAC arm), or doxorubicin 50 mg/m2 

followed by fluorouracil 500 mg/m2 and cyclosphosphamide 500 mg/m2 (FAC arm). Both regimens 

were administered once every 3 weeks for 6 cycles. Docetaxel was administered as a 1-hour infusion, 

all other medicinal products were given as intravenous bolus on day one. G-CSF was administered as 

secondary prophylaxis to patients who experienced complicated neutropenia (febrile neutropenia, 

prolonged neutropenia, or infection). Patients on the TAC arm received antibiotic prophylaxis with 

ciprofloxacin 500 mg orally twice daily for 10 days starting on day 5 of each cycle, or equivalent. In 

both arms, after the last cycle of chemotherapy, patients with positive oestrogen and/or progesterone 

receptors received tamoxifen 20 mg daily for up to 5 years. Adjuvant radiation therapy was prescribed 

according to guidelines in place at participating institutions and was given to 69% of patients who 



76 

received TAC and 72% of patients who received FAC. Two interim analyses and one final analysis 

were performed. The first interim analysis was planned 3 years after the date when half of study 

enrolment was done. The second interim analysis was done after 400 DFS events had been recorded 

overall, which led to a median follow-up of 55 months. The final analysis was performed when all 

patients had reached their 10-year follow-up visit (unless they had a DFS event or were lost to follow 

up before). Disease-free survival (DFS) was the primary efficacy endpoint and Overall survival (OS) 

was the secondary efficacy endpoint. 

 

A final analysis was performed with an actual median follow up of 96 months. Significantly longer 

disease-free survival for the TAC arm compared to the FAC arm was demonstrated. Incidence of 

relapses at 10 years was reduced in patients receiving TAC compared to those who received FAC 

(39% versus 45%, respectively) i.e. an absolute risk reduction by 6% (p = 0.0043). Overall survival at 

10 years was also significantly increased with TAC compared to FAC (76% versus 69%, respectively) 

i.e. an absolute reduction of the risk of death by 7% (p = 0.002). As the benefit observed in patients 

with 4+ nodes was not statistically significant on DFS and OS, the positive benefit/risk ratio for TAC 

in patients with 4+ nodes was not fully demonstrated at the final analysis. 

 

Overall, the study results demonstrate a positive benefit risk ratio for TAC compared to FAC. 

 

TAC-treated patient subsets according to prospectively defined major prognostic factors were 

analysed:  

 

  Disease free survival Overall Survival 

Patient 

subset 

Number 

of patients 

Hazard 

ratio* 

95% CI p = Hazard 

ratio* 

95% CI p = 

No of 

positive 

nodes 

Overall 

1-3 

4+ 

 

 

 

745 

467 

278 

 

 

 

0.80 

0.72 

0.87 

 

 

 

0.68-0.93 

0.58-0.91 

0.70-1.09 

 

 

 

0.0043 

0.0047 

0.2290 

 

 

 

0.74 

0.62 

0.87 

 

 

 

0.61-0.90 

0.46-0.82 

0.67-1.12 

 

 

 

0.0020 

0.0008 

0.2746 

*a hazard ratio of less than 1 indicates that TAC is associated with a longer disease-free survival and 

overall survival compared to FAC  

 

Patients with operable node-negative breast cancer eligible to receive chemotherapy (GEICAM 9805) 

 

Data from a multi-centre open-label randomised trial support the use of DOCETAXEL KABI for the 

adjuvant treatment of patients with operable node-negative breast cancer eligible to receive 

chemotherapy. 1060 patients were randomised to receive either DOCETAXEL KABI 75 mg/m2 

administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (539 patients in 

TAC arm), or doxorubicin 50 mg/m2 followed by fluorouracil 500 mg/m2 and cyclosphosphamide 

500 mg/m2 (521 patients in FAC arm), as adjuvant treatment of operable node-negative breast cancer 

patients with high risk of relapse according to 1998 St. Gallen criteria (tumour size > 2 cm and/or 

negative ER and PR and/or high histological/nuclear grade (grade 2 to 3) and /or age < 35 years).). 

Both regimens were administered once every 3 weeks for 6 cycles. DOCETAXEL KABI was 

administered as a 1-hour infusion, all other medicinal product were given intraveinously on day 1 

every three weeks. Primary prophylactic G-CSF was made mandatory in TAC arm after 230 patients 

were randomised. The incidence of Grade 4 neutropenia, febrile neutropenia and neutropenic infection 

was decreased in patients who received primary G-CSF prophylaxis (see section 4.8). In both arms, 

after the last cycle of chemotherapy, patients with ER+ and/or PgR+ tumours received tamoxifen 

20 mg once a day for up to 5 years. Adjuvant radiation therapy was administered according to 

guidelines in place at participating institutions and was given to 57.3% of patients who received TAC 

and 51.2% of patients who received FAC. 

 



77 

One primary analysis and one updated analysis were performed. The primary analysis was done when 

all patients had a follow-up of greater than 5 years (median follow-up time of 77 months). The updated 

analysis was performed when all patients had reached their 10-year (median follow up time of 10 

years and 5 months) follow-up visit (unless they had a DFS event or were lost to follow-up 

previously). Disease-free survival (DFS) was the primary efficacy endpoint and Overall survival (OS) 

was the secondary efficacy endpoint. 

 

At the median follow-up was 77 months, significantly longer disease-free survival for the TAC arm 

compared to the FAC arm was demonstrated. TAC-treated patients had a 32% reduction in the risk of 

relapse compared to those treated with FAC (hazard ratio = 0.68, 95% CI (0.49-0.93), p = 0.01). At the 

median follow up time of 10 years and 5 months, TAC-treated patients had a 16,5% reduction in the 

risk of relapse compared to those treated with FAC (hazard ratio = 0.84, 95% CI (0.65-1.08), 

p=0.1646). DFS data were not statistically significant but were still associated with a positive trend in 

favour of TAC.   

 

At the median follow-up time of 77 months overall survival (OS) was longer in the TAC arm with 

TAC-treated patients having a 24% reduction in the risk of death compared to FAC (hazard ratio = 

0.76, 95% CI (0.46-1.26, p = 0.29). However, the distribution of OS was not significantly different 

between the 2 groups. 

At the median follow up time of 10 years and 5 months, TAC-treated patients had a 9% reduction in 

the risk of death compared to FAC-treated patients (hazard ratio = 0.91, 95% CI (0.63-1.32)).  

The survival rate was 93.7% in the TAC arm and 91.4 % in the FAC arm, at the 8-year follow-up time 

point, and 91.3 % in the TAC arm and 89 % in the FAC arm, at the 10-year follow-up time point. 

 

The positive benefit risk ratio for TAC compared to FAC remained unchanged.   

 

TAC-treated patient subsets according to prospectively defined major prognostic factors were analysed 

in the primary analysis (at the median follow-up time of 77 months) (see table below): 

 

Subset Analyses-Adjuvant Therapy in Patients with Node-negative Breast Cancer Study 

(Intent-to-Treat Analysis) 

 

Patient subset Number of patients 

in TAC group 

Disease Free Survival 

Hazard ratio* 95% CI 

Overall 539 0.68 0.49-0.93 

Age category 1 

<50 years  

≥50 years 

 

260 

279  

 

0.67 

0.67  

 

0.43-1.05 

0.43-1.05 

Age category 2 

<35 years 

≥35 years 

 

42 

497 

 

0.31 

0.73 

 

0.11-0.89 

0.52-1.01 

Hormonal receptor 

status 

Negative  

Positive 

 

 

195 

344 

 

 

0.7 

0.62 

 

 

0.45-1.1 

0.4-0.97 

Tumour size 

≤2 cm  

>2 cm 

 

285 

254 

 

0.69 

0.68 

 

0.43-1.1 

0.45-1.04 

Histological grade 

Grade1 (includes grade 

not assessed) 

Grade 2  

Grade 3 

 

64 

 

216 

259 

 

0.79 

 

0.77 

0.59 

 

0.24-2.6 

 

0.46-1.3 

0.39-0.9 

Menopausal status 

Pre-Menopausal  

Post-Menopausal  

 

285 

254 

 

0.64 

0.72 

 

0.40-1 

0.47-1.12 



78 

*a hazard ratio (TAC/FAC) of less than 1 indicates that TAC is associated with a longer disease free 

survival compared to FAC. 

 

Exploratory subgroup analyses for disease-free survival for patients who meet the 2009 St. Gallen 

chemotherapy criteria – (ITT population) were performed and presented here below 

 
 TAC 

 

FAC 

 

Hazard ratio 

(TAC/FAC) 

 

 

Subgroups (n=539) (n=521) (95% CI) p-value 

Meeting relative 

 indication 

for chemotherapya 

    

No 18/214 

(8.4%) 

26/227 

(11.5%) 

0.796 

(0.434 - 1.459) 

0.4593 

Yes 48/325 

(14.8%) 

69/294 

(23.5%) 

0.606 

(0.42 - 0.877) 

0.0072 

TAC = docetaxel, doxorubicin and cyclophosphamide 

FAC = 5-fluorouracil, doxorubicin and cyclophosphamide 

CI = confidence interval 

ER = oestrogen receptor 

PR = progesterone receptor 
a ER/PR-negative or Grade 3 or tumour size > 5 cm 

 

The estimated hazard ratio was using Cox proportional hazard model with treatment group as the 

factor. 

 

DOCETAXEL KABI as single agent 

 

Two randomised phase III comparative studies, involving a total of 326 alkylating or 

392 anthracycline failure metastatic breast cancer patients, have been performed with docetaxel at the 

recommended dose and regimen of 100 mg/m² every 3 weeks. 

 

In alkylating-failure patients, docetaxel was compared to doxorubicin (75 mg/m² every 3 weeks). 

Without affecting overall survival time (docetaxel 15 months vs. doxorubicin 14 months, p = 0.38) or 

time to progression (docetaxel 27 weeks vs. doxorubicin 23 weeks, p = 0.54), docetaxel increased 

response rate (52% vs. 37%, p = 0.01) and shortened time to response (12 weeks vs. 23 weeks, 

p= 0.007). Three docetaxel patients (2%) discontinued the treatment due to fluid retention, whereas 

15 doxorubicin patients (9%) discontinued due to cardiac toxicity (three cases of fatal congestive heart 

failure). 

 

In anthracycline-failure patients, docetaxel was compared to the combination of mitomycin C and 

vinblastine (12 mg/m² every 6 weeks and 6 mg/m² every 3 weeks). Docetaxel increased response rate 

(33% vs. 12%, p < 0.0001), prolonged time to progression (19 weeks vs. 11 weeks, p= 0.0004) and 

prolonged overall survival (11 months vs. 9 months, p= 0.01). 

 

During these two phase III studies, the safety profile of docetaxel was consistent with the safety profile 

observed in phase II studies (see section 4.8). 

 

An open-label, multi-centre, randomised phase III study was conducted to compare docetaxel 
monotherapy and paclitaxel in the treatment of advanced breast cancer in patients whose previous 

therapy should have included an anthracycline. A total of 449 patients were randomised to receive 
either docetaxel monotherapy 100 mg/m² as a 1 hour infusion or paclitaxel 175 mg/m² as a 3 hour 

infusion. Both regimens were administered every 3 weeks. 

Without affecting the primary endpoint, overall response rate (32% vs 25%, p = 0.10), docetaxel 

prolonged median time to progression (24.6 weeks vs 15.6 weeks; p < 0.01) and median survival 

(15.3 months vs 12.7 months; p = 0.03). 



79 

More grade 3/4 adverse events were observed for docetaxel monotherapy (55.4%) compared to 

paclitaxel (23.0%). 

 

DOCETAXEL KABI in combination with doxorubicin 

 

One large randomised phase III study, involving 429 previously untreated patients with metastatic 
disease, has been performed with doxorubicin (50 mg/m²) in combination with docetaxel (75 mg/m²) 

(AT arm) versus doxorubicin (60 mg/m²) in combination with cyclophosphamide (600 mg/m²) (AC 

arm). Both regimens were administered on day 1 every 3 weeks.  

 

• Time to progression (TTP) was significantly longer in the AT arm versus AC arm, p = 0.0138. 
The median TTP was 37.3 weeks (95% CI: 33.4 - 42.1) in AT arm and 31.9 weeks (95% CI: 27.4 - 

36.0) in AC arm.  

• Overall response rate (ORR) was significantly higher in the AT arm versus AC arm, p = 0.009. 
The ORR was 59.3% (95% CI: 52.8 - 65.9) in AT arm versus 46.5% (95% CI: 39.8 - 53.2) in AC 

arm.  

 

In this study, AT arm showed a higher incidence of severe neutropenia (90% versus 68.6%), febrile 

neutropenia (33.3% versus 10%), infection (8% versus 2.4%), diarrhoea (7.5% versus 1.4%), asthenia 

(8.5% versus 2.4%), and pain (2.8% versus 0%) than AC arm. On the other hand, AC arm showed a 

higher incidence of severe anaemia (15.8% versus 8.5%) than AT arm, and, in addition, a higher 

incidence of severe cardiac toxicity: congestive heart failure (3.8% versus 2.8%), absolute LVEF 

decrease ≥ 20% (13.1% versus 6.1%), absolute LVEF decrease ≥ 30% (6.2% versus 1.1%). Toxic 

deaths occurred in 1 patient in the AT arm (congestive heart failure) and in 4 patients in the AC arm 

(1 due to septic shock and 3 due to congestive heart failure).  

In both arms, quality of life measured by the EORTC questionnaire was comparable and stable during 

treatment and follow-up.  

 

DOCETAXEL KABI in combination with trastuzumab 

 

Docetaxel in combination with trastuzumab was studied for the treatment of patients with metastatic 

breast cancer whose tumours overexpress HER2, and who previously had not received chemotherapy 

for metastatic disease. One hundred eighty six patients were randomised to receive docetaxel 
(100 mg/m2) with or without trastuzumab; 60% of patients received prior anthracycline-based adjuvant 

chemotherapy. Docetaxel plus trastuzumab was efficacious in patients whether or not they had 

received prior adjuvant anthracyclines. The main test method used to determine HER2 positivity in 

this pivotal study was immunohistochemistry (IHC). A minority of patients were tested using 

fluorescence in-situ hybridization (FISH). In this study, 87% of patients had disease that was IHC 3+, 

and 95% of patients entered had disease that was IHC 3+ and/or FISH positive. Efficacy results are 

summarized in the following table:  

 

Parameter Docetaxel plus trastuzumab1 

n = 92 

Docetaxel1 

n = 94 

Response rate 

(95% CI) 

61% 

(50-71) 

34% 

(25-45) 

Median duration of response 

(months) 

(95% CI)  

11.4 

(9.2-15.0) 

5.1 

(4.4-6.2) 

Median TTP (months) 

(95% CI) 

10.6 

(7.6-12.9) 

5.7 

(5.0-6.5) 

Median survival (months) 

(95% CI) 

30.52 

(26.8-ne) 

22.12 

(17.6-28.9) 

TTP = time to progression; “ne” indicates that it could not be estimated or it was not yet reached.  
1Full analysis set (intent-to-treat)  



80 

2 Estimated median survival  

 

DOCETAXEL KABI in combination with capecitabine 

 

Data from one multi-centre, randomised, controlled phase III clinical study support the use of 
docetaxel in combination with capecitabine for treatment of patients with locally advanced or 

metastatic breast cancer after failure of cytotoxic chemotherapy, including an anthracycline. In this 

study, 255 patients were randomised to treatment with docetaxel (75 mg/m2 as a 1 hour intravenous 

infusion every 3 weeks) and capecitabine (1250 mg/m2 twice daily for 2 weeks followed by 1-week 

rest period). 256 patients were randomised to treatment with docetaxel alone (100 mg/m2 as a 1 hour 

intravenous infusion every 3 weeks). Survival was superior in the docetaxel + capecitabine 

combination arm (p = 0.0126). Median survival was 442 days (docetaxel + capecitabine) vs. 352 days 

(docetaxel alone). The overall objective response rates in the all-randomised population (investigator 

assessment) were 41.6% (docetaxel + capecitabine) vs. 29.7% (docetaxel alone); p = 0.0058. Time to 

progressive disease was superior in the docetaxel + capecitabine combination arm (p < 0.0001). The 

median time to progression was 186 days (docetaxel + capecitabine) vs. 128 days (docetaxel alone). 

 

Non-small cell lung cancer 

 

Patients previously treated with chemotherapy with or without radiotherapy 

 

In a phase III study, in previously treated patients, time to progression (12.3 weeks versus 7 weeks) 

and overall survival were significantly longer for docetaxel at 75 mg/m² compared to Best Supportive 

Care. The 1-year survival rate was also significantly longer in docetaxel (40%) versus BSC (16%). 

There was less use of morphinic analgesic (p < 0.01), non-morphinic analgesics (p < 0.01), other 

disease-related medicinal products (p = 0.06) and radiotherapy (p < 0.01) in patients treated with 

docetaxel at 75 mg/m² compared to those with BSC.  

The overall response rate was 6.8% in the evaluable patients, and the median duration of response was 

26.1 weeks.  

 

DOCETAXEL KABI in combination with platinum agents in chemotherapy-naïve patients 

 

In a phase III study, 1218 patients with unresectable stage IIIB or IV NSCLC, with KPS of 70% or 

greater, and who did not receive previous chemotherapy for this condition, were randomised to either 

docetaxel (T) 75 mg/m2 as a 1 hour infusion immediately followed by cisplatin (Cis) 75 mg/m2 over 

30-60 minutes every 3 weeks (TCis), docetaxel 75 mg/m2 as a 1 hour infusion in combination with 

carboplatin (AUC 6 mg/ml.min) over 30-60 minutes every 3 weeks, or vinorelbine (V) 25 mg/m2 

administered over 6-10 minutes on days 1, 8, 15, 22 followed by cisplatin 100 mg/m2 administered on 

day 1 of cycles repeated every 4 weeks (VCis).  

 

Survival data, median time to progression and response rates for two arms of the study are illustrated 

in the following table:  

 

 TCis 

n = 408 

VCis 

n = 404 

Statistical analysis 

Overall survival 

(Primary end-point): 

   

Median survival (months) 11.3 10.1 Hazard Ratio: 1.122 

 [97.2% CI: 0.937; 1.342]* 

1-year Survival (%) 46 41 Treatment difference: 5.4% 

[95% CI: -1.1; 12.0] 

2 year Survival (%) 21 14 Treatment difference: 6.2% 

[95% CI: 0.2; 12.3] 

Median time to progression 

(weeks): 

22.0 23.0 Hazard Ratio: 1.032  

[95% CI: 0.876; 1.216] 

Overall response rate (%): 31.6 24.5 Treatment difference: 7.1% 

[95% CI: 0.7; 13.5] 



81 

*: Corrected for multiple comparisons and adjusted for stratification factors (stage of disease and 

region of treatment), based on evaluable patient population. 

 

Secondary end-points included change of pain, global rating of quality of life by EuroQoL-5D, Lung 

Cancer Symptom Scale, and changes in Karnosfky performance status. Results on these end-points 

were supportive of the primary end-points results.  

 

For docetaxel/carboplatin combination, neither equivalent nor non-inferior efficacy could be proven 

compared to the reference treatment combination VCis.  

 

Prostate cancer 

Metastatic castration-resistant prostate cancer 

 

The safety and efficacy of docetaxel in combination with prednisone or prednisolone in patients with 

metastatic castration-resistant prostate cancer were evaluated in a randomised multi-centre phase III 

study (TAX 327). A total of 1006 patients with KPS ≥ 60 were randomised to the following treatment 

groups:  

• Docetaxel 75 mg/m2 every 3 weeks for 10 cycles. 

• Docetaxel 30 mg/m2 administered weekly for the first 5 weeks in a 6 week cycle for 5 cycles. 

• Mitoxantrone 12 mg/m2 every 3 weeks for 10 cycles. 
All 3 regimens were administered in combination with prednisone or prednisolone 5 mg twice daily, 

continuously. 

 

Patients who received docetaxel every three weeks demonstrated significantly longer overall survival 

compared to those treated with mitoxantrone. The increase in survival seen in the docetaxel weekly 

arm was not statistically significant compared to the mitoxantrone control arm. Efficacy endpoints for 

the docetaxel arms versus the control arm are summarized in the following table:  

 

Endpoint 

 

Docetaxel every 3 

weeks 

Docetaxel every 

week 

Mitoxantrone 

every 3 weeks 

Number of patients 

Median survival (months) 

95% CI 

Hazard ratio 

95% CI 

p-value† * 

335 

18.9 

(17.0-21.2) 

0.761 

(0.619-0.936) 

0.0094 

334 

17.4 

(15.7-19.0) 

0.912 

(0.747-1.113) 

0.3624 

337 

16.5 

(14.4-18.6) 

- 

- 

- 

Number of patients 

PSA** response rate (%) 

95% CI 

p-value* 

291 

45.4 

(39.5-51.3) 

0.0005 

282 

47.9 

(41.9-53.9) 

< 0.0001 

300 

31.7 

(26.4-37.3) 

- 

Number of patients 

Pain response rate (%) 

95% CI 

p-value* 

153 

34.6 

(27.1-42.7) 

0.0107 

154 

31.2 

(24.0-39.1) 

0.0798 

157 

21.7 

(15.5-28.9) 

- 

Number of patients 

Tumor response rate (%) 

95% CI 

p-value* 

141 

12.1 

(7.2-18.6) 

0.1112 

134 

8.2 

(4.2-14.2) 

0.5853 

137 

6.6 

(3.0-12.1) 

- 
†Stratified log-rank test  

*Threshold for statistical significance = 0.0175  

**PSA: Prostate-Specific Antigen  

 

Given the fact that docetaxel every week presented a slightly better safety profile than docetaxel every 

3 weeks, it is possible that certain patients may benefit from docetaxel every week.  



82 

 

No statistical differences were observed between treatment groups for Global Quality of Life. 

 

Metastatic hormone-sensitive prostate cancer 

 

STAMPEDE study 

 

The safety and efficacy of docetaxel administered concomitantly with standard of care (ADT) in 

patients with high-risk locally advanced or metastatic hormone-sensitive prostate cancer were 

evaluated in a randomised multi-centre, multi-arm multi-stage (MAMS) study with a seamless phase 

II/III design (STAMPEDE – MRC PR08). A total of 1776 male patients were allocated to the 
treatment arms of interest:  

• Standard of care + docetaxel 75 mg/m², administered every 3 weeks for 6 cycles 

• Standard of care alone  

Docetaxel regimen was administered in combination with prednisone or prednisolone 5 mg twice daily 

continuously.  

Among the 1776 randomised patients 1086 (61%) had metastatic disease, 362 were randomised to 

docetaxel in combination with standard of care, 724 received standard of care alone.  

 

In these metastatic prostate cancer patients, the median overall survival was significantly longer in 

docetaxel treatment groups than in the standard of care alone group, with a median overall survival 19 

months longer with the addition of docetaxel to standard of care (HR =  0.76, 95% CI = 0.62-0.92, 

p=0.005).  

 

Efficacy results in metastatic prostate cancer patients for docetaxel arm versus control arm are 

summarized in the following table: 

 

Efficacy of docetaxel in combination with prednisone or prednisolone and standard of care in the 

treatment of patients with metastatic hormone-sensitive prostate cancer (STAMPEDE) 

 

Endpoint 

 

Docetaxel + standard of care 

 

Standard of care alone 

Number of metastatic prostate 

cancer patients 

 

Median overall survival (months)  

95% CI 

362 

 

 

62 

51-73 

724 

 

 

43 

40-48 

Adjusted hazard ratio 

95% CI 

p-valuea 

0.76 

(0.62-0.92) 

0.005 

Failure-Free survivalb    

Median (months) 

95% CI 

20.4 

16.8-25.2 

12 

9.6-12 

Adjusted hazard ratio 

95% CI 

p-valuea 

0.66 

(0.57-0.76) 

< 0.001 

a p-value calculated from the likelihood ratio test and adjusted for all stratification factors 

(except center and planned hormone therapy) and stratified by trial period 
b Failure-free survival: time from randomization to first evidence of at least one of: biochemical 

failure (defined as a rise in PSA of 50% above the within-24-week nadir and above 4 ng/mL 

and confirmed by retest or treatment); progression either locally, in lymph nodes, or in distant 

metastases; skeletal-related event; or death from prostate cancer. 

 



83 

CHAARTED study 

 

The safety and efficacy of docetaxel administered at the beginning of androgen-deprivation therapy 

(ADT) in patients with metastatic hormone-sensitive prostate cancer were evaluated in a randomised 

Phase III multi-centre study (CHAARTED). A total of 790 male patients were allocated to the 2 

treatment groups.  

• ADT + docetaxel 75 mg/m² given at the beginning of ADT, administered every 3 weeks 

for 6 cycles 

• ADT alone   

 

The median overall survival was significantly longer in docetaxel treatment group than in the ADT 

alone group, with a median overall survival 13.6 months longer with the addition of docetaxel to ADT 

(hazard ratio (HR) = 0.61, 95% confidence interval (CI) = 0.47-0.80, p=0.0003).  

 

Efficacy results or the docetaxel arm versus the control arm are summarized in the following table: 

 

Efficacy of docetaxel and ADT in the treatment of patients with metastatic hormone-sensitive prostate 

cancer (CHAARTED) 

 

Endpoint 

 

Docetaxel +ADT  

 

ADT alone 

Number of patients 

Median overall survival (months) 

All patients 

95% CIAdjusted hazard ratio 

397 

 

57.6 

49.1-72.8 

0.61 

393 

 

44.0 

34.4-49.1 

-- 

95% CI (0.47-0.80)  -- 

p-valuea 0.0003 -- 

Progression Free Survival 

Median (months) 

95% CI 

Adjusted hazard ratio 
95% CI 

p-value* 

 

19.8 

16.7-22.8 

0.60 

0.51-0.72 

P<0.0001 

 

11.6 

10.8-14.3 

-- 

-- 

-- 

PSA response** at 6 months – N(%) 

p-valuea* 

127 (32.0) 

<0.0001 

77 (19.6) 

-- 

PSA response** at 12 months – N(%) 

p-valuea* 

110 (27.7) 

<0.0001 

66 (16.8) 

-- 

Time to castration-resistant prostate cancerb   

Median (months)  

95% CI 

Adjusted hazard ratio 

20.2 

(17.2-23.6) 

0.61 

11.7 

(10.8-14.7) 

-- 

95% CI (0.51-0.72) -- 

p-valuea* <0.0001 -- 

Time to clinical progressionc    

Median (months)  33.0 19.8 

95% CI (27.3-41.2) (17.9-22.8) 

Adjusted hazard ratio 0.61 -- 

95% CI (0.50-0.75) -- 

p-valuea* <0.0001 -- 



84 

a Time to event variables: Stratified log-rank test.  

  Response rate variables: Fisher's Exact test  

* p-value for descriptive purpose. 

** PSA response: Prostate-Specific Antigen response: PSA level <0.2 ng/mL measured for two 

consecutive measurements at least 4 weeks apart. 

b Time to castration-resistant prostate cancer = time from randomization to PSA progression or 

clinical progression (i.e., increasing symptomatic bone metastases, progression per Response 

Evaluation Criteria in Solid Tumours (RECIST) criteria, or clinical deterioration due to cancer 

per the Investigator’s opinion), whichever occurred first. 
c The time to clinical progression = the time from randomization until clinical progression (i.e., 

increased symptoms of bone metastases; progression according to RECIST; or clinical deterioration 

due to cancer according to the investigator’s opinion). 

 

Gastric adenocarcinoma 

 

A multi-centre, open-label, randomised study, was conducted to evaluate the safety and efficacy of 
docetaxel for the treatment of patients with metastatic gastric adenocarcinoma, including 

adenocarcinoma of the gastroesophageal junction, who had not received prior chemotherapy for 

metastatic disease. A total of 445 patients with KPS > 70 were treated with either docetaxel (T) 

(75 mg/m2 on day 1) in combination with cisplatin (C) (75 mg/m2 on day 1) and 5-fluorouracil (F) 

(750 mg/m2 per day for 5 days) or cisplatin (100 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2 per 

day for 5 days). The length of a treatment cycle was 3 weeks for the TCF arm and 4 weeks for the CF 

arm. The median number of cycles administered per patient was 6 (with a range of 1-16) for the TCF 

arm compared to 4 (with a range of 1-12) for the CF arm. Time to progression (TTP) was the primary 

endpoint. The risk reduction of progression was 32.1% and was associated with a significantly longer 

TTP (p = 0.0004) in favour of the TCF arm. Overall survival was also significantly longer 

(p = 0.0201) in favour of the TCF arm with a risk reduction of mortality of 22.7%. Efficacy results are 

summarized in the following table: 

 

Efficacy of docetaxel in the treatment of patients with gastric adenocarcinoma 

 

Endpoint TCF 

n = 221 

CF 

n = 224 

Median TTP (months) 

(95% CI) 

Hazard ratio 

(95% CI) 

*p-value 

5.6 

(4.86-5.91) 

3.7 

(3.45-4.47) 

1.473 

(1.189-1.825) 

0.0004 

Median survival (months) 

(95% CI) 

2-year estimate (%) 

Hazard ratio 

(95% CI) 

*p-value 

9.2 

(8.38-10.58) 

18.4 

8.6 

(7.16-9.46) 

8.8 

1.293 

(1.041-1.606) 

0.0201 

Overall Response Rate (CR+PR) (%) 

p-value 

36.7 25.4 

0.0106 

Progressive Disease as Best Overall Response (%) 16.7 25.9 

*Unstratified logrank test  

 

Subgroup analyses across age, gender and race consistently favoured the TCF arm compared to the CF 

arm.  



85 

 

A survival update analysis conducted with a median follow-up time of 41.6 months no longer showed 

a statistically significant difference although always in favour of the TCF regimen and showed that the 

benefit of TCF over CF is clearly observed between 18 and 30 months of follow up.  

 

Overall, quality of life (QoL) and clinical benefit results consistently indicated improvement in favour 

of the TCF arm. Patients treated with TCF had a longer time to 5% definitive deterioration of global 

health status on the QLQ-C30 questionnaire (p = 0.0121) and a longer time to definitive worsening of 

Karnofsky performance status (p = 0.0088) compared to patients treated with CF. 

 

Head and neck cancer 

 

• Induction chemotherapy followed by radiotherapy (TAX323)  
The safety and efficacy of docetaxel in the induction treatment of patients with squamous cell 

carcinoma of the head and neck (SCCHN) was evaluated in a phase III, multi-centre, open-label, 
randomised study (TAX323). In this study, 358 patients with inoperable locally advanced SCCHN, 

and WHO performance status 0 or 1, were randomised to one of two treatment arms. Patients on the 

docetaxel arm received docetaxel (T) 75 mg/m2 followed by cisplatin (P) 75 mg/m2 followed by 

5-fluorouracil (F) 750 mg/m2 per day as a continuous infusion for 5 days. This regimen was 

administered every three weeks for 4 cycles in case at least a minor response (≥ 25% reduction in 

bidimensionally measured tumour size) was observed after 2 cycles. At the end of chemotherapy, with 

a minimal interval of 4 weeks and a maximal interval of 7 weeks, patients whose disease did not 

progress received radiotherapy (RT) according to institutional guidelines for 7 weeks (TPF/RT). 

Patients on the comparator arm received cisplatin (P) 100 mg/m2 followed by 5-fluorouracil (F) 

1000 mg/m2 per day for 5 days. This regimen was administered every three weeks for 4 cycles in case 

at least a minor response (≥ 25% reduction in bidimensionally measured tumour size) was observed 

after 2 cycles. At the end of chemotherapy, with a minimal interval of 4 weeks and a maximal interval 

of 7 weeks, patients whose disease did not progress received radiotherapy (RT) according to 

institutional guidelines for 7 weeks (PF/RT). Locoregional therapy with radiation was delivered either 

with a conventional fraction (1.8 Gy - 2.0 Gy once a day, 5 days per week for a total dose of 66 to 

70 Gy), or accelerated/hyperfractionated regimens of radiation therapy (twice a day, with a minimum 

interfraction interval of 6 hours, 5 days per week). A total of 70 Gy was recommended for accelerated 

regimens and 74 Gy for hyperfractionated schemes. Surgical resection was allowed following 

chemotherapy, before or after radiotherapy. Patients on the TPF arm received antibiotic prophylaxis 

with ciprofloxacin 500 mg orally twice daily for 10 days starting on day 5 of each cycle, or equivalent. 

The primary endpoint in this study, progression-free survival (PFS), was significantly longer in the 

TPF arm compared to the PF arm, p = 0.0042 (median PFS: 11.4 vs. 8.3 months respectively) with an 

overall median follow up time of 33.7 months. Median overall survival was also significantly longer in 

favour of the TPF arm compared to the PF arm (median OS: 18.6 vs. 14.5 months respectively) with a 

28% risk reduction of mortality, p = 0.0128. Efficacy results are presented in the table below:  

 

Efficacy of docetaxel in the induction treatment of patients with inoperable locally advanced SCCHN 

(Intent-to-Treat Analysis) 

 

Endpoint Docetaxel + 

Cis + 5-FU 

n = 177 

Cis + 5-FU 

 

n = 181 

Median progression free survival (months) 

(95% CI) 

Adjusted Hazard ratio 

(95% CI) 

*p-value 

11.4 

(10.1-14.0) 

8.3 

(7.4-9.1) 

0.70 

(0.55-0.89) 

0.0042 

Median survival (months) 

(95% CI) 

18.6 

(15.7-24.0) 

14.5 

(11.6-18.7) 



86 

Endpoint Docetaxel + 

Cis + 5-FU 

n = 177 

Cis + 5-FU 

 

n = 181 

Hazard ratio 

(95% CI) 

**p-value 

0.72 

(0.56-0.93) 

0.0128 

Best overall response to chemotherapy (%) 

(95% CI)  

***p-value 

67.8 

(60.4-74.6) 

53.6 

(46.0-61.0) 

0.006 

Best overall response to study treatment [chemotherapy 

+/- radiotherapy] (%) 

(95% CI)  

***p-value 

72.3 

(65.1-78.8) 

58.6 

(51.0-65.8) 

0.006 

 Median duration of response to chemotherapy ± 

radiotherapy (months) 

(95% CI)  

Hazard ratio 

(95% CI) 

**p-value 

n = 128 

15.7 

(13.4-24.6) 

n = 106 

11.7 

(10.2-17.4) 

0.72 

(0.52-0.99) 

0.0457 

A hazard ratio of less than 1 favours docetaxel + cisplatin + 5-FU 
*Cox model (adjustment for Primary tumour site, T and N clinical stages and PSWHO) 

**Logrank test  

*** Chi-square test  

Quality of life parameters 

 

Patients treated with TPF experienced significantly less deterioration of their Global health score 

compared to those treated with PF (p = 0.01, using the EORTC QLQ-C30 scale). 

 

Clinical benefit parameters 

 

The performance status scale, for head and neck (PSS-HN) subscales designed to measure 

understandability of speech, ability to eat in public, and normalcy of diet, was significantly in favour 

of TPF as compared to PF. 

Median time to first deterioration of WHO performance status was significantly longer in the TPF arm 

compared to PF. Pain intensity score improved during treatment in both groups indicating adequate 

pain management.  

 

• Induction chemotherapy followed by chemoradiotherapy (TAX324)  
The safety and efficacy of docetaxel in the induction treatment of patients with locally advanced 

squamous cell carcinoma of the head and neck (SCCHN) was evaluated in a randomised, multi-centre 
open-label, phase III, study (TAX324). In this study, 501 patients, with locally advanced SCCHN, and 

a WHO performance status of 0 or 1, were randomised to one of two arms. The study population 
comprised patients with technically unresectable disease, patients with low probability of surgical cure 

and patients aiming at organ preservation. The efficacy and safety evaluation solely addressed survival 

endpoints and the success of organ preservation was not formally addressed. Patients on the docetaxel 

arm received docetaxel (T) 75 mg/m² by intravenous infusion on day 1 followed by cisplatin (P) 

100 mg/m² administered as a 30-minute to three-hour intravenous infusion, followed by the continuous 

intravenous infusion of 5-fluorouracil (F) 1000 mg/m²/day from day 1 to day 4. The cycles were 

repeated every 3 weeks for 3 cycles. All patients who did not have progressive disease were to receive 

chemoradiotherapy (CRT) as per protocol (TPF/CRT). Patients on the comparator arm received 

cisplatin (P) 100 mg/m² as a 30-minute to three-hour intravenous infusion on day 1 followed by the 

continuous intravenous infusion of 5-fluorouracil (F) 1000 mg/m²/day from day 1 to day 5. The cycles 



87 

were repeated every 3 weeks for 3 cycles. All patients who did not have progressive disease were to 

receive CRT as per protocol (PF/CRT).  

Patients in both treatment arms were to receive 7 weeks of CRT following induction chemotherapy 

with a minimum interval of 3 weeks and no later than 8 weeks after start of the last cycle (day 22 to 

day 56 of last cycle). During radiotherapy, carboplatin (AUC 1.5) was given weekly as a one-hour 

intravenous infusion for a maximum of 7 doses. Radiation was delivered with megavoltage equipment 

using once daily fractionation (2 Gy per day, 5 days per week for 7 weeks, for a total dose of 

70-72 Gy). Surgery on the primary site of disease and/or neck could be considered at anytime 

following completion of CRT. All patients on the docetaxel-containing arm of the study received 

prophylactic antibiotics. The primary efficacy endpoint in this study, overall survival (OS) was 

significantly longer (log-rank test, p = 0.0058) with the docetaxel-containing regimen compared to PF 

(median OS: 70.6 versus 30.1 months respectively), with a 30% risk reduction in mortality compared 

to PF (hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.54-0.90) with an overall median 

follow up time of 41.9 months. The secondary endpoint, PFS, demonstrated a 29% risk reduction of 

progression or death and a 22 month improvement in median PFS (35.5 months for TPF and 13.1 for 

PF). This was also statistically significant with an HR of 0.71; 95% CI 0.56-0.90; log-rank test 

p = 0.004. Efficacy results are presented in the table below: 

 

Efficacy of docetaxel in the induction treatment of patients with locally advanced SCCHN (Intent-to-

Treat Analysis) 

Endpoint Docetaxel + Cis + 5-FU 

n = 255 

Cis + 5-FU 

n = 246 

Median overall survival (months) 

(95% CI) 

Hazard ratio: 

(95% CI) 

*p-value  

70.6 

(49.0-NA) 

30.1 

(20.9-51.5) 

0.70 

(0.54-0.90) 

0.0058 

Median PFS (months) 

(95% CI) 

Hazard ratio: 

(95% CI) 

**p-value  

35.5 

(19.3-NA) 

13.1 

(10.6-20.2) 

0.71 

(0.56 - 0.90) 

0.004 

Best overall response (CR + PR) to 

chemotherapy (%) 

(95% CI)  

***p-value 

71.8 

(65.8-77.2) 

64.2 

(57.9-70.2) 

0.070 

Best overall response (CR + PR) to study 

treatment [chemotherapy +/- 

chemoradiotherapy] (%) 

(95% CI) 

***p-value 

 

76.5 

(70.8-81.5) 

 

71.5 

(65.5-77.1) 

0.209 

A hazard ratio of less than 1 favours docetaxel + cisplatin + fluorouracil  

*un-adjusted log-rank test  

**un-adjusted log-rank test, not adjusted for multiple comparisons  

***Chi square test, not adjusted for multiple comparisons  

NA-not applicable 

 

 

 

 

 

 

 



88 

5.2 Pharmacokinetic properties 

 

Absorption 

 

The pharmacokinetics of docetaxel have been evaluated in cancer patients after administration of 20-

115 mg/m2 in phase I studies. The kinetic profile of docetaxel is dose independent and consistent with 

a three-compartment pharmacokinetic model with half lives for the α, β and γ phases of 4 min, 36 min 

and 11.1 h, respectively. The late phase is due, in part, to a relatively slow efflux of docetaxel from the 

peripheral compartment. 

 

Distribution 

 

Following the administration of a 100 mg/m2 dose given as a one-hour infusion a mean peak plasma 

level of 3.7 μg/ml was obtained with a corresponding AUC of 4.6 h.μg/ml. Mean values for total body 

clearance and steady-state volume of distribution were 21 l/h/m2 and 113 l, respectively. Inter 

individual variation in total body clearance was approximately 50%. Docetaxel is more than 95% 

bound to plasma proteins.  

 

Elimination 

 

A study of 14C-docetaxel has been conducted in three cancer patients. Docetaxel was eliminated in 

both the urine and faeces following cytochrome P450-mediated oxidative metabolism of the tert-butyl 

ester group, within seven days, the urinary and faecal excretion accounted for about 6% and 75% of 

the administered radioactivity, respectively. About 80% of the radioactivity recovered in faeces is 

excreted during the first 48 hours as one major inactive metabolite and 3 minor inactive metabolites 

and very low amounts of unchanged medicinal product. 

 

Special populations 

 

Age and gender 

 

A population pharmacokinetic analysis has been performed with docetaxel in 577 patients. 

Pharmacokinetic parameters estimated by the model were very close to those estimated from phase I 

studies. The pharmacokinetics of docetaxel were not altered by the age or sex of the patient. 

 

Hepatic impairment 

In a small number of patients (n = 23) with clinical chemistry data suggestive of mild to moderate liver 

function impairment (ALT, AST ≥ 1.5 times the ULN associated with alkaline phosphatase ≥ 2.5 

times the ULN), total clearance was lowered by 27% on average (see section 4.2). 

 

Fluid retention 

Docetaxel clearance was not modified in patients with mild to moderate fluid retention and there are 

no data available in patients with severe fluid retention. 

 

Combination therapy 

 

Doxorubicin 

When used in combination, docetaxel does not influence the clearance of doxorubicin and the plasma 

levels of doxorubicinol (a doxorubicin metabolite). The pharmacokinetics of docetaxel, doxorubicin 

and cyclophosphamide were not influenced by their co-administration.  

 

Capecitabine 

Phase I study evaluating the effect of capecitabine on the pharmacokinetics of docetaxel and vice versa 

showed no effect by capecitabine on the pharmacokinetics of docetaxel (Cmax and AUC) and no 

effect by docetaxel on the pharmacokinetics of a relevant capecitabine metabolite 5'-DFUR.  

 

 



89 

Cisplatin 

Clearance of docetaxel in combination therapy with cisplatin was similar to that observed following 

monotherapy. The pharmacokinetic profile of cisplatin administered shortly after docetaxel infusion is 

similar to that observed with cisplatin alone.  

 

Cisplatin and 5-fluorouracil 

The combined administration of docetaxel, cisplatin and 5-fluorouracil in 12 patients with solid 

tumours had no influence on the pharmacokinetics of each individual medicinal product.  

 

Prednisone and dexamethasone 

The effect of prednisone on the pharmacokinetics of docetaxel administered with standard 

dexamethasone premedication has been studied in 42 patients. 

 

Prednisone 

No effect of prednisone on the pharmacokinetics of docetaxel was observed. 

 

 

5.3  Preclinical safety data 

 

The carcinogenic potential of docetaxel has not been studied. 

 

Docetaxel has been shown to be mutagenic in the in vitro micronucleus and chromosome aberration 

test in CHO-K1 cells and in the in vivo micronucleus test in the mouse. However, it did not induce 

mutagenicity in the Ames test or the CHO/HGPRT gene mutation assay. These results are consistent 

with the pharmacological activity of docetaxel.  

 

It was shown that docetaxel was embryotoxic and fetotoxic in rats and rabbits. Undesirable effects on 

the testis observed in rodent toxicity studies suggest that docetaxel may impair male fertility. 

 

 

6. PHARMACEUTICAL PARTICULARS 
 

6.1 List of excipients 

 

Polysorbate 80 

Ethanol anhydrous 

Anhydrous citric acid (pH adjustment) 

 

 

6.2 Incompatibilities 

 

This medicinal product must not be mixed with other medicinal products except those mentioned in 

section 6.6. 

 

 

6.3 Shelf life 

 

Unopened vial 

2 years. 

 

After opening of the vial 

Each vial is for single use and should be used immediately after opening. If not used immediately, 

in-use storage times and conditions are the responsibility of the user. 

 

 

 

 



90 

Once added to the infusion bag 

From a microbiological point of view, reconstitution/dilution must take place in controlled and aseptic 

conditions and the medicinal product should be used immediately. If not used immediately, in-use 

storage times and conditions are the responsibility of the user. 

 

Once added as recommended into the infusion bag, the docetaxel infusion solution, if stored below 

25°C, is stable for 6 hours. It should be used within 6 hours (including the one hour infusion 

intravenous administration). 

In addition, physical and chemical in-use stability of the infusion solution prepared as recommended 

has been demonstrated in non-PVC bags up to 48 hours when stored between 2 to 8°C. 

 

 

6.4 Special precautions for storage 

 

Do not store above 25°C.  

Store in the original package in order to protect from light.  

 

For storage conditions of the diluted medicinal product, see section 6.3. 

 

 

6.5 Nature and contents of container 

 

6 ml clear, colourless Type-I glass vial, closed with flurotec rubber stopper and a blue flip-off 

aluminium over seal containing 4 ml of concentrate. 

 

Each box contains one vial. 

 

 

6.6 Special precautions for disposal and other handling 

 

DOCETAXEL KABI is an antineoplastic agent and, as with other potentially toxic compounds, 

caution should be exercised when handling it and preparing the solution. The use of gloves is 

recommended. 

 

If DOCETAXEL KABI concentrate or infusion solution should come into contact with skin, wash 

immediately and thoroughly with soap and water. If DOCETAXEL KABI concentrate or infusion 

solution should come into contact with mucous membranes, wash immediately and thoroughly with 

water. 

 

Preparation for the intravenous administration 

 

Preparation of the infusion solution 

DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 

with this medicinal product (DOCETAXEL KABI 80 mg/4 ml concentrate for solution for 

infusion, which contains only 1 vial). 

 

DOCETAXEL KABI 80 mg/4 ml concentrate for solution for infusion requires NO prior 

dilution with a solvent and is ready to add to the infusion solution. 

 

Each vial is for single use and should be used immediately. 

 

If the vials are stored under refrigeration, allow the required number of boxes of DOCETAXEL KABI 

concentrate for solution for infusion to stand below 25°C for 5 minutes before use. More than one vial 

of DOCETAXEL KABI concentrate for solution for infusion may be necessary to obtain the required 

dose for the patient. Aseptically withdraw the required amount of DOCETAXEL KABI concentrate 

for solution for infusion using a calibrated syringe.  

 



91 

In DOCETAXEL KABI 80 mg/4 ml vial the concentration of docetaxel is 20 mg/ml. 

The required volume of DOCETAXEL KABI concentrate for solution for infusion must be injected 

via a single injection (one shot) into a 250 ml infusion bag or bottle containing either 5% glucose 

solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. 

 

If a dose greater than 190 mg of docetaxel is required, use a larger volume of the infusion vehicle so 

that a concentration of 0.74 mg/ml docetaxel is not exceeded. 

 

Mix the infusion bag or bottle manually using a rocking motion. 

 

The infusion bag solution should be used within 6 hours below 25°C including the one hour infusion 

to the patient. 

 

As with all parenteral products, DOCETAXEL KABI infusion solution should be visually inspected 

prior to use, and solutions containing a precipitate should be discarded. 

 

Docetaxel infusion solution is supersaturated, therefore may crystallize over time. If crystals appear, 

the solution must no longer be used and shall be discarded. 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

 

Fresenius Kabi Deutschland GmbH 

Else-Kröner-Straße 1, 

61352 Bad Homburg v.d.Höhe 

Germany 

 

 

8. MARKETING AUTHORISATION NUMBER 
 

EU/1/12/770/001 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 22nd May 2012 

Date of latest renewal: 23 February 2017 

 

 

10. DATE OF REVISION OF THE TEXT 
 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu  



92 

1. NAME OF THE MEDICINAL PRODUCT 
 

DOCETAXEL KABI 120 mg/6 ml concentrate for solution for infusion 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each ml of concentrate contains 20 mg docetaxel anhydrous. 

 

One vial of 6 ml of concentrate contains 120 mg of docetaxel. 

 

Excipient with known effect 

Each vial of concentrate contains 3 ml of ethanol anhydrous (2.37 g). 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Concentrate for solution for infusion (sterile concentrate). 

 

The concentrate is a clear, colourless to pale yellow solution. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 

 

Breast cancer 

 

DOCETAXEL KABI in combination with doxorubicin and cyclophosphamide is indicated for the 

adjuvant treatment of patients with: 

• operable node-positive breast cancer 

• operable node-negative breast cancer. 
 

For patients with operable node-negative breast cancer, adjuvant treatment should be restricted to 

patients eligible to receive chemotherapy according to internationally established criteria for primary 

therapy of early breast cancer (see section 5.1). 

DOCETAXEL KABI in combination with doxorubicin is indicated for the treatment of patients with 

locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for 

this condition. 

 

DOCETAXEL KABI monotherapy is indicated for the treatment of patients with locally advanced or 

metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have 

included an anthracycline or an alkylating agent. 

 

DOCETAXEL KABI in combination with trastuzumab is indicated for the treatment of patients with 

metastatic breast cancer whose tumours over express HER2 and who previously have not received 

chemotherapy for metastatic disease. 

 

DOCETAXEL KABI in combination with capecitabine is indicated for the treatment of patients with 

locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy 

should have included an anthracycline. 



93 

Non-small cell lung cancer 

 

DOCETAXEL KABI is indicated for the treatment of patients with locally advanced or metastatic 

non-small cell lung cancer after failure of prior chemotherapy. 

 

DOCETAXEL KABI in combination with cisplatin is indicated for the treatment of patients with 

unresectable, locally advanced or metastatic non-small cell lung cancer, in patients who have not 

previously received chemotherapy for this condition. 

 

Prostate cancer 

 

DOCETAXEL KABI in combination with prednisone or prednisolone is indicated for the treatment of 

patients with castration-resistant metastatic prostate cancer. 

 

DOCETAXEL KABI in combination with androgen-deprivation therapy (ADT), with or without 

prednisone or prednisolone, is indicated for the treatment of patients with metastatic hormone-

sensitive prostate cancer. 

 

Gastric adenocarcinoma 

 

DOCETAXEL KABI in combination with cisplatin and 5-fluorouracil is indicated for the treatment of 

patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal 

junction, who have not received prior chemotherapy for metastatic disease. 

 

Head and neck cancer 

 

DOCETAXEL KABI in combination with cisplatin and 5-fluorouracil is indicated for the induction 

treatment of patients with locally advanced squamous cell carcinoma of the head and neck. 

 

 

4.2 Posology and method of administration 

 

The use of docetaxel should be confined to units specialised in the administration of cytotoxic 

chemotherapy and it should only be administered under the supervision of a physician qualified in the 

use of anticancer chemotherapy (see section 6.6). 

 

 Posology 

For breast, non-small cell lung, gastric, and head and neck cancers, premedication consisting of an oral 

corticosteroid, such as dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to 

docetaxel administration, unless contraindicated, can be used (see section 4.4).  

For metastatic castration-resistant prostate cancer, given the concurrent use of prednisone or 

prednisolone the recommended premedication regimen is oral dexamethasone 8 mg, 12 hours, 3 hours 

and 1 hour before the docetaxel infusion (see section 4.4). 

For metastatic hormone-sensitive prostate cancer, irrespective of the concurrent use of prednisone or 

prednisolone, the recommended premedication regimen is oral dexamethasone 8 mg 12 hours, 3 hours, 

and 1 hour before docetaxel infusion (see section 4.4). 

 

Prophylactic G-CSF may be used to mitigate the risk of haematological toxicities. 

 

Docetaxel is administered as a one-hour infusion every three weeks.  

 

Breast cancer 

In the adjuvant treatment of operable node-positive and node-negative breast cancer, the recommended 

dose of docetaxel is 75 mg/m2 administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 

500 mg/m2 every 3 weeks for 6 cycles (TAC regimen) (see also Dose adjustments during treatment). 

For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose 



94 

of docetaxel is 100 mg/m2 in monotherapy. In first-line treatment, docetaxel 75 mg/m2 is given in 

combination therapy with doxorubicin (50 mg/m2). 

 

In combination with trastuzumab the recommended dose of docetaxel is 100 mg/m2 every three weeks, 

with trastuzumab administered weekly. In the pivotal study the initial docetaxel infusion was started 

the day following the first dose of trastuzumab. The subsequent docetaxel doses were administered 

immediately after completion of the trastuzumab infusion, if the preceding dose of trastuzumab was 

well tolerated. For trastuzumab dose and administration, see trastuzumab summary of product 

characteristics.  

 

In combination with capecitabine, the recommended dose of docetaxel is 75 mg/m2 every three weeks, 

combined with capecitabine at 1250 mg/m2 twice daily (within 30 minutes after a meal) for 2 weeks 

followed by 1-week rest period. For capecitabine dose calculation according to body surface area, see 

capecitabine summary of product characteristics.  

 

Non-small cell lung cancer 

In chemotherapy naïve patients treated for non-small cell lung cancer, the recommended dose regimen 

is docetaxel 75 mg/m2 immediately followed by cisplatin 75 mg/m2 over 30-60 minutes. For treatment 

after failure of prior platinum-based chemotherapy, the recommended dose is 75 mg/m² as a single 

agent. 

 

Prostate cancer 

Prostate cancer Metastatic castration-resistant prostate cancer  
The recommended dose of docetaxel is 75 mg/m2. Prednisone or prednisolone 5 mg orally twice daily 

is administered continuously (see section 5.1). 

 

Metastatic hormone-sensitive prostate cancer 

The recommended dose of docetaxel is 75 mg/m2 every 3 weeks for 6 cycles. Prednisone or 

prednisolone 5 mg orally twice daily may be administered continuously. 

 

Gastric adenocarcinoma 

The recommended dose of docetaxel is 75 mg/m2 as a 1-hour infusion, followed by cisplatin 

75 mg/m2, as a 1- to 3- hour infusion (both on day 1 only), followed by 5-fluorouracil 750 mg/m2 per 

day given as a 24-hour continuous infusion for 5 days, starting at the end of the cisplatin infusion. 

Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and 

appropriate hydration for cisplatin administration. Prophylactic G-CSF should be used to mitigate the 

risk of haematological toxicities (see also Dose adjustments during treatment). 

 

Head and neck cancer 

Patients must receive premedication with antiemetics and appropriate hydration (prior to and after 

cisplatin administration). Prophylactic G-CSF may be used to mitigate the risk of haematological 

toxicities. All patients on the docetaxel-containing arm of the TAX 323 and TAX 324 studies, received 

prophylactic antibiotics. 

 

• Induction chemotherapy followed by radiotherapy (TAX 323) 
For the induction treatment of inoperable locally advanced squamous cell carcinoma of the head 

and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m2 as a 1 hour infusion 

followed by cisplatin 75 mg/m2 over 1 hour, on day one, followed by 5-fluorouracil as a 

continuous infusion at 750 mg/m2 per day for five days. This regimen is administered every 

3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy. 

 

• Induction chemotherapy followed by chemoradiotherapy (TAX 324) 
For the induction treatment of patients with locally advanced (technically unresectable, low 

probability of surgical cure, and aiming at organ preservation) squamous cell carcinoma of the 

head and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m2 as a 1 hour 

intravenous infusion on day 1, followed by cisplatin 100 mg/m2 administered as a 30-minute to 

3-hour infusion, followed by 5-fluorouracil 1000 mg/m2/day as a continuous infusion from day 1 



95 

to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, 

patients should receive chemoradiotherapy. 

 

For cisplatin and 5-fluorouracil dose modifications, see the corresponding summary of product 

characteristics. 

 

Dose adjustments during treatment 

 

General 

Docetaxel should be administered when the neutrophil count is ≥ 1,500 cells/mm3. 

In patients who experienced either febrile neutropenia, neutrophil count < 500 cells/mm3 for more than 

one week, severe or cumulative cutaneous reactions or severe peripheral neuropathy during docetaxel 

therapy, the dose of docetaxel should be reduced from 100 mg/m2 to 75 mg/m2 and/or from 75 to 

60 mg/m². If the patient continues to experience these reactions at 60 mg/m², the treatment should be 

discontinued. 

 

Adjuvant therapy for breast cancer 

Primary G-CSF prophylaxis should be considered in patients who receive docetaxel, doxorubicin and 

cyclophosphamide (TAC) adjuvant therapy for breast cancer. Patients who experience febrile 

neutropenia and/or neutropenic infection should have their docetaxel dose reduced to 60 mg/m² in all 

subsequent cycles (see sections 4.4 and 4.8). Patients who experience Grade 3 or 4 stomatitis should 

have their dose decreased to 60 mg/m². 

 

In combination with cisplatin 

For patients who are dosed initially at docetaxel 75 mg/m2 in combination with cisplatin and whose 

nadir of platelet count during the previous course of therapy is < 25,000 cells/mm3, or in patients who 

experience febrile neutropenia, or in patients with serious non-haematologic toxicities, the docetaxel 

dose in subsequent cycles should be reduced to 65 mg/m2. For cisplatin dose adjustments, see the 

corresponding summary of product characteristics.  

 

In combination with capecitabine 

• For capecitabine dose modifications, see capecitabine summary of product characteristics. 

• For patients developing the first appearance of  Grade 2 toxicity, which persists at the time of the 
next docetaxel/capecitabine treatment, delay treatment until resolved to Grade 0-1, and resume at 

100% of the original dose. 

• For patients developing the second appearance of Grade 2 toxicity, or the first appearance of 
Grade 3 toxicity, at any time during the treatment cycle, delay treatment until resolved to Grade 

0-1 and then resume treatment with docetaxel 55 mg/m². 

• For any subsequent appearances of toxicities, or any Grade 4 toxicities, discontinue the docetaxel 
dose. 

 

For trastuzumab dose modifications, see trastuzumab summary of product characteristics. 

 

In combination with cisplatin and 5-fluorouracil 

If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite 

G-CSF use, the docetaxel dose should be reduced from 75 to 60 mg/m2. If subsequent episodes of 

complicated neutropenia occur the docetaxel dose should be reduced from 60 to 45 mg/m2. In case of 

Grade 4 thrombocytopenia the docetaxel dose should be reduced from 75 to 60 mg/m2. Patients should 

not be retreated with subsequent cycles of docetaxel until neutrophils recover to a level 

>1,500 cells/mm3 and platelets recover to a level >100,000 cells/mm3. Discontinue treatment if these 

toxicities persist (see section 4.4). 

Recommended dose modifications for toxicities in patients treated with docetaxel in combination with 

cisplatin and 5-fluorouracil (5-FU): 

 

 

 



96 

Toxicity Dose adjustment 

Diarrhoea grade 3  First episode: reduce 5-FU dose by 20%. 

Second episode: then reduce docetaxel dose by 20%. 

Diarrhoea grade 4 First episode: reduce docetaxel and 5-FU doses by 20%. 

Second episode: discontinue treatment. 

Stomatitis/mucositis grade 3  First episode: reduce 5-FU dose by 20%. 

Second episode: stop 5-FU only, at all subsequent cycles. 

Third episode: reduce docetaxel dose by 20%. 

Stomatitis/mucositis grade 4 First episode: stop 5-FU only, at all subsequent cycles. 

Second episode: reduce docetaxel dose by 20%. 

 

For cisplatin and 5-fluorouracil dose adjustments, see the corresponding summary of product 

characteristics. 

 

In the pivotal SCCHN studies patients who experienced complicated neutropenia (including prolonged 

neutropenia, febrile neutropenia, or infection), it was recommended to use G-CSF to provide 

prophylactic coverage (eg, day 6-15) in all subsequent cycles. 

 

Special populations 

 

Patients with hepatic impairment 

Based on pharmacokinetic data with docetaxel at 100 mg/m² as single agent, patients who have both 

elevations of transaminase (ALT and/or AST) greater than 1.5 times the upper limit of the normal 

range (ULN) and alkaline phosphatase greater than 2.5 times the ULN, the recommended dose of 

docetaxel is 75 mg/m2 (see sections 4.4 and 5.2). For those patients with serum bilirubin > ULN and/or 

ALT and AST > 3.5 times the ULN associated with alkaline phosphatase > 6 times the ULN, no 

dose-reduction can be recommended and docetaxel should not be used unless strictly indicated. 

In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric 

adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST > 1.5 × ULN 

associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no 

dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No 

data are available in patients with hepatic impairment treated by docetaxel in combination in the other 

indications.  

 

Paediatric population 

The safety and efficacy of DOCETAXEL KABI in nasopharyngeal carcinoma in children aged 

1 month to less than 18 years have not yet been established. 

There is no relevant use of DOCETAXEL KABI in the paediatric population in the indications breast 

cancer, non-small cell lung cancer, prostate cancer, gastric carcinoma and head and neck cancer, not 

including type II and III less differentiated nasopharyngeal carcinoma. 

 

Elderly  

Based on a population pharmacokinetic analysis, there are no special instructions for use in the elderly. 

In combination with capecitabine, for patients 60 years of age or more, a starting dose reduction of 

capecitabine to 75% is recommended (see capecitabine summary of product characteristics). 

 

Method of administration 

For instructions on preparation and administration of the product, see section 6.6. 

 

 

4.3 Contraindications 

 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 



97 

Patients with baseline neutrophil count of < 1,500 cells/mm3. 

 

Patients with severe liver impairment (see sections 4.2 and 4.4). 

 

Contraindications for other medicinal products also apply, when combined with docetaxel. 

 

 

4.4 Special warnings and precautions for use 

 

For breast and non-small cell lung cancers, premedication consisting of an oral corticosteroid, such as 

dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to docetaxel 

administration, unless contraindicated, can reduce the incidence and severity of fluid retention as well 

as the severity of hypersensitivity reactions. For prostate cancer, the premedication is oral 

dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the docetaxel infusion (see section 4.2). 

 

Haematology 

 

Neutropenia is the most frequent adverse reaction of docetaxel. Neutrophil nadirs occurred at a median 

of 7 days but this interval may be shorter in heavily pre-treated patients. Frequent monitoring of 

complete blood counts should be conducted on all patients receiving docetaxel. Patients should be 

retreated with docetaxel when neutrophils recover to a level ≥ 1,500 cells/mm3 (see section 4.2). 

 

In the case of severe neutropenia (< 500 cells/mm3 for seven days or more) during a course of 

docetaxel therapy, a reduction in dose for subsequent courses of therapy or the use of appropriate 

symptomatic measures are recommended (see section 4.2). 

 

In patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (TCF), febrile 

neutropenia and neutropenic infection occurred at lower rates when patients received prophylactic 

G-CSF. Patients treated with TCF should receive prophylactic G-CSF to mitigate the risk of 

complicated neutropenia (febrile neutropenia, prolonged neutropenia or neutropenic infection). 

Patients receiving TCF should be closely monitored (see sections 4.2 and 4.8). 

 

In patients treated with docetaxel in combination with doxorubicin and cyclophosphamide (TAC), 

febrile neutropenia and/or neutropenic infection occurred at lower rates when patients received 

primary G-CSF prophylaxis. Primary G-CSF prophylaxis should be considered in patients who receive 

adjuvant therapy with TAC for breast cancer to mitigate the risk of complicated neutropenia (febrile 

neutropenia, prolonged neutropenia or neutropenic infection). Patients receiving TAC should be 

closely monitored (see sections 4.2 and 4.8). 

 

Gastrointestinal reactions 

 

Caution is recommended for patients with neutropenia, particularly at risk for developing 

gastrointestinal complications. Although majority of cases occurred during the first or second cycle of 

docetaxel containing regimen, enterocolitis could develop at any time, and could lead to death as early 

as on the first day of onset. Patients should be closely monitored for early manifestations of serious 

gastrointestinal toxicity (see sections 4.2, 4.4 Haematology, and 4.8). 

 

Hypersensitivity reactions 

 

Patients should be observed closely for hypersensitivity reactions especially during the first and 

second infusions. Hypersensitivity reactions may occur within a few minutes following the initiation 

of the infusion of docetaxel, thus facilities for the treatment of hypotension and bronchospasm should 

be available. If hypersensitivity reactions occur, minor symptoms such as flushing or localised 

cutaneous reactions do not require interruption of therapy. However, severe reactions, such as severe 

hypotension, bronchospasm or generalised rash/erythema require immediate discontinuation of 

docetaxel and appropriate therapy. Patients who have developed severe hypersensitivity reactions 

should not be re-challenged with docetaxel. Patients who have previously experienced a 



98 

hypersensitivity reaction to paclitaxel may be at risk to develop hypersensitivity reaction to docetaxel, 

including more severe hypersensitivity reaction. These patients should be closely monitored during 

initiation of docetaxel therapy. 

 

Cutaneous reactions 

 

Localised skin erythema of the extremities (palms of the hands and soles of the feet) with oedema 

followed by desquamation has been observed. Severe symptoms such as eruptions followed by 

desquamation which lead to interruption or discontinuation of docetaxel treatment were reported (see 

section 4.2). 

 

Severe Cutaneous Adverse Reactions (SCARs) such as Stevens-Johnson Syndrome (SJS), Toxic 

Epidermal Necrolysis (TEN) and Acute Generalized Exanthematous Pustulosis (AGEP) have been 

reported with docetaxel treatment. Patients should be informed about the signs and symptoms of 

serious skin manifestations and closely monitored. If signs and symptoms suggestive of these reactions 

appear discontinuation of docetaxel should be considered. 

 

Fluid retention 

 

Patients with severe fluid retention such as pleural effusion, pericardial effusion and ascites should be 

monitored closely. 

 

Respiratory disorders 

 

Acute respiratory distress syndrome, interstitial pneumonia/pneumonitis, interstitial lung disease, 

pulmonary fibrosis and respiratory failure have been reported and may be associated with fatal 

outcome. Cases of radiation pneumonitis have been reported in patients receiving concomitant 

radiotherapy. 

 

If new or worsening pulmonary symptoms develop, patients should be closely monitored, promptly 

investigated, and appropriately treated. Interruption of docetaxel therapy is recommended until 

diagnosis is available. Early use of supportive care measures may help improve the condition. The 

benefit of resuming docetaxel treatment must be carefully evaluated. 

 

Patients with liver impairment 

 

In patients treated with docetaxel at 100 mg/m2 as single agent who have serum transaminase levels 

(ALT and/or AST) greater than 1.5 times the ULN concurrent with serum alkaline phosphatase levels 

greater than 2.5 times the ULN, there is a higher risk of developing severe adverse reactions such as 

toxic deaths including sepsis and gastrointestinal haemorrhage which can be fatal, febrile neutropenia, 

infections, thrombocytopenia, stomatitis and asthenia. Therefore, the recommended dose of docetaxel 

in those patients with elevated liver function test (LFTs) is 75 mg/m2 and LFTs should be measured at 

baseline and before each cycle (see section 4.2). 

For patients with serum bilirubin levels > ULN and/or ALT and AST > 3.5 times the ULN concurrent 

with serum alkaline phosphatase levels > 6 times the ULN, no dose-reduction can be recommended 

and docetaxel should not be used unless strictly indicated. 

In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric 

adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST > 1.5 × ULN 

associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no 

dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No 

data are available in patients with hepatic impairment treated by docetaxel in combination in the other 

indications.  

 

Patients with renal impairment 

 

There are no data available in patients with severely impaired renal function treated with docetaxel. 

 



99 

Nervous system 

 

The development of severe peripheral neurotoxicity requires a reduction of dose (see section 4.2). 

 

Cardiac toxicity 

 

Heart failure has been observed in patients receiving docetaxel in combination with trastuzumab, 

particularly following anthracycline (doxorubicin or epirubicin)-containing chemotherapy. This may 

be moderate to severe and has been associated with death (see section 4.8). 

 

When patients are candidates for treatment with docetaxel in combination with trastuzumab, they 

should undergo baseline cardiac assessment. Cardiac function should be further monitored during 

treatment (e.g. every three months) to help identify patients who may develop cardiac dysfunction. For 

more details see summary of product characteristics of trastuzumab.  

 

Ventricular arrhythmia including ventricular tachycardia (sometimes fatal) has been reported in 

patients treated with docetaxel in combination regimens including doxorubicin, 5-fluorouracil and/ or 

cyclophosphamide (see section 4.8).  

Baseline cardiac assessment is recommended.   

 

Eye disorders 
 

Cystoid macular oedema (CMO) has been reported in patients treated with docetaxel. Patients with 

impaired vision should undergo a prompt and complete ophthalmologic examination. In case CMO is 

diagnosed, docetaxel treatment should be discontinued and appropriate treatment initiated (see section 

4.8). 

 

Second primary malignancies 

 

Second primary malignancies have been reported when docetaxel was given in combination with 

anticancer treatments known to be associated with second primary malignancies.  Second primary 

malignancies (including acute myeloid leukemia, myelodysplastic syndrome and non-Hodgkin 

lymphoma) may occur several months or years after docetaxel-containing therapy. Patients should be 

monitored for second primary malignancies (see section 4.8). 

 

Others 

 

Contraceptive measures must be taken by both men and women during treatment and for men at least 

6 months after cessation of therapy (see section 4.6). 

 

The concomitant use of docetaxel with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, 

clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and 

voriconazole) should be avoided (see section 4.5). 

 

Additional cautions for use in adjuvant treatment of breast cancer 

 

Complicated neutropenia 

For patients who experience complicated neutropenia (prolonged neutropenia, febrile neutropenia or 

infection), G-CSF and dose reduction should be considered (see section 4.2). 

 

Gastrointestinal reactions 

Symptoms such as early abdominal pain and tenderness, fever, diarrhoea, with or without neutropenia, 

may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated 

promptly. 

 

 

 



100 

Congestive heart failure (CHF) 

Patients should be monitored for symptoms of congestive heart failure during therapy and during the 

follow up period. In patients treated with the TAC regimen for node positive breast cancer, the risk of 

CHF has been shown to be higher during the first year after treatment (see sections 4.8 and 5.1). 

 

Patients with 4+ nodes 

As the benefit observed in patient with 4+ nodes was not statistically significant on disease-free 

survival (DFS) and overall survival (OS), the positive benefit/risk ratio for TAC in patients with 4+ 

nodes was not fully demonstrated at the final analysis (see section 5.1). 

 

Elderly  

Cautions for use in adjuvant treatment of breast cancer 

There are limited data available in patients > 70 years of age on docetaxel use in combination with 

doxorubicin and cyclophosphamide. 

 

Cautions for use in castration-resistant prostate cancer 

Of the 333 patients treated with docetaxel every three weeks in a prostate cancer study, 209 patients 

were 65 years of age or greater and 68 patients were older than 75 years. In patients treated with 

docetaxel every three weeks, the incidence of related nail changes occurred at a rate ≥ 10% higher in 

patients who were 65 years of age or greater compared to younger patients. The incidence of related 

fever, diarrhoea, anorexia, and peripheral oedema occurred at rates ≥ 10% higher in patients who were 

75 years of age or greater versus less than 65 years. 

 

Cautions for use in hormone-sensitive prostate cancer 

Of the 545 patients treated with docetaxel every 3 weeks in a hormone-sensitive prostate cancer study 

(STAMPEDE), 296 patients were 65 years of age or older, and 48 patients were 75 years of age or 

older. More patients aged ≥65 years in the docetaxel arm reported hypersensitivity reaction, 

neutropenia, anaemia, fluid retention, dyspnea, and nail changes when compared to the patients aged 

less than 65 years. None of these increases in frequency reached 10% difference with the control arm. 

In patients who were 75 years of age or older, when compared to younger patients, neutropenia, 

anaemia, diarrhea, dyspnea and upper respiratory tract infection were reported with a greater incidence 

(at least 10% higher).  

 

Cautions for use in gastric adenocarcinoma cancer 

Among the 300 (221 patients in the phase III part of the study and 79 patients in the phase II part) 

patients treated with docetaxel in combination with cisplatin and 5-fluorouracil in the gastric cancer 

study, 74 were 65 years of age or older and 4 patients were 75 years of age or older. The incidence of 

serious adverse events was higher in older people compared to younger patients. The incidence of the 

following adverse events (all grades): lethargy, stomatitis, neutropenic infection occurred at rates 

≥ 10% higher in patients who were 65 years of age or older compared to younger patients. 

Elderly treated with TCF should be closely monitored. 

 

Excipients 

 
This medicinal product contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 2.37 g ethanol 

anhydrous per vial of 6 ml equivalent to 60 ml of beer or 24 ml wine. 

Harmful for those suffering from alcoholism. 

To be taken into account in pregnant or breast-feeding women, children and high-risk groups 

such as patients with liver disease, or epilepsy. 
 

Consideration should be given to possible effects on the central nervous system. 

 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

The amount of alcohol in this medicinal product may alter the effects of other medicinal products. 



101 

In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant 

administration of compounds which induce, inhibit or are metabolised by (and thus may inhibit the 

enzyme competitively) cytochrome P450-3A such as ciclosporine, ketoconazole and erythromycin. As 

a result, caution should be exercised when treating patients with these medicinal products as 

concomitant therapy since there is a potential for a significant interaction. 

In case of combination with CYP3A4 inhibitors, the occurrence of docetaxel adverse reactions may 

increase, as a result of reduced metabolism. If the concomitant use of a strong CYP3A4 inhibitor (e.g., 

ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, 

telithromycin and voriconazole) cannot be avoided, a close clinical surveillance is warranted and a 

dose-adjustment of docetaxel may be suitable during the treatment with the strong CYP3A4 inhibitor 

(see section 4.4). In a pharmacokinetic study with 7 patients, the co-administration of docetaxel with 

the strong CYP3A4 inhibitor ketoconazole leads to a significant decrease in docetaxel clearance by 

49%. 

Docetaxel pharmacokinetics in the presence of prednisone was studied in patients with metastatic 

prostate cancer. Docetaxel is metabolised by CYP3A4 and prednisone is known to induce CYP3A4. 

No statistically significant effect of prednisone on the pharmacokinetics of docetaxel was observed. 

 

Docetaxel is highly protein bound (> 95%). Although the possible in vivo interaction of docetaxel with 

concomitantly administered medicinal product has not been investigated formally, in vitro interactions 

with tightly protein-bound agents such as erythromycin, diphenhydramine, propranolol, propafenone, 

phenytoin, salicylate, sulfamethoxazole and sodium valproate did not affect protein binding of 

docetaxel. In addition, dexamethasone did not affect protein binding of docetaxel. Docetaxel did not 

influence the binding of digitoxin. 

 

The pharmacokinetics of docetaxel, doxorubicin and cyclophosphamide were not influenced by their 

co-administration. Limited data from a single uncontrolled study were suggestive of an interaction 

between docetaxel and carboplatin. When combined to docetaxel, the clearance of carboplatin was 

about 50% higher than values previously reported for carboplatin monotherapy. 

 

 

4.6 Fertility, pregnancy and lactation 

 

Women of childbearing potential/ Contraception in males and females 

 

Women of childbearing age receiving docetaxel should be advised to avoid becoming pregnant, and to 

inform the treating physician immediately should this occur. An effective method of contraception 

should be used during treatment. 

 

Pregnancy 

 

There is no information on the use of docetaxel in pregnant women. Docetaxel has been shown to be 

both embryotoxic and foetotoxic in rabbits and rats, and to reduce fertility in rats (see section 5.3). As 

with other cytotoxic medicinal products, docetaxel may cause foetal harm when administered to 

pregnant women. Therefore, docetaxel must not be used during pregnancy unless clearly indicated.  

 

Breast-feeding 

 

Docetaxel is a lipophilic substance but it is not known whether it is excreted in human milk. 

Consequently, because of the potential for adverse reactions in nursing infants, breast feeding must be 

discontinued for the duration of docetaxel therapy. 

 

 

 

 

 



102 

Fertility 

 

In non clinical studies, docetaxel has genotoxic effects and may alter male fertility (see section 5.3). 

Therefore, men being treated with docetaxel are advised not to father a child during and up to 

6 months after treatment and to seek advice on conservation of sperm prior to treatment. 

 

 

4.7 Effects on ability to drive and use machines 

 

No studies on the effects on the ability to drive and use machines have been performed. The amount of 

alcohol in this medicinal product and the side effects of the product may impair the ability to drive or 

use machines (see sections 4.4 and 4.8). Therefore, patients should be warned of the potential impact 

of the amount of alcohol and the side effects of this medicinal product on the ability to drive or use 

machines, and be advised not to drive or use machines if they experience these side effects during 

treatment. 

 

 

4.8 Undesirable effects 

 

Summary of the safety profile for all indications 

 

The adverse reactions considered to be possibly or probably related to the administration of docetaxel 

have been obtained in: 

 

• 1,312 and 121 patients who received 100 mg/m² and 75 mg/m² of docetaxel as a single agent 
respectively. 

• 258 patients who received docetaxel in combination with doxorubicin. 

• 406 patients who received docetaxel in combination with cisplatin. 

• 92 patients treated with docetaxel in combination with trastuzumab. 

• 255 patients who received docetaxel in combination with capecitabine. 

• 332 patients (TAX327) who received docetaxel in combination with prednisone or prednisolone 
(clinically important treatment related adverse events are presented). 

• 1,276 patients (744 and 532 in TAX 316 and GEICAM 9805 respectively) who received 
docetaxel in combination with doxorubicin and cyclophosphamide (clinically important 

treatment related adverse events are presented). 

• 300 gastric adenocarcinoma patients (221 patients in the phase III part of the study and 
79 patients in the phase II part) who received docetaxel in combination with cisplatin and 

5-fluorouracil (clinically important treatment related adverse events are presented). 

• 174 and 251 head and neck cancer patients who received docetaxel in combination with 
cisplatin and 5-fluorouracil (clinically important treatment related adverse events are presented). 

• 545 patients (STAMPEDE study) who received docetaxel in combination with prednisone or 
prednisolone and ADT. 

 

These reactions were described using the NCI Common Toxicity Criteria (grade 3 = G3; 

grade 3-4 = G3/4; grade 4 = G4), the COSTART and the MedDRA terms. Frequencies are defined as: 
very common (≥ 1/10), common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare 

(≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from available 

data). 

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 

 

The most commonly reported adverse reactions of docetaxel alone are: neutropenia (which was 

reversible and not cumulative; the median day to nadir was 7 days and the median duration of severe 

neutropenia (< 500 cells/mm3) was 7 days), anaemia, alopecia, nausea, vomiting, stomatitis, diarrhoea 

and asthenia. The severity of adverse events of docetaxel may be increased when docetaxel is given in 

combination with other chemotherapeutic agents. 



103 

For combination with trastuzumab, adverse events (all grades) reported in ≥ 10% are displayed. There 

was an increased incidence of SAEs (40% vs. 31%) and Grade 4 AEs (34% vs. 23%) in the 

trastuzumab combination arm compared to docetaxel monotherapy. 

 

For combination with capecitabine, the most frequent treatment-related undesirable effects (≥ 5%) 

reported in a phase III study in breast cancer patients failing anthracycline treatment are presented (see 

capecitabine summary of product characteristics). 

 

For combination with ADT and with prednisone or prednisolone (STAMPEDE study), adverse events 

occurring occurring over the 6 cycles of treatment with docetaxel and having at least 2% higher 

incidence in the docetaxel treatment arm by comparison to the control arm, are presented, using the 

CTCAE grading scale. 

 

The following adverse reactions are frequently observed with docetaxel:  

 

Immune system disorders 

 

Hypersensitivity reactions have generally occurred within a few minutes following the start of the 

infusion of docetaxel and were usually mild to moderate. The most frequently reported symptoms 

were flushing, rash with or without pruritus, chest tightness, back pain, dyspnoea and fever or chills. 

Severe reactions were characterised by hypotension and/or bronchospasm or generalized 

rash/erythema (see section 4.4). 

 

Nervous system disorders 

 

The development of severe peripheral neurotoxicity requires a reduction of dose (see sections 4.2 and 

4.4). Mild to moderate neuro-sensory signs are characterised by paraesthesia, dysesthesia or pain 

including burning. Neuro-motor events are mainly characterised by weakness. 

 

Skin and subcutaneous tissue disorders 

 

Reversible cutaneous reactions have been observed and were generally considered as mild to 

moderate. Reactions were characterised by a rash including localised eruptions mainly on the feet and 

hands (including severe hand and foot syndrome), but also on the arms, face or thorax, and frequently 

associated with pruritus. Eruptions generally occurred within one week after the docetaxel infusion. 

Less frequently, severe symptoms such as eruptions followed by desquamation which rarely lead to 

interruption or discontinuation of docetaxel treatment were reported (see sections 4.2 and 4.4). Severe 

nail disorders are characterised by hypo- or hyperpigmentation and sometimes pain and onycholysis. 

 

General disorders and administration site conditions 

 

Infusion site reactions were generally mild and consisted of hyper pigmentation, inflammation, 

redness or dryness of the skin, phlebitis or extravasation and swelling of the vein.  

Fluid retention includes events such as peripheral oedema and less frequently pleural effusion, 

pericardial effusion, ascites and weight gain. The peripheral oedema usually starts at the lower 

extremities and may become generalised with a weight gain of 3 kg or more. Fluid retention is 

cumulative in incidence and severity (see section 4.4). 

 

Tabulated list of adverse reactions in breast cancer for DOCETAXEL KABI 100 mg/m² single agent 

 

MedDRA system 

organ classes 

Very common 

adverse reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infections 

(G3/4: 5.7%; including 

sepsis and pneumonia, 

fatal in 1.7%) 

Infection associated 

with G4 neutropenia 

(G3/4: 4.6%) 

  



104 

MedDRA system 

organ classes 

Very common 

adverse reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Blood and lymphatic 

system disorders 

Neutropenia 

(G4: 76.4%); 

Anaemia 

(G3/4: 8.9%); 

Febrile neutropenia 

Thrombocytopenia 

(G4: 0.2%) 

  

Immune system 

disorders 

Hypersensitivity 

(G3/4: 5.3%) 

    

Metabolism and 

nutrition disorders 

Anorexia     

Nervous system 

disorders 

Peripheral sensory 

neuropathy 

(G3: 4.1%); 

Peripheral motor 

neuropathy 

(G3/4: 4%); 

Dysgeusia 

(severe: 0.07%) 

    

Cardiac disorders   Arrhythmia 

(G3/4: 0.7%) 

Cardiac failure 

Vascular disorders   Hypotension; 

Hypertension; 

Haemorrhage 

  

Respiratory, thoracic 

and mediastinal 

disorders 

Dyspnoea 

(severe: 2.7%) 

    

Gastrointestinal 

disorders 

Stomatitis 

(G3/4: 5.3%); 

Diarrhoea (G3/4: 4%); 

Nausea (G3/4: 4%); 

Vomiting (G3/4: 3%) 

Constipation 

(severe: 0.2%); 

Abdominal pain 

(severe: 1%); 

Gastrointestinal 

haemorrhage 

(severe: 0.3%) 

Oesophagitis 

(severe: 0.4%) 

Skin and subcutaneous 

tissue disorders 

Alopecia; 

Skin reaction 

(G3/4: 5.9%); 

Nail disorders 

(severe: 2.6%) 

    

Musculoskeletal and 

connective tissue 

disorders 

Myalgia 

(severe: 1.4%) 

Arthralgia   

General disorders and 

administration site 

conditions 

Fluid retention 

(severe: 6.5%); 

Asthenia 

(severe: 11.2%); 

Pain 

Infusion site reaction;  

Non-cardiac chest pain 

(severe: 0.4%) 

  

Investigations   G3/4 Blood bilirubin 

increased (< 5%); 

G3/4 Blood alkaline 

  



105 

MedDRA system 

organ classes 

Very common 

adverse reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

phosphatase increased 

(< 4%);G3/4 AST 

increased (< 3%); 

G3/4 ALT increased 

(< 2%) 

 

Description of selected adverse reactions in breast cancer for DOCETAXEL KABI 100 mg/m² single 

agent 

 

Blood and lymphatic system disorders 

Rare: bleeding episodes associated with grade 3/4 thrombocytopenia.  

 

Nervous system disorders 

Reversibility data are available among 35.3% of patients who developed neurotoxicity following 

docetaxel treatment at 100 mg/m² as single agent. The events were spontaneously reversible within 

3 months. 

 

Skin and subcutaneous tissue disorders 

Very rare: one case of alopecia non-reversible at the end of the study. 73% of the cutaneous reactions 

were reversible within 21 days. 

 

General disorders and administration site conditions 

The median cumulative dose to treatment discontinuation was more than 1,000 mg/m2 and the median 

time to fluid retention reversibility was 16.4 weeks (range 0 to 42 weeks). The onset of moderate and 

severe retention is delayed (median cumulative dose: 818.9 mg/m2) in patients with premedication 

compared with patients without premedication (median cumulative dose: 489.7 mg/m2); however, it 

has been reported in some patients during the early courses of therapy. 

 

Tabulated list of adverse reactions in  non-small lung cancer for DOCETAXEL KABI 75 mg/m² 

single agent 

 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Infections and infestations Infections (G3/4: 5%)   

Blood and lymphatic system 

disorders 

Neutropenia (G4: 54.2%); 

Anaemia (G3/4: 10.8%); 

Thrombocytopenia (G4: 1.7%) 

Febrile neutropenia 

Immune system disorders   Hypersensitivity (no severe) 

Metabolism and nutrition 

disorders 

Anorexia   

Nervous system disorders Peripheral sensory neuropathy 

(G3/4: 0.8%) 

Peripheral motor neuropathy 

(G3/4: 2.5%) 

Cardiac disorders   Arrhythmia (no severe) 

Vascular disorders   Hypotension 

Gastrointestinal disorders Nausea (G3/4: 3.3%); 

Stomatitis (G3/4: 1.7%); 

Vomiting (G3/4: 0.8%); 

Diarrhoea (G3/4: 1.7%) 

Constipation 



106 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Skin and subcutaneous tissue 

disorders 

Alopecia; 

Skin reaction (G3/4: 0.8%) 

Nail disorders (severe: 0.8%) 

Musculoskeletal and 

connective tissue disorders 

  Myalgia 

General disorders and 

administration site conditions 

Asthenia (severe: 12.4%); 

Fluid retention 

(severe: 0.8%);Pain 

  

Investigations   G3/4 Blood bilirubin 

increased (< 2%) 

 

Tabulated list of adverse reactions in breast cancer for DOCETAXEL KABI 75 mg/m² in combination 

with doxorubicin 

 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 7.8%)     

Blood and lymphatic 

system disorders 

Neutropenia 

(G4: 91.7%); 

Anaemia (G3/4: 9.4%); 

Febrile neutropenia; 

Thrombocytopenia 

(G4: 0.8%) 

    

Immune system 

disorders 

  Hypersensitivity 

(G3/4: 1.2%) 

  

Metabolism and 

nutrition disorders 

  Anorexia   

Nervous system 

disorders 

Peripheral sensory 

neuropathy (G3: 0.4%) 

Peripheral motor 

neuropathy 

(G3/4: 0.4%) 

  

Cardiac disorders   Cardiac failure; 

Arrhythmia (no 

severe) 

  

Vascular disorders     Hypotension 

Gastrointestinal 

disorders 

Nausea (G3/4: 5%); 

Stomatitis 

(G3/4: 7.8%); 

Diarrhoea 

(G3/4: 6.2%); 

Vomiting (G3/4: 5%); 

Constipation 

    

Skin and subcutaneous 

tissue disorders 

Alopecia; 

Nail disorders 

(severe: 0.4%); 

Skin reaction (no 

severe) 

    



107 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Musculoskeletal and 

connective tissue 

disorders 

  Myalgia   

General disorders and 

administration site 

conditions 

Asthenia 

(severe: 8.1%); 

Fluid retention 

(severe: 1.2%); 

Pain 

Infusion site reaction   

Investigations   G3/4 Blood bilirubin 

increased (< 2.5%); 

G3/4 Blood alkaline 

phosphatase increased 

(< 2.5%) 

G3/4 AST increased 

(< 1%); 

G3/4 ALT increased 

(< 1%) 

 

Tabulated list of adverse reactions in non-small cell lung cancer for DOCETAXEL KABI 75 mg/m² in 

combination with cisplatin 

 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 5.7%)     

Blood and 

lymphatic system 

disorders 

Neutropenia (G4: 51.5%); 

Anaemia (G3/4: 6.9%); 

Thrombocytopenia 

(G4: 0.5%) 

Febrile neutropenia   

Immune system 

disorders 

Hypersensitivity 

(G3/4: 2.5%) 

    

Metabolism and 

nutrition disorders 

Anorexia     

Nervous system 

disorders 

Peripheral sensory 

neuropathy (G3: 3.7%); 

Peripheral motor 

neuropathy (G3/4: 2%) 

    

Cardiac disorders   Arrhythmia 

(G3/4: 0.7%) 

Cardiac failure 

Vascular disorders   Hypotension 

(G3/4: 0.7%) 

  

Gastrointestinal 

disorders 

Nausea (G3/4: 9.6%); 

Vomiting (G3/4: 7.6%); 

Diarrhoea (G3/4: 6.4%); 

Stomatitis (G3/4: 2%) 

Constipation   

Skin and 

subcutaneous 

tissue disorders 

Alopecia; 

Nail disorders 

(severe: 0.7%); 

Skin reaction (G3/4: 0.2%) 

    

Musculoskeletal 

and connective 

Myalgia (severe: 0.5%)     



108 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

tissue disorders 

General disorders 

and administration 

site conditions 

Asthenia (severe: 9.9%); 

Fluid retention 

(severe: 0.7%); 

Fever (G3/4: 1.2%) 

Infusion site reaction; 

Pain 

  

Investigations   G3/4 Blood bilirubin 

increased (2.1%); G3/4 

ALT increased (1.3%) 

G3/4 AST increased 

(0.5%); G3/4 Blood 

alkaline phosphatase 

increased (0.3%) 

 

Tabulated list of adverse reactions in breast cancer for DOCETAXEL KABI 100 mg/m² in 

combination with trastuzumab 

 

MedDRA system 

organ classes 

Very common adverse reactions Common adverse reactions 

 

Blood and lymphatic 

system disorders 

Neutropenia (G3/4: 32%); 

Febrile neutropenia (includes 

neutropenia associated with fever and 

antibiotic use) or neutropenic sepsis  

  

Metabolism and 

nutrition disorders 

Anorexia   

Psychiatric disorders Insomnia   

Nervous system 

disorders 

Paraesthesia; Headache; Dysgeusia; 

Hypoaesthesia 

  

Eye disorders Lacrimation increased; Conjunctivitis   

Cardiac disorders   Cardiac failure 

Vascular disorders Lymphoedema   

Respiratory, thoracic 

and mediastinal 

disorders 

Epistaxis; Pharyngolaryngeal pain; 

Nasopharyngitis; Dyspnoea; 

Cough; Rhinorrhoea 

  

Gastrointestinal 

disorders 

Nausea; Diarrhoea; Vomiting; 

Constipation; Stomatitis; Dyspepsia; 

Abdominal pain 

  

Skin and 

subcutaneous tissue 

disorders 

Alopecia; Erythema; Rash; Nail 

disorders 

  

Musculoskeletal and 

connective tissue 

disorders 

Myalgia; Arthralgia; Pain in 

extremity; Bone pain; Back pain 

  

General disorders 

and administration 

site conditions 

Asthenia; Oedema peripheral; 

Pyrexia; Fatigue; Mucosal 

inflammation; Pain; Influenza like 

illness; Chest pain; Chills 

Lethargy 

Investigations Weight increased   

 



109 

Description of selected adverse reactions in breast cancer for DOCETAXEL KABI 100 mg/m² in 

combination with trastuzumab 

 

Blood and lymphatic system disorders 

Very common: Haematological toxicity was increased in patients receiving trastuzumab and 

docetaxel, compared with docetaxel alone (32% grade 3/4 neutropenia versus 22%, using NCI-CTC 

criteria). Note that this is likely to be an underestimate since docetaxel alone at a dose of 100 mg/m2 is 

known to result in neutropenia in 97% of patients, 76% grade 4, based on nadir blood counts. The 

incidence of febrile neutropenia/neutropenic sepsis was also increased in patients treated with 

Herceptin plus docetaxel (23% versus 17% for patients treated with docetaxel alone). 

 

Cardiac disorders 

Symptomatic cardiac failure was reported in 2.2% of the patients who received docetaxel plus 

trastuzumab compared to 0% of patients given docetaxel alone. In the docetaxel plus trastuzumab arm, 

64% had received a prior anthracycline as adjuvant therapy compared with 55% in the docetaxel arm 

alone. 

 

Tabulated list of adverse reactions in breast cancer for DOCETAXEL KABI 75 mg/m² in combination 

with capecitabine 

 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Infections and infestations   Oral candidiasis (G3/4: < 1%) 

Blood and lymphatic system 

disorders 

Neutropenia (G3/4: 63%); 

Anaemia (G3/4: 10%) 

Thrombocytopenia (G3/4: 3%) 

Metabolism and nutrition 

disorders 

Anorexia (G3/4: 1%); 

Decreased appetite 

Dehydration (G3/4: 2%) 

Nervous system disorders Dysgeusia (G3/4: < 1%); 

Paraesthesia (G3/4: < 1%) 

 

Dizziness; 

Headache (G3/4: < 1%); 

Neuropathy peripheral 

Eye disorders Lacrimation increased   

Respiratory, thoracic and 

mediastinal disorders 

Pharyngolaryngeal pain 

(G3/4: 2%) 

Dyspnoea (G3/4: 1%); 

Cough (G3/4: < 1%); 

Epistaxis (G3/4: < 1%) 

Gastrointestinal disorders Stomatitis (G3/4: 18%); 

Diarrhoea (G3/4: 14%); 

Nausea (G3/4: 6%); 

Vomiting (G3/4: 4%); 

Constipation (G3/4: 1%); 

Abdominal pain (G3/4: 2%); 

Dyspepsia 

Abdominal pain upper; 

Dry mouth 

Skin and subcutaneous tissue 

disorders 

Hand-foot syndrome 

(G3/4: 24%); 

Alopecia (G3/4: 6%); 

Nail disorders (G3/4: 2%) 

Dermatitis; 

Rash erythematous 

(G3/4: < 1%); 

Nail discolouration; 

Onycholysis (G3/4: 1%) 

Musculoskeletal and 

connective tissue disorders 

Myalgia (G3/4: 2%); 

Arthralgia (G3/4: 1%) 

Pain in extremity (G3/4: < 1%); 

Back pain (G3/4: 1%) 

General disorders and 

administration site conditions 

Asthenia (G3/4: 3%); 

Pyrexia (G3/4: 1%); 

Fatigue/weakness (G3/4: 5%); 

Lethargy; 

Pain 



110 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Oedema peripheral (G3/4: 1%) 

Investigations   Weight decreased; 

G3/4 Blood bilirubin increased 

(9%) 

 

Tabulated list of adverse reactions in metastatic castration-resistant prostate cancer for DOCETAXEL 

KABI 75 mg/m² in combination with prednisone or prednisolone 

 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Infections and infestations Infection (G3/4: 3.3%)   

Blood and lymphatic system 

disorders 

Neutropenia (G3/4: 32%); 

Anaemia (G3/4: 4.9%) 

Thrombocytopenia 

(G3/4: 0.6%); 

Febrile neutropenia 

Immune system disorders   Hypersensitivity (G3/4: 0.6%) 

Metabolism and nutrition 

disorders 

Anorexia (G3/4: 0.6%)   

Nervous system disorders Peripheral sensory neuropathy 

(G3/4: 1.2%); 

Dysgeusia (G3/4: 0%) 

Peripheral motor neuropathy 

(G3/4: 0%) 

Eye disorders   Lacrimation increased 

(G3/4: 0.6%) 

Cardiac disorders   Cardiac left ventricular 

function decrease (G3/4: 0.3%) 

Respiratory, thoracic and 

mediastinal disorders 

  Epistaxis (G3/4: 0%); 

Dyspnoea (G3/4: 0.6%); 

Cough (G3/4: 0%) 

Gastrointestinal disorders Nausea (G3/4: 2.4%); 

Diarrhoea (G3/4: 1.2%); 

Stomatitis/Pharyngitis 

(G3/4: 0.9%); 

Vomiting (G3/4: 1.2%) 

  

Skin and subcutaneous tissue 

disorders 

Alopecia; 

Nail disorders (no severe) 

Exfoliative rash (G3/4: 0.3%) 

Musculoskeletal and 

connective bone disorders 

  Arthralgia (G3/4: 0.3%); 

Myalgia (G3/4: 0.3%) 

General disorders and 

administration site conditions 

Fatigue (G3/4: 3.9%); 

Fluid retention (severe: 0.6%) 

  

 



111 

Tabulated list of adverse reactions in high-risk locally advanced or metastatic hormone-sensitive 

prostate cancer for DOCETAXEL KABI 75 mg/m² in combination with prednisone or prednisolone 

and ADT (STAMPEDE study)  

 

MedDRA system organ 

classes 

 

Very common adverse 

reactions 

Common adverse reactions 

Blood and lymphatic system 

disorders 

Neutropenia (G3-4: 12 %) 

Anaemia  

Febrile neutropenia (G3-4: 15%) 

 

Immune system disorders   Hypersensitivity (G3-4: 1%) 

Endocrine disorders  Diabetes (G3-4: 1%) 

Metabolism and nutrition 

disorders 

 Anorexia  

Psychiatric disorders Insomnia (G3: 1%)  

Nervous system disorders Peripheral sensory neuropathy 

(≥G3: 2%)a 

Headache 

 

Dizziness 

Eye disorders  Blurred vision 

Cardiac disorders  Hypotension (G3: 0%) 

 

Respiratory, thoracic and 

mediastinal disorders  

Dyspnea (G3: 1%) 

Coughing (G3: 0%) 

Upper respiratory tract infection 

(G3: 1%)  

Pharyngitis (G3: 0%) 

 

 

Gastrointestinal disorders  Diarrhea (G3: 3%) 

Stomatitis (G3: 0%) 

Constipation (G3: 0%) 

Nausea (G3: 1%) 

Dyspepsia 

Abdominal pain (G3: 0%) 

Flatulence 

Vomiting (G3: 1%) 

 

Skin and subcutaneous tissue 

disorders 

Alopecia (G3: 3%)a 

Nail changes (G3: 1%) 

Rash 

Musculoskeletal and 

connective tissue disorders 

Myalgia   

General disorders and 

administration site conditions 

Lethargy (G3-4: 2%) 

Flu-like symptoms (G3: 0%) 

Asthenia (G3: 0%) 

Fluid retention 

Fever (G3: 1%) 

Oral candidiasis  

Hypocalcaemia (G3: 0%) 

Hypophosphataemia (G3-4: 1%) 

Hypokalaemia (G3: 0%) 
a From the GETUG AFU15 study 
 

Tabulated list of adverse reactions in breast cancer for adjuvant therapy with DOCETAXEL KABI 

75 mg/m² in combination with doxorubicin and cyclophosphamide in patients with node-positive 

(TAX 316) and node-negative (GEICAM 9805) breast cancer - pooled data 

 



112 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 2.4%); 

Neutropenic infection 

(G3/4: 2.6%) 

    

Blood and 

lymphatic system 

disorders 

Anaemia (G3/4: 3%); 

Neutropenia 

(G3/4: 59.2%); 

Thrombocytopenia 

(G3/4: 1.6%); 

Febrile neutropenia 

(G3/4: NA) 

    

Immune system 

disorders 

  Hypersensitivity 

(G3/4: 0.6 %) 

  

Metabolism and 

nutrition disorders 

Anorexia (G3/4: 1.5%)     

Nervous system 

disorders 

Dysgeusia (G3/4: 0.6%); 

Peripheral sensory 

neuropathy 

(G3/4: < 0.1%) 

Peripheral motor 

neuropathy 

(G3/4: 0%) 

Syncope (G3/4: 0%); 

Neurotoxicity 

(G3/4: 0%); 

Somnolence (G3/4: 0%) 

Eye disorders  Conjunctivitis 

(G3/4: < 0.1%) 

Lacrimation 

increased 

(G3/4:  < 0.1%) 

  

Cardiac disorders   Arrhythmia 

(G3/4: 0.2%) 

  

Vascular disorders Hot flush (G3/4: 0.5%) Hypotension 

(G3/4: 0%); 

Phlebitis 

(G3/4: 0%) 

Lymphoedema 

(G3/4: 0%) 

Respiratory, 

thoracic and 

mediastinal 

disorders 

  Cough (G3/4: 0%)   

Gastrointestinal 

disorders 

Nausea (G3/4: 5.0%); 

Stomatitis (G3/4: 6.0%); 

Vomiting (G3/4: 4.2%); 

Diarrhoea (G3/4: 3.4%); 

Constipation 

(G3/4: 0.5%) 

Abdominal pain 

(G3/4: 0.4%) 

 

Skin and 

subcutaneous tissue 

disorders 

Alopecia 

( persisting: < 3%); 

Skin disorder  

(G3/4: 0.6%); 

Nail disorders 

(G3/4: 0.4%) 

    

Musculoskeletal 

and connective 

tissue disorders 

Myalgia (G3/4: 0.7%); 

Arthralgia (G3/4: 0.2%) 

    

Reproductive Amenorrhoea      



113 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

system and breast 

disorders 

(G3/4: NA) 

General disorders 

and administration 

site conditions 

Asthenia  

(G3/4: 10.0%); 

Pyrexia (G3/4: NA); 

Oedema peripheral 

(G3/4: 0.2%) 

    

Investigations   Weight increased 

(G3/4: 0%); 

Weight decreased 

(G3/4: 0.2%) 

  

 

Description of selected adverse reactions for adjuvant therapy with DOCETAXEL KABI 75 mg/m² in 

combination with doxorubicin and cyclophosphamide in patients with node-positive (TAX 

316) and node-negative (GEICAM 9805) breast cancer 

 

Nervous system disorders 

In study TAX316 peripheral sensory neuropathy started during the treatment period and persisted into 

the follow-up period in 84 patients (11.3%) in TAC arm and 15 patients (2 %) in FAC arm. At the end 

of the follow-up period (median follow-up time of 8 years), peripheral sensory neuropathy was 

observed to be ongoing in 10 patients (1.3%) in TAC arm, and in 2 patients (0.3%) in FAC arm. 

In GEICAM 9805 study peripheral sensory neuropathy that started during the treatment period 

persisted into the follow-up period in 10 patients (1.9%) in TAC arm and 4 patients (0.8 %) in FAC 

arm. At the end of the follow-up period (median follow-up time of 10 years and 5 months), peripheral 

sensory neuropathy was observed to be ongoing in 3 patients (0.6%) in TAC arm, and in 1 patient 

(0.2%) in FAC arm. 

 

Cardiac disorders 

In study TAX316, 26 patients (3.5%) in the TAC arm and 17 patients (2.3%) in the FAC arm 

experienced congestive heart failure. All except one patient in each arm were diagnosed with CHF 

more than 30 days after the treatment period. Two patients in the TAC arm and 4 patients in the FAC 

arm died because of cardiac failure. 

In GEICAM 9805 study, 3 patients (0.6 %) in TAC arm and 3 patients (0.6 %) in FAC arm developed 

congestive heart failure during the follow-up period.  At the end of the follow-up period (actual 

median follow-up time of 10 years and 5 months), no patients  had CHF in TAC arm and 1 patient in 

TAC arm died because of dilated cardiomyopathy, and CHF was observed to be ongoing in 1 patient 

(0.2%) in FAC arm. 

 

Skin and subcutaneous tissue disorders 

In study TAX316  alopecia persisting into the follow-up period after the end of chemotherapy was 

reported in 687 of 744 TAC patients (92.3%) and 645 of 736FAC patients(87.6%).. 

At the end of the follow-up period actual median follow-up time of 8 years), alopecia was observed to 

be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%). 

 

In GEICAM 9805 study alopecia that started during the treatment period and persisted into the follow-

up was observed to be ongoing in 49 patients (9.2 %) in TAC arm and 35 patients (6.7 %) in FAC arm. 

Alopecia related to study drug started or worsened during the follow-up period in 42 patients (7.9 %) 

in TAC arm and 30 patients (5.8 %) in FAC arm. At the end of the follow-up period (median follow-

up time of 10 years and 5 months), alopecia was observed to be ongoing in 3 patients (0.6%) in TAC 

arm, and in 1 patient (0.2%) in FAC arm.   

 

 

 



114 

Reproductive system and breast disorders 

In TAX316 amenorrhoea that started during the treatment period and persisted into the follow-up 

period after the end of chemotherapy was reported in 202 of 744 TAC patients (27.2%) and 125 of 736 

FAC patients (17.0%). Amenorrhea was observed to be ongoing at the end of the follow-up period 

(median follow-up time of 8 years) in 121 of 744 TAC patients (16.3%) and 86 FAC patients (11.7%). 

In GEICAM 9805 study amenorrhoea that started during the treatment period and persisted into the 

follow-up period was observed to be ongoing in 18 patients (3.4 %) in TAC arm and 5 patients (1.0 %) 

in FAC arm. At the end of the follow-up period (median follow-up time of 10 years and 5 months), 

amenorrhoea was observed to be ongoing in 7 patients (1.3%) in TAC arm, and in 4 patients (0.8%) in 

FAC arm. 

 

General disorders and administration site conditions 

In study TAX316 peripheral oedema that started during the treatment period and persisted into the 

follow-up period after the end of chemotherapy was observed in 119 of 744 TAC patients (16.0%) and 

23 of 736 FAC patients (3.1%). At the end of the follow-up period (actual median follow-up time of 8 

years), peripheral oedema was ongoing in19 TAC patients (2.6%) and 4 FAC patients (0.5%).  

In study TAX316 lymphoedema that started during the treatment period and persisted into the follow-

up period after the end of chemotherapy was reported in 11 of 744 TAC patients (1.5%) and 1 of 736 

FAC patients (0.1%). At the end of the follow-up period (actual median follow-up time of 8 years), 

lymphoedema was observed to be ongoing in 6 TAC patients (0.8%) and 1 FAC patient (0.1%). 

In study TAX316 asthenia that started during the treatment period and persisted into the follow-up 

period after the end of chemotherapy was reported in 236 of 744 TAC patients (31.7%) and 180 of 736 

FAC patients (24.5%). At the end of the follow-up period (actual median follow-up time of 8 years), 

asthenia was observed to be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%). 

 

In study GEICAM 9805 peripheral oedema that started during the treatment period persisted into the 

follow-up period in 4 patients (0.8%) in TAC arm and in 2 patients (0.4%) in FAC arm. At the end of 

the follow-up period (median follow-up time of 10 years and 5 months), no patients (0%) in TAC arm 

had peripheral oedema and it was observed to be ongoing in 1 patient (0.2%) in FAC arm. 

Lymphoedema that started during the treatment period persisted into the follow-up period in 5 patients 

(0.9%) in TAC arm and 2 patients (0.4 %) in FAC arm. At the end of the follow-up period, 

lymphoedema was observed to be ongoing in 4 patients (0.8%) in TAC arm, and in 1 patient (0.2%) in 

FAC arm.  

Asthenia that started during the treatment period and persisted into the follow-up period was observed 

to be ongoing in 12 patients (2.3 %) in TAC arm and 4 patients (0.8 %) in FAC arm. At the end of the 

follow-up period, asthenia was observed to be ongoing in 2 patients (0.4%) in TAC arm, and in 2 

patients (0.4%) in FAC arm. 

 

Acute leukaemia / Myelodysplastic syndrome 

After 10 years of follow up in study TAX316, acute leukaemia was reported in 3 of 744 TAC patients 

(0.4%) and in 1 of 736 FAC patients (0.1%). One TAC patient (0.1%) and 1 FAC patient (0.1%) died 
due to AML during the follow-up period (median follow-up time of 8 years).  Myelodysplastic 

syndrome was reported in 2 of 744 TAC patients (0.3%) and in 1 of 736 FAC patients (0.1%). 

After 10 years of follow-up in GEICAM 9805 study, acute leukaemia occurred in 1 of 532 (0.2%) 

patients in TAC arm. No cases were reported in patients in FAC. No patient was diagnosed with 

myelodysplastic syndrome in either treatment groups. 

 

Neutropenic complications 

Table below shows that the incidence of Grade 4 neutropenia, febrile neutropenia and neutropenic 

infection was decreased in patients who received primary G-CSF prophylaxis after it was made 

mandatory in the TAC arm – GEICAM study. 

 

 

 

 

 

 



115 

Neutropenic complications in patients receiving TAC with or without primary G-CSF prophylaxis 

(GEICAM 9805) 

 

 Without primary 

G-CSF prophylaxis 

(n = 111) 

n (%) 

With primary 

G-CSF prophylaxis 

(n = 421) 

n (%) 

Neutropenia (Grade 4) 104 (93.7) 135 (32.1) 

Febrile neutropenia 28 (25.2) 23 (5.5) 

Neutropenic infection 14 (12.6) 21 (5.0) 

Neutropenic infection 

(Grade 3-4) 

2 (1.8) 5 (1.2) 

 

Tabulated list of adverse reactions in gastric adenocarcinoma center for DOCETAXEL KABI 

75 mg/m² in combination with cisplatin and 5-fluorouracil 

 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse reactions 

Infections and 

infestations 

Neutropenic infection; 

Infection (G3/4: 11.7%) 

  

Blood and lymphatic 

system disorders 

Anaemia (G3/4: 20.9%); 

Neutropenia (G3/4: 83.2%); 

Thrombocytopenia (G3/4: 8.8%); 

Febrile neutropenia  

  

Immune system 

disorders 

Hypersensitivity (G3/4: 1.7%)   

Metabolism and 

nutrition disorders 

Anorexia (G3/4: 11.7%)   

Nervous system 

disorders 

Peripheral sensory neuropathy 

(G3/4: 8.7%) 

Dizziness (G3/4: 2.3%); 

Peripheral motor neuropathy 

(G3/4: 1.3%) 

Eye disorders   Lacrimation increased (G3/4: 0%) 

Ear and labyrinth 

disorders 

  Hearing impaired (G3/4: 0%) 

Cardiac disorders   Arrhythmia (G3/4: 1.0%) 

Gastrointestinal 

disorders 

Diarrhoea (G3/4: 19.7%); 

Nausea (G3/4: 16%); 

Stomatitis (G3/4: 23.7%); 

Vomiting (G3/4: 14.3%) 

Constipation (G3/4: 1.0%); 

Gastrointestinal pain (G3/4: 1.0%); 

Oesophagitis/dysphagia/ 

odynophagia (G3/4: 0.7%) 

Skin and subcutaneous 

tissue disorders 

Alopecia (G3/4: 4.0%) Rash pruritus (G3/4: 0.7%); 

Nail disorders (G3/4: 0.7%); 

Skin exfoliation (G3/4: 0%) 

General disorders and 

administration site 

conditions 

Lethargy (G3/4: 19.0%); 

Fever (G3/4: 2.3%); 

Fluid retention (severe/life-

threatening: 1%) 

  

 

Description of selected adverse reactions in gastric adenocarcinoma cancer for DOCETAXEL KABI 

75 mg/m2 in combination with cisplatin and 5-fluorouracil 

 



116 

Blood and lymphatic system disorders 

Febrile neutropenia and neutropenic infection occurred in 17.2% and 13.5% of patients respectively, 

regardless of G-CSF use. G-CSF was used for secondary prophylaxis in 19.3% of patients (10.7% of 

the cycles). Febrile neutropenia and neutropenic infection occurred respectively in 12.1% and 3.4% of 

patients when patients received prophylactic G-CSF, in 15.6% and 12.9% of patients without 

prophylactic G-CSF (see section 4.2). 

 

Tabulated list of adverse reactions in head and neck cancer for DOCETAXEL KABI 75 mg/m² in 

combination with cisplatin and 5-fluorouracil  

 

• Induction chemotherapy followed by radiotherapy (TAX 323)  
 

MedDRA system 

organ classes 

Very common adverse 

reactions 

 

Common adverse 

reactions 

 

Uncommon 

adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 6.3%); 

Neutropenic infection 

    

Neoplasms benign, 

malignant and 

unspecified (incl 

cysts and polyps) 

  Cancer pain (G3/4: 0.6%)   

Blood and lymphatic 

system disorders 

Neutropenia 

(G3/4: 76.3%); 

Anaemia (G3/4: 9.2%); 

Thrombocytopenia 

(G3/4: 5.2%) 

Febrile neutropenia   

Immune system 

disorders 

  Hypersensitivity (no 

severe) 

  

Metabolism and 

nutrition disorders 

Anorexia (G3/4: 0.6%)     

Nervous system 

disorders 

Dysgeusia/Parosmia; 

Peripheral sensory 

neuropathy (G3/4: 0.6%) 

Dizziness   

Eye disorders   Lacrimation increased; 

Conjunctivitis  

  

Ear and labyrinth 

disorders 

  Hearing impaired   

Cardiac disorders   Myocardial ischemia 

(G3/4: 1.7%) 

Arrhythmia 

(G3/4: 0.6%) 

Vascular disorders   Venous disorder 

(G3/4: 0.6%) 

  

Gastrointestinal 

disorders 

Nausea (G3/4: 0.6%); 

Stomatitis (G3/4: 4.0%); 

Diarrhoea (G3/4: 2.9%); 

Vomiting (G3/4: 0.6%) 

Constipation; 

Esophagitis/dysphagia/ 

odynophagia 

(G3/4: 0.6%); 

Abdominal pain; 

Dyspepsia; 

Gastrointestinal 

haemorrhage 

(G3/4: 0.6%)  

  



117 

MedDRA system 

organ classes 

Very common adverse 

reactions 

 

Common adverse 

reactions 

 

Uncommon 

adverse 

reactions 

Skin and 

subcutaneous tissue 

disorders 

Alopecia (G3/4: 10.9%) Rash pruritic; 

Dry skin; 

Skin exfoliative 

(G3/4: 0.6%) 

  

Musculoskeletal and 

connective tissue 

disorders 

  Myalgia (G3/4: 0.6%)   

General disorders and 

administration site 

conditions 

Lethargy (G3/4: 3.4%); 

Pyrexia (G3/4: 0.6%); 

Fluid retention; 

Oedema 

    

Investigations   Weight increased   

 

• Induction chemotherapy followed by chemoradiotherapy (TAX 324)  
 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 3.6%) 

  

Neutropenic 

infection 

  

Neoplasms benign, 

malignant and 

unspecified (incl 

cysts and polyps) 

  Cancer pain 

(G3/4: 1.2%) 

  

Blood and lymphatic 

system disorders 

Neutropenia 

(G3/4: 83.5%); 

Anaemia (G3/4: 12.4%); 

Thrombocytopenia 

(G3/4: 4.0%); 

Febrile neutropenia 

    

Immune system 

disorders 

    Hypersensitivity 

Metabolism and 

nutrition disorders 

Anorexia (G3/4: 12.0%)     

Nervous system 

disorders 

Dysgeusia/Parosmia 

(G3/4: 0.4%); 

Peripheral sensory 

neuropathy (G3/4: 1.2%) 

Dizziness 

(G3/4: 2.0%); 

Peripheral motor 

neuropathy 

(G3/4: 0.4%) 

  

Eye disorders   Lacrimation 

increased 

Conjunctivitis 

Ear and labyrinth 

disorders 

Hearing impaired 

(G3/4: 1.2%) 

    

Cardiac disorders   Arrhythmia 

(G3/4: 2.0%) 

Ischemia myocardial 

Vascular disorders     Venous disorder 



118 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Gastrointestinal 

disorders 

Nausea (G3/4: 13.9%); 

Stomatitis (G3/4: 20.7%); 

Vomiting (G3/4: 8.4%); 

Diarrhoea (G3/4: 6.8%); 

Esophagitis/dysphagia/ 

odynophagia 

(G3/4: 12.0%); 

Constipation (G3/4: 0.4%) 

Dyspepsia 

(G3/4: 0.8%); 

Gastrointestinal pain 

(G3/4: 1.2%); 

Gastrointestinal 

haemorrhage 

(G3/4: 0.4%) 

  

Skin and 

subcutaneous tissue 

disorders 

Alopecia (G3/4: 4.0%); 

Rash pruritic 

Dry skin; 

Desquamation 

  

Musculoskeletal, 

connective tissue 

bone disorders 

  Myalgia 

(G3/4: 0.4%) 

  

General disorders and 

administration site 

conditions 

Lethargy (G3/4: 4.0%); 

Pyrexia (G3/4: 3.6%); 

Fluid retention (G3/4: 1.2); 

Oedema (G3/4: 1.2%) 

    

Investigations Weight decreased   Weight increased 

 

Post-marketing experience 

 

Neoplasms benign, malignant and unspecified (incl cysts and polyps) 

Second primary malignancies (frequency not known), including non-Hodgkin lymphoma have been 

reported in association with docetaxel when used in combination with other anticancer treatments 

known to be associated with second primary malignancies. Acute myeloid leukemia and 

myelodysplastic syndrome have been reported (frequency uncommon) in pivotal clinical studies in 

breast cancer with TAC regimen. 

 

Blood and lymphatic system disorders 

Bone marrow suppression and other haematologic adverse reactions have been reported. Disseminated 

intravascular coagulation (DIC), often in association with sepsis or multi-organ failure, has been 

reported. 

 

Immune system disorders 

Some cases of anaphylactic shock, sometimes fatal, have been reported. 

Hypersensitivity reactions (frequency not known) have been reported with docetaxel in patients who 

previously experienced hypersensitivity reactions to paclitaxel. 

 

Nervous system disorders 

Rare cases of convulsion or transient loss of consciousness have been observed with docetaxel 

administration. These reactions sometimes appear during the infusion of the medicinal product. 

 

Eye disorders 

Very rare cases of transient visual disturbances (flashes, flashing lights, scotomata) typically occurring 

during infusion of the medicinal product and in association with hypersensitivity reactions have been 

reported. These were reversible upon discontinuation of the infusion. Cases of lacrimation with or 

without conjunctivitis, as cases of lacrimal duct obstruction resulting in excessive tearing have been 

rarely reported. Cases of cystoid macular oedema (CMO) have been reported in patients treated with 

docetaxel. 

 

 



119 

Ear and labyrinth disorders 

Rare cases of ototoxicity, hearing impaired and/or hearing loss have been reported. 

 

Cardiac disorders 

Rare cases of myocardial infarction have been reported. 

Ventricular arrhythmia including ventricular tachycardia (frequency not known), sometimes fatal, has 

been reported in patients treated with docetaxel in combination regimens including doxorubicin, 5-

fluorouracil and/ or cyclophosphamide. 

 

Vascular disorders 

Venous thromboembolic events have rarely been reported. 

 

Respiratory, thoracic and mediastinal disorders 

Acute respiratory distress syndrome and cases of interstitial pneumonia/ pneumonitis, interstitial lung 
disease, pulmonary fibrosis and respiratory failure sometimes fatal have rarely been reported. Rare 

cases of radiation pneumonitis have been reported in patients receiving concomitant radiotherapy. 

 

Gastrointestinal disorders 

Rare cases of enterocolitis, including colitis, ischemic colitis, and neutropenic enterocolitis, have been 

reported with a potential fatal outcome (frequency not known). 

Rare occurrences of dehydration have been reported as a consequence of gastrointestinal events 

including enterocolitis and gastrointestinal perforation.  

Rare cases of ileus and intestinal obstruction have been reported. 

 

Hepatobiliary disorders 

Very rare cases of hepatitis, sometimes fatal primarily in patients with pre-existing liver disorders, 

have been reported. 

 

Skin and subcutaneous tissue disorders 

Cases of cutaneous lupus erythematosus, bullous eruptions such as erythema multiforme and severe 

cutaneous adverse reactions such as Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis 

(TEN) and Acute Generalized Exanthematous Pustulosis (AGEP) have been reported with docetaxel.  

Scleroderma-like changes usually preceded by peripheral lymphoedema have been reported with 

docetaxel. Cases of permanent alopecia (frequency not known) have been reported. 

 

Renal and urinary disorders 

Renal insufficiency and renal failure have been reported. In about 20% of these cases there were no 

risk factors for acute renal failure such as concomitant nephrotoxic medicinal products and 

gastrointestinal disorders. 

 

General disorders and administration site conditions 

Radiation recall phenomena have rarely been reported. 

Injection site recall reaction (recurrence of skin reaction at a site of previous extravasation following 

administration of docetaxel at a different site) has been observed at the site of previous extravasation 

(frequency not known). 

Fluid retention has not been accompanied by acute episodes of oliguria or hypotension. Dehydration 

and pulmonary oedema have rarely been reported. 

Metabolism and nutrition disorders 

Cases of electrolyte imbalance have been reported. Cases of hyponatraemia have been reported, 

mostly associated with dehydration, vomiting and pneumonia. Hypokalaemia, hypomagnesaemia, and 

hypocalcaemia were observed, usually in association with gastrointestinal disorders and in particular 

with diarrhoea. 

 

Reporting of suspected adverse reactions 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 



120 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

 

4.9 Overdose 

 

There were a few reports of overdose. There is no known antidote for docetaxel overdose. In case of 

overdose, the patient should be kept in a specialised unit and vital functions closely monitored. In 

cases of overdose, exacerbation of adverse events may be expected. The primary anticipated 

complications of overdose would consist of bone marrow suppression, peripheral neurotoxicity and 

mucositis. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. 

Other appropriate symptomatic measures should be taken, as needed. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: antineoplastic agents, plant alkaloids and other natural products, taxanes, 

ATC Code: L01CD02  

 

Mechanism of action 

 

Docetaxel is an antineoplastic agent which acts by promoting the assembly of tubulin into stable 

microtubules and inhibits their disassembly which leads to a marked decrease of free tubulin. The 

binding of docetaxel to microtubules does not alter the number of protofilaments. 

 

Docetaxel has been shown in vitro to disrupt the microtubular network in cells which is essential for 

vital mitotic and interphase cellular functions. 

 

Pharmacodynamic effects 

 

Docetaxel was found to be cytotoxic in vitro against various murine and human tumour cell lines and 

against freshly excised human tumour cells in clonogenic assays. Docetaxel achieves high intracellular 

concentrations with a long cell residence time. In addition, docetaxel was found to be active on some 

but not all cell lines over expressing the p-glycoprotein which is encoded by the multidrug resistance 

gene. In vivo, docetaxel is schedule independent and has a broad spectrum of experimental anti-tumour 

activity against advanced murine and human grafted tumours. 

 

Clinical efficacy and safety 

 

Breast cancer 

 

DOCETAXEL KABI in combination with doxorubicin and cyclophosphamide: adjuvant therapy 

 

Patients with operable node-positive breast cancer (TAX 316) 

 

Data from a multi-centre open-label randomised study support the use of docetaxel for the adjuvant 
treatment of patients with operable node-positive breast cancer and KPS ≥ 80%, between 18 and 

70 years of age. After stratification according to the number of positive lymph nodes (1-3, 

4+), 1491 patients were randomised to receive either docetaxel 75 mg/m2 administered 1-hour after 

doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (TAC arm), or doxorubicin 50 mg/m2 

followed by fluorouracil 500 mg/m2 and cyclosphosphamide 500 mg/m2 (FAC arm). Both regimens 

were administered once every 3 weeks for 6 cycles. Docetaxel was administered as a 1-hour infusion, 

all other medicinal products were given as intravenous bolus on day one. G-CSF was administered as 

secondary prophylaxis to patients who experienced complicated neutropenia (febrile neutropenia, 

prolonged neutropenia, or infection). Patients on the TAC arm received antibiotic prophylaxis with 



121 

ciprofloxacin 500 mg orally twice daily for 10 days starting on day 5 of each cycle, or equivalent. In 

both arms, after the last cycle of chemotherapy, patients with positive oestrogen and/or progesterone 

receptors received tamoxifen 20 mg daily for up to 5 years. Adjuvant radiation therapy was prescribed 

according to guidelines in place at participating institutions and was given to 69% of patients who 

received TAC and 72% of patients who received FAC. Two interim analyses and one final analysis 

were performed. The first interim analysis was planned 3 years after the date when half of study 

enrolment was done. The second interim analysis was done after 400 DFS events had been recorded 

overall, which led to a median follow-up of 55 months. The final analysis was performed when all 

patients had reached their 10-year follow-up visit (unless they had a DFS event or were lost to follow 

up before). Disease-free survival (DFS) was the primary efficacy endpoint and Overall survival (OS) 

was the secondary efficacy endpoint. 

 

A final analysis was performed with an actual median follow up of 96 months. Significantly longer 

disease-free survival for the TAC arm compared to the FAC arm was demonstrated. Incidence of 

relapses at 10 years was reduced in patients receiving TAC compared to those who received FAC 

(39% versus 45%, respectively) i.e. an absolute risk reduction by 6% (p = 0.0043). Overall survival at 

10 years was also significantly increased with TAC compared to FAC (76% versus 69%, respectively) 

i.e. an absolute reduction of the risk of death by 7% (p = 0.002). As the benefit observed in patients 

with 4+ nodes was not statistically significant on DFS and OS, the positive benefit/risk ratio for TAC 

in patients with 4+ nodes was not fully demonstrated at the final analysis. 

 

Overall, the study results demonstrate a positive benefit risk ratio for TAC compared to FAC. 

 

TAC-treated patient subsets according to prospectively defined major prognostic factors were 

analysed:  

 

  Disease free survival Overall Survival 

Patient 

subset 

Number 

of patients 

Hazard 

ratio* 

95% CI p = Hazard 

ratio* 

95% CI p = 

No of 

positive 

nodes 

Overall 

1-3 

4+ 

 

 

 

745 

467 

278 

 

 

 

0.80 

0.72 

0.87 

 

 

 

0.68-0.93 

0.58-0.91 

0.70-1.09 

 

 

 

0.0043 

0.0047 

0.2290 

 

 

 

0.74 

0.62 

0.87 

 

 

 

0.61-0.90 

0.46-0.82 

0.67-1.12 

 

 

 

0.0020 

0.0008 

0.2746 

*a hazard ratio of less than 1 indicates that TAC is associated with a longer disease-free survival and 

overall survival compared to FAC  

 

Patients with operable node-negative breast cancer eligible to receive chemotherapy (GEICAM 9805) 

 

Data from a multi-centre open-label randomised trial support the use of DOCETAXEL KABI for the 

adjuvant treatment of patients with operable node-negative breast cancer eligible to receive 

chemotherapy. 1060 patients were randomised to receive either DOCETAXEL KABI 75 mg/m2 

administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (539 patients in 

TAC arm), or doxorubicin 50 mg/m2 followed by fluorouracil 500 mg/m2 and cyclosphosphamide 

500 mg/m2 (521 patients in FAC arm), as adjuvant treatment of operable node-negative breast cancer 

patients with high risk of relapse according to 1998 St. Gallen criteria (tumour size > 2 cm and/or 

negative ER and PR and/or high histological/nuclear grade (grade 2 to 3) and /or age < 35 years).). 

Both regimens were administered once every 3 weeks for 6 cycles. DOCETAXEL KABI was 

administered as a 1-hour infusion, all other medicinal product were given intraveinously on day 1 

every three weeks. Primary prophylactic G-CSF was made mandatory in TAC arm after 230 patients 

were randomised. The incidence of Grade 4 neutropenia, febrile neutropenia and neutropenic infection 

was decreased in patients who received primary G-CSF prophylaxis (see section 4.8). In both arms, 

after the last cycle of chemotherapy, patients with ER+ and/or PgR+ tumours received tamoxifen 

20 mg once a day for up to 5 years. Adjuvant radiation therapy was administered according to 



122 

guidelines in place at participating institutions and was given to 57.3% of patients who received TAC 

and 51.2% of patients who received FAC. 

 

One primary analysis and one updated analysis were performed. The primary analysis was done when 

all patients had a follow-up of greater than 5 years (median follow-up time of 77 months). The updated 

analysis was performed when all patients had reached their 10-year (median follow up time of 10 

years and 5 months) follow-up visit (unless they had a DFS event or were lost to follow-up 

previously). Disease-free survival (DFS) was the primary efficacy endpoint and Overall survival (OS) 

was the secondary efficacy endpoint. 

 

Athe median duration of follow-up  time of 77 months, significantly longer disease-free survival for 

the TAC arm compared to the FAC arm was demonstrated. TAC-treated patients had a 32% reduction 

in the risk of relapse compared to those treated with FAC (hazard ratio = 0.68, 95% CI (0.49-0.93), 

p = 0.01).  At the median follow up time of 10 years and 5 months, TAC-treated patients had a 16,5% 

reduction in the risk of relapse compared to those treated with FAC (hazard ratio = 0.84, 95% CI 

(0.65-1.08), p=0.1646). DFS data were not statistically significant but were still associated with a 

positive trend in favour of TAC. 

 

At the median follow-up time of 77 months, overall survival (OS) was longer in the TAC arm with 

TAC-treated patients having a 24% reduction in the risk of death compared to FAC (hazard ratio = 

0.76, 95% CI (0.46-1.26, p = 0.29). However, the distribution of OS was not significantly different 

between the 2 groups. 

At the median follow up time of 10 years and 5 months, TAC-treated patients had a 9% reduction in 

the risk of death compared to FAC-treated patients (hazard ratio = 0.91, 95% CI (0.63-1.32)).  

The survival rate was 93.7% in the TAC arm and 91.4 % in the FAC arm, at the 8-year follow-up time 

point, and 91.3 % in the TAC arm and 89 % in the FAC arm, at the 10-year follow-up time point. 

 

The positive benefit risk ratio for TAC compared to FAC remained unchanged. 

 

TAC-treated patient subsets according to prospectively defined major prognostic factors were analysed 

in the primary ana lysis (at the median follow-up time of 77 months) (see table below): 

 

Subset Analyses-Adjuvant Therapy in Patients with Node-negative Breast Cancer Study 

(Intent-to-Treat Analysis) 

 

Patient subset Number of patients 

in TAC group 

Disease Free Survival 

Hazard ratio* 95% CI 

Overall 539 0.68 0.49-0.93 

Age category 1 

<50 years  

≥50 years 

 

260 

279  

 

0.67 

0.67  

 

0.43-1.05 

0.43-1.05 

Age category 2 

<35 years 

≥35 years 

 

42 

497 

 

0.31 

0.73 

 

0.11-0.89 

0.52-1.01 

Hormonal receptor 

status 

Negative  

Positive 

 

 

195 

344 

 

 

0.7 

0.62 

 

 

0.45-1.1 

0.4-0.97 

Tumour size 

≤2 cm  

>2 cm 

 

285 

254 

 

0.69 

0.68 

 

0.43-1.1 

0.45-1.04 

Histological grade 

Grade1 (includes grade 

not assessed) 

Grade 2  

Grade 3 

 

64 

 

216 

259 

 

0.79 

 

0.77 

0.59 

 

0.24-2.6 

 

0.46-1.3 

0.39-0.9 

Menopausal status    



123 

Patient subset Number of patients 

in TAC group 

Disease Free Survival 

Hazard ratio* 95% CI 

Pre-Menopausal  

Post-Menopausal  

285 

254 

0.64 

0.72 

0.40-1 

0.47-1.12 

*a hazard ratio (TAC/FAC) of less than 1 indicates that TAC is associated with a longer disease free 

survival compared to FAC. 

 

Exploratory subgroup analyses for disease-free survival for patients who meet the 2009 St. Gallen 

chemotherapy criteria – (ITT population) were performed and presented here below 

 
 TAC 

 

FAC 

 

Hazard ratio 

(TAC/FAC) 

 

 

Subgroups (n=539) (n=521) (95% CI) p-value 

Meeting relative 

 indication 

for chemotherapya 

    

No 18/214 

(8.4%) 

26/227 

(11.5%) 

0.796 

(0.434 - 1.459) 

0.4593 

Yes 48/325 

(14.8%) 

69/294 

(23.5%) 

0.606 

(0.42 - 0.877) 

0.0072 

TAC = docetaxel, doxorubicin and cyclophosphamide 

FAC = 5-fluorouracil, doxorubicin and cyclophosphamide 

CI = confidence interval 

ER = oestrogen receptor 

PR = progesterone receptor 
a ER/PR-negative or Grade 3 or tumour size > 5 cm 

 

The estimated hazard ratio was using Cox proportional hazard model with treatment group as the 

factor. 

 

DOCETAXEL KABI as single agent 

 

Two randomised phase III comparative studies, involving a total of 326 alkylating or 

392 anthracycline failure metastatic breast cancer patients, have been performed with docetaxel at the 

recommended dose and regimen of 100 mg/m² every 3 weeks. 

 

In alkylating-failure patients, docetaxel was compared to doxorubicin (75 mg/m² every 3 weeks). 

Without affecting overall survival time (docetaxel 15 months vs. doxorubicin 14 months, p = 0.38) or 

time to progression (docetaxel 27 weeks vs. doxorubicin 23 weeks, p = 0.54), docetaxel increased 

response rate (52% vs. 37%, p = 0.01) and shortened time to response (12 weeks vs. 23 weeks, 

p= 0.007). Three docetaxel patients (2%) discontinued the treatment due to fluid retention, whereas 

15 doxorubicin patients (9%) discontinued due to cardiac toxicity (three cases of fatal congestive heart 

failure). 

 

In anthracycline-failure patients, docetaxel was compared to the combination of mitomycin C and 

vinblastine (12 mg/m² every 6 weeks and 6 mg/m² every 3 weeks). Docetaxel increased response rate 

(33% vs. 12%, p < 0.0001), prolonged time to progression (19 weeks vs. 11 weeks, p= 0.0004) and 

prolonged overall survival (11 months vs. 9 months, p= 0.01). 

 

During these two phase III studies, the safety profile of docetaxel was consistent with the safety profile 

observed in phase II studies (see section 4.8). 

 

An open-label,  multi centre, randomised phase III study was conducted to compare docetaxel 

monotherapy and paclitaxel in the treatment of advanced breast cancer in patients whose previous 

therapy should have included an anthracycline. A total of 449 patients were randomised to receive 

either docetaxel monotherapy 100 mg/m² as a 1 hour infusion or paclitaxel 175 mg/m² as a 3 hour 

infusion. Both regimens were administered every 3 weeks. 



124 

Without affecting the primary endpoint, overall response rate (32% vs 25%, p = 0.10), docetaxel 

prolonged median time to progression (24.6 weeks vs 15.6 weeks; p < 0.01) and median survival 

(15.3 months vs 12.7 months; p = 0.03). 

More grade 3/4 adverse events were observed for docetaxel monotherapy (55.4%) compared to 

paclitaxel (23.0%). 

 

DOCETAXEL KABI in combination with doxorubicin 

 

One large randomised phase III study, involving 429 previously untreated patients with metastatic 

disease, has been performed with doxorubicin (50 mg/m²) in combination with docetaxel (75 mg/m²) 

(AT arm) versus doxorubicin (60 mg/m²) in combination with cyclophosphamide (600 mg/m²) (AC 

arm). Both regimens were administered on day 1 every 3 weeks.  

• Time to progression (TTP) was significantly longer in the AT arm versus AC arm, p = 0.0138. 
The median TTP was 37.3 weeks (95% CI: 33.4 - 42.1) in AT arm and 31.9 weeks (95% CI: 27.4 - 

36.0) in AC arm.  

• Overall response rate (ORR) was significantly higher in the AT arm versus AC arm, p = 0.009. 
The ORR was 59.3% (95% CI: 52.8 - 65.9) in AT arm versus 46.5% (95% CI: 39.8 - 53.2) in AC 

arm.  

 

In this study, AT arm showed a higher incidence of severe neutropenia (90% versus 68.6%), febrile 

neutropenia (33.3% versus 10%), infection (8% versus 2.4%), diarrhoea (7.5% versus 1.4%), asthenia 

(8.5% versus 2.4%), and pain (2.8% versus 0%) than AC arm. On the other hand, AC arm showed a 

higher incidence of severe anaemia (15.8% versus 8.5%) than AT arm, and, in addition, a higher 

incidence of severe cardiac toxicity: congestive heart failure (3.8% versus 2.8%), absolute LVEF 

decrease ≥ 20% (13.1% versus 6.1%), absolute LVEF decrease ≥ 30% (6.2% versus 1.1%). Toxic 

deaths occurred in 1 patient in the AT arm (congestive heart failure) and in 4 patients in the AC arm 

(1 due to septic shock and 3 due to congestive heart failure).  

In both arms, quality of life measured by the EORTC questionnaire was comparable and stable during 

treatment and follow-up.  

 

DOCETAXEL KABI in combination with trastuzumab 

 

Docetaxel in combination with trastuzumab was studied for the treatment of patients with metastatic 

breast cancer whose tumours overexpress HER2, and who previously had not received chemotherapy 

for metastatic disease. One hundred eighty six patients were randomised to receive docetaxel 

(100 mg/m2) with or without trastuzumab; 60% of patients received prior anthracycline-based adjuvant 

chemotherapy. Docetaxel plus trastuzumab was efficacious in patients whether or not they had 

received prior adjuvant anthracyclines. The main test method used to determine HER2 positivity in 

this pivotal study was immunohistochemistry (IHC). A minority of patients were tested using 

fluorescence in-situ hybridization (FISH). In this study, 87% of patients had disease that was IHC 3+, 

and 95% of patients entered had disease that was IHC 3+ and/or FISH positive. Efficacy results are 

summarized in the following table:  

 

Parameter Docetaxel plus trastuzumab1 

n = 92 

Docetaxel1 

n = 94 

Response rate 

(95% CI) 

61% 

(50-71) 

34% 

(25-45) 

Median duration of response 

(months) 

(95% CI)  

11.4 

(9.2-15.0) 

5.1 

(4.4-6.2) 

Median TTP (months) 

(95% CI) 

10.6 

(7.6-12.9) 

5.7 

(5.0-6.5) 

Median survival (months) 

(95% CI) 

30.52 

(26.8-ne) 

22.12 

(17.6-28.9) 



125 

TTP = time to progression; “ne” indicates that it could not be estimated or it was not yet reached.  
1Full analysis set (intent-to-treat)  
2 Estimated median survival  

DOCETAXEL KABI in combination with capecitabine 

 

Data from one multi-centre, randomised, controlled phase III clinical study support the use of 

docetaxel in combination with capecitabine for treatment of patients with locally advanced or 

metastatic breast cancer after failure of cytotoxic chemotherapy, including an anthracycline. In this 

study, 255 patients were randomised to treatment with docetaxel (75 mg/m2 as a 1 hour intravenous 

infusion every 3 weeks) and capecitabine (1250 mg/m2 twice daily for 2 weeks followed by 1-week 

rest period). 256 patients were randomised to treatment with docetaxel alone (100 mg/m2 as a 1 hour 

intravenous infusion every 3 weeks). Survival was superior in the docetaxel + capecitabine 

combination arm (p = 0.0126). Median survival was 442 days (docetaxel + capecitabine) vs. 352 days 

(docetaxel alone). The overall objective response rates in the all-randomised population (investigator 

assessment) were 41.6% (docetaxel + capecitabine) vs. 29.7% (docetaxel alone); p = 0.0058. Time to 

progressive disease was superior in the docetaxel + capecitabine combination arm (p < 0.0001). The 

median time to progression was 186 days (docetaxel + capecitabine) vs. 128 days (docetaxel alone). 

 

Non-small cell lung cancer 

 

Patients previously treated with chemotherapy with or without radiotherapy 

 

In a phase III study, in previously treated patients, time to progression (12.3 weeks versus 7 weeks) 

and overall survival were significantly longer for docetaxel at 75 mg/m² compared to Best Supportive 

Care. The 1-year survival rate was also significantly longer in docetaxel (40%) versus BSC (16%). 

There was less use of morphinic analgesic (p < 0.01), non-morphinic analgesics (p < 0.01), other 

disease-related medicinal products (p = 0.06) and radiotherapy (p < 0.01) in patients treated with 

docetaxel at 75 mg/m² compared to those with BSC.  

The overall response rate was 6.8% in the evaluable patients, and the median duration of response was 

26.1 weeks.  

 

DOCETAXEL KABI in combination with platinum agents in chemotherapy-naïve patients 

 

In a phase III study, 1218 patients with unresectable stage IIIB or IV NSCLC, with KPS of 70% or 

greater, and who did not receive previous chemotherapy for this condition, were randomised to either 

docetaxel (T) 75 mg/m2 as a 1 hour infusion immediately followed by cisplatin (Cis) 75 mg/m2 over 

30-60 minutes every 3 weeks (TCis), docetaxel 75 mg/m2 as a 1 hour infusion in combination with 

carboplatin (AUC 6 mg/ml.min) over 30-60 minutes every 3 weeks, or vinorelbine (V) 25 mg/m2 

administered over 6-10 minutes on days 1, 8, 15, 22 followed by cisplatin 100 mg/m2 administered on 

day 1 of cycles repeated every 4 weeks (VCis).  

 

Survival data, median time to progression and response rates for two arms of the study are illustrated 

in the following table:  

 

 TCis 

n = 408 

VCis 

n = 404 

Statistical analysis 

Overall survival 

(Primary end-point): 

   

Median survival (months) 11.3 10.1 Hazard Ratio: 1.122 

 [97.2% CI: 0.937; 1.342]* 

1-year Survival (%) 46 41 Treatment difference: 5.4% 

[95% CI: -1.1; 12.0] 

2 year Survival (%) 21 14 Treatment difference: 6.2% 

[95% CI: 0.2; 12.3] 

Median time to progression 

(weeks): 

22.0 23.0 Hazard Ratio: 1.032  

[95% CI: 0.876; 1.216] 

Overall response rate (%): 31.6 24.5 Treatment difference: 7.1% 



126 

 TCis 

n = 408 

VCis 

n = 404 

Statistical analysis 

[95% CI: 0.7; 13.5] 

*: Corrected for multiple comparisons and adjusted for stratification factors (stage of disease and 

region of treatment), based on evaluable patient population. 

Secondary end-points included change of pain, global rating of quality of life by EuroQoL-5D, Lung 

Cancer Symptom Scale, and changes in Karnosfky performance status. Results on these end-points 

were supportive of the primary end-points results.  

 

For docetaxel/carboplatin combination, neither equivalent nor non-inferior efficacy could be proven 

compared to the reference treatment combination VCis.  

 

Prostate cancer 

Metastatic castration-resistant prostate cancer 

 

The safety and efficacy of docetaxel in combination with prednisone or prednisolone in patients with 

metastatic castration-resistant prostate cancer were evaluated in a randomised multi-centre phase III 

study (TAX 327). A total of 1006 patients with KPS ≥ 60 were randomised to the following treatment 

groups:  

• Docetaxel 75 mg/m2 every 3 weeks for 10 cycles. 

• Docetaxel 30 mg/m2 administered weekly for the first 5 weeks in a 6 week cycle for 5 cycles. 

• Mitoxantrone 12 mg/m2 every 3 weeks for 10 cycles. 
All 3 regimens were administered in combination with prednisone or prednisolone 5 mg twice daily, 

continuously. 

 

Patients who received docetaxel every three weeks demonstrated significantly longer overall survival 

compared to those treated with mitoxantrone. The increase in survival seen in the docetaxel weekly 

arm was not statistically significant compared to the mitoxantrone control arm. Efficacy endpoints for 

the docetaxel arms versus the control arm are summarized in the following table:  

 

Endpoint 

 

Docetaxel every 3 

weeks 

Docetaxel every 

week 

Mitoxantrone 

every 3 weeks 

Number of patients 

Median survival (months) 

95% CI 

Hazard ratio 

95% CI 

p-value† * 

335 

18.9 

(17.0-21.2) 

0.761 

(0.619-0.936) 

0.0094 

334 

17.4 

(15.7-19.0) 

0.912 

(0.747-1.113) 

0.3624 

337 

16.5 

(14.4-18.6) 

- 

- 

- 

Number of patients 

PSA** response rate (%) 

95% CI 

p-value* 

291 

45.4 

(39.5-51.3) 

0.0005 

282 

47.9 

(41.9-53.9) 

< 0.0001 

300 

31.7 

(26.4-37.3) 

- 

Number of patients 

Pain response rate (%) 

95% CI 

p-value* 

153 

34.6 

(27.1-42.7) 

0.0107 

154 

31.2 

(24.0-39.1) 

0.0798 

157 

21.7 

(15.5-28.9) 

- 

Number of patients 

Tumor response rate (%) 

95% CI 

p-value* 

141 

12.1 

(7.2-18.6) 

0.1112 

134 

8.2 

(4.2-14.2) 

0.5853 

137 

6.6 

(3.0-12.1) 

- 
†Stratified log-rank test  

*Threshold for statistical significance = 0.0175  

**PSA: Prostate-Specific Antigen  

 



127 

Given the fact that docetaxel every week presented a slightly better safety profile than docetaxel every 

3 weeks, it is possible that certain patients may benefit from docetaxel every week.  

 

No statistical differences were observed between treatment groups for Global Quality of Life. 

 

Metastatic hormone-sensitive prostate cancer 

 

STAMPEDE study 

 

The safety and efficacy of docetaxel administered concomitantly with standard of care (ADT) in 

patients with high-risk locally advanced or metastatic hormone-sensitive prostate cancer were 

evaluated in a randomised multi-centre, multi-arm multi-stage (MAMS) study with a seamless phase 

II/III design (STAMPEDE – MRC PR08). A total of 1776 male patients were allocated to the 
treatment arms of interest:  

• Standard of care + docetaxel 75 mg/m², administered every 3 weeks for 6 cycles 

• Standard of care alone  

Docetaxel regimen was administered in combination with prednisone or prednisolone 5 mg twice daily 

continuously.  

Among the 1776 randomised patients 1086 (61%) had metastatic disease, 362 were randomised to 

docetaxel in combination with standard of care, 724 received standard of care alone.  

 

In these metastatic prostate cancer patients, the median overall survival was significantly longer in 

docetaxel treatment groups than in the standard of care alone group, with a median overall survival 19 

months longer with the addition of docetaxel to standard of care (HR =  0.76, 95% CI = 0.62-0.92, 

p=0.005).  

 

Efficacy results in metastatic prostate cancer patients for docetaxel arm versus control arm are 

summarized in the following table: 

 

Efficacy of docetaxel in combination with prednisone or prednisolone and standard of care in the 

treatment of patients with metastatic hormone-sensitive prostate cancer (STAMPEDE) 

 

Endpoint 

 

Docetaxel + standard of care 

 

Standard of care alone 

Number of metastatic prostate 

cancer patients 

 

Median overall survival (months)  

95% CI 

362 

 

 

62 

51-73 

724 

 

 

43 

40-48 

Adjusted hazard ratio 

95% CI 

p-valuea 

0.76 

(0.62-0.92) 

0.005 

Failure-Free survivalb    

Median (months) 

95% CI 

20.4 

16.8-25.2 

12 

9.6-12 

Adjusted hazard ratio 

95% CI 

p-valuea 

0.66 

(0.57-0.76) 

< 0.001 



128 

a p-value calculated from the likelihood ratio test and adjusted for all stratification factors 

(except center and planned hormone therapy) and stratified by trial period 
b Failure-free survival: time from randomization to first evidence of at least one of: biochemical 

failure (defined as a rise in PSA of 50% above the within-24-week nadir and above 4 ng/mL 

and confirmed by retest or treatment); progression either locally, in lymph nodes, or in distant 

metastases; skeletal-related event; or death from prostate cancer. 

 

CHAARTED study 

 

The safety and efficacy of docetaxel administered at the beginning of androgen-deprivation therapy 

(ADT) in patients with metastatic hormone-sensitive prostate cancer were evaluated in a randomised 

Phase III multi-centre study (CHAARTED). A total of 790 male patients were allocated to the 2 

treatment groups.  

• ADT + docetaxel 75 mg/m² given at the beginning of ADT, administered every 3 weeks 

for 6 cycles 

• ADT alone   

 

The median overall survival was significantly longer in docetaxel treatment group than in the ADT 

alone group, with a median overall survival 13.6 months longer with the addition of docetaxel to ADT 

(hazard ratio (HR) = 0.61, 95% confidence interval (CI) = 0.47-0.80, p=0.0003).  

 

Efficacy results or the docetaxel arm versus the control arm are summarized in the following table: 

 

Efficacy of docetaxel and ADT in the treatment of patients with metastatic hormone-sensitive prostate 

cancer (CHAARTED) 

 

Endpoint 

 

Docetaxel +ADT  

 

ADT alone 

Number of patients 

Median overall survival (months) 

All patients 

95% CIAdjusted hazard ratio 

397 

 

57.6 

49.1-72.8 

0.61 

393 

 

44.0 

34.4-49.1 

-- 

95% CI (0.47-0.80)  -- 

p-valuea 0.0003 -- 

Progression Free Survival 

Median (months) 

95% CI 

Adjusted hazard ratio 
95% CI 

p-value* 

 

19.8 

16.7-22.8 

0.60 

0.51-0.72 

P<0.0001 

 

11.6 

10.8-14.3 

-- 

-- 

-- 

PSA response** at 6 months – N(%) 

p-valuea* 

127 (32.0) 

<0.0001 

77 (19.6) 

-- 

PSA response** at 12 months – N(%) 

p-valuea* 

110 (27.7) 

<0.0001 

66 (16.8) 

-- 

Time to castration-resistant prostate cancerb   

Median (months)  

95% CI 

Adjusted hazard ratio 

20.2 

(17.2-23.6) 

0.61 

11.7 

(10.8-14.7) 

-- 

95% CI (0.51-0.72) -- 

p-valuea* <0.0001 -- 

Time to clinical progressionc    

Median (months)  33.0 19.8 



129 

Endpoint 

 

Docetaxel +ADT  

 

ADT alone 

95% CI (27.3-41.2) (17.9-22.8) 

Adjusted hazard ratio 0.61 -- 

95% CI (0.50-0.75) -- 

p-valuea* <0.0001 -- 

a Time to event variables: Stratified log-rank test.  

  Response rate variables: Fisher's Exact test  

* p-value for descriptive purpose. 

** PSA response: Prostate-Specific Antigen response: PSA level <0.2 ng/mL measured for two 

consecutive measurements at least 4 weeks apart. 

b Time to castration-resistant prostate cancer = time from randomization to PSA progression or 

clinical progression (i.e., increasing symptomatic bone metastases, progression per Response 

Evaluation Criteria in Solid Tumours (RECIST) criteria, or clinical deterioration due to cancer 

per the Investigator’s opinion), whichever occurred first. 
c The time to clinical progression = the time from randomization until clinical progression (i.e., 

increased symptoms of bone metastases; progression according to RECIST; or clinical deterioration 

due to cancer according to the investigator’s opinion). 

 

Gastric adenocarcinoma 

 

A multi-centre, open-label, randomised study, was conducted to evaluate the safety and efficacy of 

docetaxel for the treatment of patients with metastatic gastric adenocarcinoma, including 

adenocarcinoma of the gastroesophageal junction, who had not received prior chemotherapy for 

metastatic disease. A total of 445 patients with KPS > 70 were treated with either docetaxel (T) 

(75 mg/m2 on day 1) in combination with cisplatin (C) (75 mg/m2 on day 1) and 5-fluorouracil (F) 

(750 mg/m2 per day for 5 days) or cisplatin (100 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2 per 

day for 5 days). The length of a treatment cycle was 3 weeks for the TCF arm and 4 weeks for the CF 

arm. The median number of cycles administered per patient was 6 (with a range of 1-16) for the TCF 

arm compared to 4 (with a range of 1-12) for the CF arm. Time to progression (TTP) was the primary 

endpoint. The risk reduction of progression was 32.1% and was associated with a significantly longer 

TTP (p = 0.0004) in favour of the TCF arm. Overall survival was also significantly longer 

(p = 0.0201) in favour of the TCF arm with a risk reduction of mortality of 22.7%. Efficacy results are 

summarized in the following table: 

 

Efficacy of docetaxel in the treatment of patients with gastric adenocarcinoma 

 

Endpoint TCF 

n = 221 

CF 

n = 224 

Median TTP (months) 

(95% CI) 

Hazard ratio 

(95% CI) 

*p-value 

5.6 

(4.86-5.91) 

3.7 

(3.45-4.47) 

1.473 

(1.189-1.825) 

0.0004 

Median survival (months) 

(95% CI) 

2-year estimate (%) 

Hazard ratio 

(95% CI) 

*p-value 

9.2 

(8.38-10.58) 

18.4 

8.6 

(7.16-9.46) 

8.8 

1.293 

(1.041-1.606) 

0.0201 

Overall Response Rate (CR+PR) (%) 36.7 25.4 



130 

Endpoint TCF 

n = 221 

CF 

n = 224 

p-value 0.0106 

Progressive Disease as Best Overall Response (%) 16.7 25.9 

*Unstratified logrank test  

Subgroup analyses across age, gender and race consistently favoured the TCF arm compared to the CF 

arm.  

 

A survival update analysis conducted with a median follow-up time of 41.6 months no longer showed 

a statistically significant difference although always in favour of the TCF regimen and showed that the 

benefit of TCF over CF is clearly observed between 18 and 30 months of follow up.  

 

Overall, quality of life (QoL) and clinical benefit results consistently indicated improvement in favour 

of the TCF arm. Patients treated with TCF had a longer time to 5% definitive deterioration of global 

health status on the QLQ-C30 questionnaire (p = 0.0121) and a longer time to definitive worsening of 

Karnofsky performance status (p = 0.0088) compared to patients treated with CF. 

 

Head and neck cancer 

 

• Induction chemotherapy followed by radiotherapy (TAX323)  
The safety and efficacy of docetaxel in the induction treatment of patients with squamous cell 

carcinoma of the head and neck (SCCHN) was evaluated in a phase III, multi-centre, open-label, 

randomised study (TAX323). In this study, 358 patients with inoperable locally advanced SCCHN, 

and WHO performance status 0 or 1, were randomised to one of two treatment arms. Patients on the 

docetaxel arm received docetaxel (T) 75 mg/m2 followed by cisplatin (P) 75 mg/m2 followed by 

5-fluorouracil (F) 750 mg/m2 per day as a continuous infusion for 5 days. This regimen was 

administered every three weeks for 4 cycles in case at least a minor response (≥ 25% reduction in 

bidimensionally measured tumour size) was observed after 2 cycles. At the end of chemotherapy, with 

a minimal interval of 4 weeks and a maximal interval of 7 weeks, patients whose disease did not 

progress received radiotherapy (RT) according to institutional guidelines for 7 weeks (TPF/RT). 

Patients on the comparator arm received cisplatin (P) 100 mg/m2 followed by 5-fluorouracil (F) 

1000 mg/m2 per day for 5 days. This regimen was administered every three weeks for 4 cycles in case 

at least a minor response (≥ 25% reduction in bidimensionally measured tumour size) was observed 

after 2 cycles. At the end of chemotherapy, with a minimal interval of 4 weeks and a maximal interval 

of 7 weeks, patients whose disease did not progress received radiotherapy (RT) according to 

institutional guidelines for 7 weeks (PF/RT). Locoregional therapy with radiation was delivered either 

with a conventional fraction (1.8 Gy - 2.0 Gy once a day, 5 days per week for a total dose of 66 to 

70 Gy), or accelerated/hyperfractionated regimens of radiation therapy (twice a day, with a minimum 

interfraction interval of 6 hours, 5 days per week). A total of 70 Gy was recommended for accelerated 

regimens and 74 Gy for hyperfractionated schemes. Surgical resection was allowed following 

chemotherapy, before or after radiotherapy. Patients on the TPF arm received antibiotic prophylaxis 

with ciprofloxacin 500 mg orally twice daily for 10 days starting on day 5 of each cycle, or equivalent. 

The primary endpoint in this study, progression-free survival (PFS), was significantly longer in the 

TPF arm compared to the PF arm, p = 0.0042 (median PFS: 11.4 vs. 8.3 months respectively) with an 

overall median follow up time of 33.7 months. Median overall survival was also significantly longer in 

favour of the TPF arm compared to the PF arm (median OS: 18.6 vs. 14.5 months respectively) with a 

28% risk reduction of mortality, p = 0.0128. Efficacy results are presented in the table below:  

 

Efficacy of docetaxel in the induction treatment of patients with inoperable locally advanced SCCHN 

(Intent-to-Treat Analysis) 

 

 

 



131 

Endpoint Docetaxel + 

Cis + 5-FU 

n = 177 

Cis + 5-FU 

 

n = 181 

Median progression free survival (months) 

(95% CI) 

Adjusted Hazard ratio 

(95% CI) 

*p-value 

11.4 

(10.1-14.0) 

8.3 

(7.4-9.1) 

0.70 

(0.55-0.89) 

0.0042 

Median survival (months) 

(95% CI) 

Hazard ratio 

(95% CI) 

**p-value 

18.6 

(15.7-24.0) 

14.5 

(11.6-18.7) 

0.72 

(0.56-0.93) 

0.0128 

Best overall response to chemotherapy (%) 

(95% CI)  

***p-value 

67.8 

(60.4-74.6) 

53.6 

(46.0-61.0) 

0.006 

Best overall response to study treatment [chemotherapy 

+/- radiotherapy] (%) 

(95% CI)  

***p-value 

72.3 

(65.1-78.8) 

58.6 

(51.0-65.8) 

0.006 

 Median duration of response to chemotherapy ± 

radiotherapy (months) 

(95% CI)  

Hazard ratio 

(95% CI) 

**p-value 

n = 128 

15.7 

(13.4-24.6) 

n = 106 

11.7 

(10.2-17.4) 

0.72 

(0.52-0.99) 

0.0457 

A hazard ratio of less than 1 favours docetaxel + cisplatin + 5-FU 

*Cox model (adjustment for Primary tumour site, T and N clinical stages and PSWHO) 

**Logrank test  

*** Chi-square test  

 

Quality of life parameters 

 

Patients treated with TPF experienced significantly less deterioration of their Global health score 

compared to those treated with PF (p = 0.01, using the EORTC QLQ-C30 scale). 

 

Clinical benefit parameters 

 

The performance status scale, for head and neck (PSS-HN) subscales designed to measure 

understandability of speech, ability to eat in public, and normalcy of diet, was significantly in favour 

of TPF as compared to PF. 

Median time to first deterioration of WHO performance status was significantly longer in the TPF arm 

compared to PF. Pain intensity score improved during treatment in both groups indicating adequate 

pain management.  

 

• Induction chemotherapy followed by chemoradiotherapy (TAX324)  
The safety and efficacy of docetaxel in the induction treatment of patients with locally advanced 

squamous cell carcinoma of the head and neck (SCCHN) was evaluated in a randomised ,multi-centre 
open-label, phase III, study (TAX324). In this study, 501 patients, with locally advanced SCCHN, and 

a WHO performance status of 0 or 1, were randomised to one of two arms. The study population 

comprised patients with technically unresectable disease, patients with low probability of surgical cure 



132 

and patients aiming at organ preservation. The efficacy and safety evaluation solely addressed survival 

endpoints and the success of organ preservation was not formally addressed. Patients on the docetaxel 

arm received docetaxel (T) 75 mg/m² by intravenous infusion on day 1 followed by cisplatin (P) 

100 mg/m² administered as a 30-minute to three-hour intravenous infusion, followed by the continuous 

intravenous infusion of 5-fluorouracil (F) 1000 mg/m²/day from day 1 to day 4. The cycles were 

repeated every 3 weeks for 3 cycles. All patients who did not have progressive disease were to receive 

chemoradiotherapy (CRT) as per protocol (TPF/CRT). Patients on the comparator arm received 

cisplatin (P) 100 mg/m² as a 30-minute to three-hour intravenous infusion on day 1 followed by the 

continuous intravenous infusion of 5-fluorouracil (F) 1000 mg/m²/day from day 1 to day 5. The cycles 

were repeated every 3 weeks for 3 cycles. All patients who did not have progressive disease were to 

receive CRT as per protocol (PF/CRT).  

Patients in both treatment arms were to receive 7 weeks of CRT following induction chemotherapy 

with a minimum interval of 3 weeks and no later than 8 weeks after start of the last cycle (day 22 to 

day 56 of last cycle). During radiotherapy, carboplatin (AUC 1.5) was given weekly as a one-hour 

intravenous infusion for a maximum of 7 doses. Radiation was delivered with megavoltage equipment 

using once daily fractionation (2 Gy per day, 5 days per week for 7 weeks, for a total dose of 

70-72 Gy). Surgery on the primary site of disease and/or neck could be considered at anytime 

following completion of CRT. All patients on the docetaxel-containing arm of the study received 

prophylactic antibiotics. The primary efficacy endpoint in this study, overall survival (OS) was 

significantly longer (log-rank test, p = 0.0058) with the docetaxel-containing regimen compared to PF 

(median OS: 70.6 versus 30.1 months respectively), with a 30% risk reduction in mortality compared 

to PF (hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.54-0.90) with an overall median 

follow up time of 41.9 months. The secondary endpoint, PFS, demonstrated a 29% risk reduction of 

progression or death and a 22 month improvement in median PFS (35.5 months for TPF and 13.1 for 

PF). This was also statistically significant with an HR of 0.71; 95% CI 0.56-0.90; log-rank test 

p = 0.004. Efficacy results are presented in the table below: 

 

Efficacy of docetaxel in the induction treatment of patients with locally advanced SCCHN (Intent-to-

Treat Analysis) 

 

Endpoint Docetaxel + Cis + 5-FU 

n = 255 

Cis + 5-FU 

n = 246 

Median overall survival (months) 

(95% CI) 

Hazard ratio: 

(95% CI) 

*p-value  

70.6 

(49.0-NA) 

30.1 

(20.9-51.5) 

0.70 

(0.54-0.90) 

0.0058 

Median PFS (months) 

(95% CI) 

Hazard ratio: 

(95% CI) 

**p-value  

35.5 

(19.3-NA) 

13.1 

(10.6-20.2) 

0.71 

(0.56 - 0.90) 

0.004 

Best overall response (CR + PR) to 

chemotherapy (%) 

(95% CI)  

***p-value 

71.8 

(65.8-77.2) 

64.2 

(57.9-70.2) 

0.070 

Best overall response (CR + PR) to study 

treatment [chemotherapy +/- 

chemoradiotherapy] (%) 

(95% CI) 

***p-value 

 

76.5 

(70.8-81.5) 

 

71.5 

(65.5-77.1) 

0.209 

A hazard ratio of less than 1 favours docetaxel + cisplatin + fluorouracil  

*un-adjusted log-rank test  



133 

**un-adjusted log-rank test, not adjusted for multiple comparisons  

***Chi square test, not adjusted for multiple comparisons  

NA-not applicable 

 

 

5.2 Pharmacokinetic properties 

 

Absorption 

 

The pharmacokinetics of docetaxel have been evaluated in cancer patients after administration of 20-

115 mg/m2 in phase I studies. The kinetic profile of docetaxel is dose independent and consistent with 

a three-compartment pharmacokinetic model with half lives for the α, β and γ phases of 4 min, 36 min 

and 11.1 h, respectively. The late phase is due, in part, to a relatively slow efflux of docetaxel from the 

peripheral compartment. 

 

Distribution 

 

Following the administration of a 100 mg/m2 dose given as a one-hour infusion a mean peak plasma 

level of 3.7 μg/ml was obtained with a corresponding AUC of 4.6 h.μg/ml. Mean values for total body 

clearance and steady-state volume of distribution were 21 l/h/m2 and 113 l, respectively. Inter 

individual variation in total body clearance was approximately 50%. Docetaxel is more than 95% 

bound to plasma proteins.  

 

Elimination 

 

A study of 14C-docetaxel has been conducted in three cancer patients. Docetaxel was eliminated in 

both the urine and faeces following cytochrome P450-mediated oxidative metabolism of the tert-butyl 

ester group, within seven days, the urinary and faecal excretion accounted for about 6% and 75% of 

the administered radioactivity, respectively. About 80% of the radioactivity recovered in faeces is 

excreted during the first 48 hours as one major inactive metabolite and 3 minor inactive metabolites 

and very low amounts of unchanged medicinal product.  

 

Special populations 

 

Age and gender 

A population pharmacokinetic analysis has been performed with docetaxel in 577 patients. 

Pharmacokinetic parameters estimated by the model were very close to those estimated from phase I 

studies. The pharmacokinetics of docetaxel were not altered by the age or sex of the patient. 

 

Hepatic impairment 

In a small number of patients (n = 23) with clinical chemistry data suggestive of mild to moderate liver 

function impairment (ALT, AST ≥ 1.5 times the ULN associated with alkaline phosphatase ≥ 2.5 

times the ULN), total clearance was lowered by 27% on average (see section 4.2). 

 

Fluid retention 

Docetaxel clearance was not modified in patients with mild to moderate fluid retention and there are 

no data available in patients with severe fluid retention. 

 

Combination therapy 

 

Doxorubicin 

When used in combination, docetaxel does not influence the clearance of doxorubicin and the plasma 

levels of doxorubicinol (a doxorubicin metabolite). The pharmacokinetics of docetaxel, doxorubicin 

and cyclophosphamide were not influenced by their co-administration.  

 

 

 



134 

Capecitabine 

Phase I study evaluating the effect of capecitabine on the pharmacokinetics of docetaxel and vice versa 

showed no effect by capecitabine on the pharmacokinetics of docetaxel (Cmax and AUC) and no 

effect by docetaxel on the pharmacokinetics of a relevant capecitabine metabolite 5'-DFUR.  

 

Cisplatin 

Clearance of docetaxel in combination therapy with cisplatin was similar to that observed following 

monotherapy. The pharmacokinetic profile of cisplatin administered shortly after docetaxel infusion is 

similar to that observed with cisplatin alone.  

 

Cisplatin and 5-fluorouracil 

The combined administration of docetaxel, cisplatin and 5-fluorouracil in 12 patients with solid 

tumours had no influence on the pharmacokinetics of each individual medicinal product.  

 

Prednisone and dexamethasone 

The effect of prednisone on the pharmacokinetics of docetaxel administered with standard 

dexamethasone premedication has been studied in 42 patients. 

 

Prednisone 

No effect of prednisone on the pharmacokinetics of docetaxel was observed. 

 

 

5.3  Preclinical safety data 

 

The carcinogenic potential of docetaxel has not been studied. 

Docetaxel has been shown to be mutagenic in the in vitro micronucleus and chromosome aberration 

test in CHO-K1 cells and in the in vivo micronucleus test in the mouse. However, it did not induce 

mutagenicity in the Ames test or the CHO/HGPRT gene mutation assay. These results are consistent 

with the pharmacological activity of docetaxel.  

 

It was shown that docetaxel was embryotoxic and fetotoxic in rats and rabbits. Undesirable effects on 

the testis observed in rodent toxicity studies suggest that docetaxel may impair male fertility. 

 

 

6. PHARMACEUTICAL PARTICULARS 
 

6.1 List of excipients 

 

Polysorbate 80 

Ethanol anhydrous 

Anhydrous citric acid (pH adjustment) 

 

 

6.2 Incompatibilities 

 

This medicinal product must not be mixed with other medicinal products except those mentioned in 

section 6.6. 

 

 

6.3 Shelf life 

 

Unopened vial 

2 years. 

 

After opening of the vial 

Each vial is for single use and should be used immediately after opening. If not used immediately, 

in-use storage times and conditions are the responsibility of the user. 



135 

 

Once added to the infusion bag 

From a microbiological point of view, reconstitution/dilution must take place in controlled and aseptic 

conditions and the medicinal product should be used immediately. If not used immediately, in-use 

storage times and conditions are the responsibility of the user. 

 

Once added as recommended into the infusion bag, the docetaxel infusion solution, if stored below 

25°C, is stable for 6 hours. It should be used within 6 hours (including the one hour infusion 

intravenous administration). 

 

In addition, physical and chemical in-use stability of the infusion solution prepared as recommended 

has been demonstrated in non-PVC bags up to 48 hours when stored between 2 to 8°C. 

 

 

6.4 Special precautions for storage 

 

Do not store above 25°C.  

Store in the original package in order to protect from light.  

 

For storage conditions of the diluted medicinal product, see section 6.3. 

 

 

6.5 Nature and contents of container 

 

6 ml clear, colourless Type-I glass vial, closed with flurotec rubber stopper and a red flip-off 

aluminium over seal containing 6 ml of concentrate. 

 

Each box contains one vial. 

 

 

6.6 Special precautions for disposal and other handling 

 

DOCETAXEL KABI is an antineoplastic agent and, as with other potentially toxic compounds, 

caution should be exercised when handling it and preparing the solution. The use of gloves is 

recommended. 

 

If DOCETAXEL KABI concentrate or infusion solution should come into contact with skin, wash 

immediately and thoroughly with soap and water. If DOCETAXEL KABI concentrate or infusion 

solution should come into contact with mucous membranes, wash immediately and thoroughly with 

water. 

 

Preparation for the intravenous administration 

 

Preparation of the infusion solution 

DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 

with this medicinal product (DOCETAXEL KABI 120 mg/6 ml concentrate for solution for 

infusion, which contains only 1 vial). 

 

DOCETAXEL KABI 120 mg/6 ml concentrate for solution for infusion requires NO prior 

dilution with a solvent and is ready to add to the infusion solution. 

 

Each vial is for single use and should be used immediately. 

 

If the vials are stored under refrigeration, allow the required number of boxes of DOCETAXEL KABI 

concentrate for solution for infusion to stand below 25°C for 5 minutes before use. More than one vial 

of DOCETAXEL KABI concentrate for solution for infusion may be necessary to obtain the required 



136 

dose for the patient. Aseptically withdraw the required amount of DOCETAXEL KABI concentrate 

for solution for infusion using a calibrated syringe.  

 

In DOCETAXEL KABI 120 mg/6 ml vial the concentration of docetaxel is 20 mg/ml. 

The required volume of DOCETAXEL KABI concentrate for solution for infusion must be injected 

via a single injection (one shot) into a 250 ml infusion bag or bottle containing either 5% glucose 

solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. 

 

If a dose greater than 190 mg of docetaxel is required, use a larger volume of the infusion vehicle so 

that a concentration of 0.74 mg/ml docetaxel is not exceeded. 

 

Mix the infusion bag or bottle manually using a rocking motion. 

 

The infusion bag solution should be used within 6 hours below 25°C including the one hour infusion 

to the patient. 

 

As with all parenteral products, DOCETAXEL KABI infusion solution should be visually inspected 

prior to use, and solutions containing a precipitate should be discarded. 

 

Docetaxel infusion solution is supersaturated, therefore may crystallize over time. If crystals appear, 

the solution must no longer be used and shall be discarded. 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

 

Fresenius Kabi Deutschland GmbH 

Else-Kröner-Straße 1, 

61352 Bad Homburg v.d.Höhe 

Germany 

 

 

8. MARKETING AUTHORISATION NUMBER 
 

EU/1/12/770/002 

 
 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 22nd May 2012 

Date of latest renewal: 23 February 2017 

 

 

10. DATE OF REVISION OF THE TEXT 
 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu  



137 

1. NAME OF THE MEDICINAL PRODUCT 
 

DOCETAXEL KABI 160 mg/8 ml concentrate for solution for infusion 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each ml of concentrate contains 20 mg docetaxel anhydrous. 

 

One vial of 8 ml of concentrate contains 160 mg of docetaxel. 

 

Excipient with known effect 

Each vial of concentrate contains 4 ml of ethanol anhydrous (3.16 g). 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Concentrate for solution for infusion (sterile concentrate). 

 

The concentrate is a clear, colourless to pale yellow solution. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 

 

Breast cancer 

 

DOCETAXEL KABI in combination with doxorubicin and cyclophosphamide is indicated for the 

adjuvant treatment of patients with: 

• operable node-positive breast cancer 

• operable node-negative breast cancer. 
 

For patients with operable node-negative breast cancer, adjuvant treatment should be restricted to 

patients eligible to receive chemotherapy according to internationally established criteria for primary 

therapy of early breast cancer (see section 5.1). 

DOCETAXEL KABI in combination with doxorubicin is indicated for the treatment of patients with 

locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for 

this condition. 

 

DOCETAXEL KABI monotherapy is indicated for the treatment of patients with locally advanced or 

metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have 

included an anthracycline or an alkylating agent. 

 

DOCETAXEL KABI in combination with trastuzumab is indicated for the treatment of patients with 

metastatic breast cancer whose tumours over express HER2 and who previously have not received 

chemotherapy for metastatic disease. 

 

DOCETAXEL KABI in combination with capecitabine is indicated for the treatment of patients with 

locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy 

should have included an anthracycline. 



138 

Non-small cell lung cancer 
 

DOCETAXEL KABI is indicated for the treatment of patients with locally advanced or metastatic 

non-small cell lung cancer after failure of prior chemotherapy. 

 

DOCETAXEL KABI in combination with cisplatin is indicated for the treatment of patients with 

unresectable, locally advanced or metastatic non-small cell lung cancer, in patients who have not 

previously received chemotherapy for this condition. 

 

Prostate cancer 

 

DOCETAXEL KABI in combination with prednisone or prednisolone is indicated for the treatment of 

patients with castration-resistant metastatic prostate cancer. 
 

DOCETAXEL KABI in combination with androgen-deprivation therapy (ADT), with or without 

prednisone or prednisolone, is indicated for the treatment of patients with metastatic hormone-

sensitive prostate cancer. 

 

Gastric adenocarcinoma 

 

DOCETAXEL KABI in combination with cisplatin and 5-fluorouracil is indicated for the treatment of 

patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal 

junction, who have not received prior chemotherapy for metastatic disease. 

 

Head and neck cancer 

 

DOCETAXEL KABI in combination with cisplatin and 5-fluorouracil is indicated for the induction 

treatment of patients with locally advanced squamous cell carcinoma of the head and neck. 

 

 

4.2 Posology and method of administration 

 

The use of docetaxel should be confined to units specialised in the administration of cytotoxic 

chemotherapy and it should only be administered under the supervision of a physician qualified in the 

use of anticancer chemotherapy (see section 6.6). 

 

Posology 

For breast, non-small cell lung, gastric, and head and neck cancers, premedication consisting of an oral 

corticosteroid, such as dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to 

docetaxel administration, unless contraindicated, can be used (see section 4.4).  

For metastatic castration-resistant prostate cancer, given the concurrent use of prednisone or 

prednisolone the recommended premedication regimen is oral dexamethasone 8 mg, 12 hours, 3 hours 

and 1 hour before the docetaxel infusion (see section 4.4). 

For metastatic hormone-sensitive prostate cancer, irrespective of the concurrent use of prednisone or 

prednisolone, the recommended premedication regimen is oral dexamethasone 8 mg 12 hours, 3 hours, 

and 1 hour before docetaxel infusion (see section 4.4). 

 

Prophylactic G-CSF may be used to mitigate the risk of haematological toxicities. 

 

Docetaxel is administered as a one-hour infusion every three weeks.  

 

Breast cancer 

In the adjuvant treatment of operable node-positive and node-negative breast cancer, the recommended 

dose of docetaxel is 75 mg/m2 administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 

500 mg/m2 every 3 weeks for 6 cycles (TAC regimen) (see also Dose adjustments during treatment). 

For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose 



139 

of docetaxel is 100 mg/m2 in monotherapy. In first-line treatment, docetaxel 75 mg/m2 is given in 

combination therapy with doxorubicin (50 mg/m2). 

 

In combination with trastuzumab the recommended dose of docetaxel is 100 mg/m2 every three weeks, 

with trastuzumab administered weekly. In the pivotal study the initial docetaxel infusion was started 

the day following the first dose of trastuzumab. The subsequent docetaxel doses were administered 

immediately after completion of the trastuzumab infusion, if the preceding dose of trastuzumab was 

well tolerated. For trastuzumab dose and administration, see trastuzumab summary of product 

characteristics.  

 

In combination with capecitabine, the recommended dose of docetaxel is 75 mg/m2 every three weeks, 

combined with capecitabine at 1250 mg/m2 twice daily (within 30 minutes after a meal) for 2 weeks 

followed by 1-week rest period. For capecitabine dose calculation according to body surface area, see 

capecitabine summary of product characteristics.  

 

Non-small cell lung cancer 

In chemotherapy naïve patients treated for non-small cell lung cancer, the recommended dose regimen 

is docetaxel 75 mg/m2 immediately followed by cisplatin 75 mg/m2 over 30-60 minutes. For treatment 

after failure of prior platinum-based chemotherapy, the recommended dose is 75 mg/m² as a single 

agent. 

 

Prostate cancer 

Prostate cancer Metastatic castration-resistant prostate cancer  
The recommended dose of docetaxel is 75 mg/m2. Prednisone or prednisolone 5 mg orally twice daily 

is administered continuously (see section 5.1). 

 

Metastatic hormone-sensitive prostate cancer 

The recommended dose of docetaxel is 75 mg/m2 every 3 weeks for 6 cycles. Prednisone or 

prednisolone 5 mg orally twice daily may be administered continuously. 

 

Gastric adenocarcinoma 

The recommended dose of docetaxel is 75 mg/m2 as a 1-hour infusion, followed by cisplatin 

75 mg/m2, as a 1- to 3- hour infusion (both on day 1 only), followed by 5-fluorouracil 750 mg/m2 per 

day given as a 24-hour continuous infusion for 5 days, starting at the end of the cisplatin infusion. 

Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and 

appropriate hydration for cisplatin administration. Prophylactic G-CSF should be used to mitigate the 

risk of haematological toxicities (see also Dose adjustments during treatment). 

 

Head and neck cancer 

Patients must receive premedication with antiemetics and appropriate hydration (prior to and after 

cisplatin administration). Prophylactic G-CSF may be used to mitigate the risk of haematological 

toxicities. All patients on the docetaxel-containing arm of the TAX 323 and TAX 324 studies, received 

prophylactic antibiotics. 

 

• Induction chemotherapy followed by radiotherapy (TAX 323) 
For the induction treatment of inoperable locally advanced squamous cell carcinoma of the head 

and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m2 as a 1 hour infusion 

followed by cisplatin 75 mg/m2 over 1 hour, on day one, followed by 5-fluorouracil as a 

continuous infusion at 750 mg/m2 per day for five days. This regimen is administered every 

3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy. 

 

• Induction chemotherapy followed by chemoradiotherapy (TAX 324) 
For the induction treatment of patients with locally advanced (technically unresectable, low 

probability of surgical cure, and aiming at organ preservation) squamous cell carcinoma of the 

head and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m2 as a 1 hour 

intravenous infusion on day 1, followed by cisplatin 100 mg/m2 administered as a 30-minute to 

3-hour infusion, followed by 5-fluorouracil 1000 mg/m2/day as a continuous infusion from day 1 



140 

to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, 

patients should receive chemoradiotherapy. 

 

For cisplatin and 5-fluorouracil dose modifications, see the corresponding summary of product 

characteristics. 

 

Dose adjustments during treatment 

 

General 

Docetaxel should be administered when the neutrophil count is ≥ 1,500 cells/mm3. 

In patients who experienced either febrile neutropenia, neutrophil count < 500 cells/mm3 for more than 

one week, severe or cumulative cutaneous reactions or severe peripheral neuropathy during docetaxel 

therapy, the dose of docetaxel should be reduced from 100 mg/m2 to 75 mg/m2 and/or from 75 to 

60 mg/m². If the patient continues to experience these reactions at 60 mg/m², the treatment should be 

discontinued. 

 

Adjuvant therapy for breast cancer 

Primary G-CSF prophylaxis should be considered in patients who receive docetaxel, doxorubicin and 

cyclophosphamide (TAC) adjuvant therapy for breast cancer. Patients who experience febrile 

neutropenia and/or neutropenic infection should have their docetaxel dose reduced to 60 mg/m² in all 

subsequent cycles (see sections 4.4 and 4.8). Patients who experience Grade 3 or 4 stomatitis should 

have their dose decreased to 60 mg/m². 

 

In combination with cisplatin 

For patients who are dosed initially at docetaxel 75 mg/m2 in combination with cisplatin and whose 

nadir of platelet count during the previous course of therapy is < 25,000 cells/mm3, or in patients who 

experience febrile neutropenia, or in patients with serious non-haematologic toxicities, the docetaxel 

dose in subsequent cycles should be reduced to 65 mg/m2. For cisplatin dose adjustments, see the 

corresponding summary of product characteristics.  

 

In combination with capecitabine 

• For capecitabine dose modifications, see capecitabine summary of product characteristics. 

• For patients developing the first appearance of Grade 2 toxicity, which persists at the time of the 
next docetaxel/capecitabine treatment, delay treatment until resolved to Grade 0-1, and resume at 

100% of the original dose. 

• For patients developing the second appearance of Grade 2 toxicity, or the first appearance of 
Grade 3 toxicity, at any time during the treatment cycle, delay treatment until resolved to Grade 

0-1 and then resume treatment with docetaxel 55 mg/m². 

• For any subsequent appearances of toxicities, or any Grade 4 toxicities, discontinue the docetaxel 
dose. 

 

For trastuzumab dose modifications, see trastuzumab summary of product characteristics. 

 

In combination with cisplatin and 5-fluorouracil 

If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite 

G-CSF use, the docetaxel dose should be reduced from 75 to 60 mg/m2. If subsequent episodes of 

complicated neutropenia occur the docetaxel dose should be reduced from 60 to 45 mg/m2. In case of 

Grade 4 thrombocytopenia the docetaxel dose should be reduced from 75 to 60 mg/m2. Patients should 

not be retreated with subsequent cycles of docetaxel until neutrophils recover to a level 

>1,500 cells/mm3 and platelets recover to a level >100,000 cells/mm3. Discontinue treatment if these 

toxicities persist (see section 4.4). 

Recommended dose modifications for toxicities in patients treated with docetaxel in combination with 

cisplatin and 5-fluorouracil (5-FU): 

 

 

 



141 

Toxicity Dose adjustment 

Diarrhoea grade 3  First episode: reduce 5-FU dose by 20%. 

Second episode: then reduce docetaxel dose by 20%. 

Diarrhoea grade 4 First episode: reduce docetaxel and 5-FU doses by 20%. 

Second episode: discontinue treatment. 

Stomatitis/mucositis grade 3  First episode: reduce 5-FU dose by 20%. 

Second episode: stop 5-FU only, at all subsequent cycles. 

Third episode: reduce docetaxel dose by 20%. 

Stomatitis/mucositis grade 4 First episode: stop 5-FU only, at all subsequent cycles. 

Second episode: reduce docetaxel dose by 20%. 

 

For cisplatin and 5-fluorouracil dose adjustments, see the corresponding summary of product 

characteristics. 

 

In the pivotal SCCHN studies patients who experienced complicated neutropenia (including prolonged 

neutropenia, febrile neutropenia, or infection), it was recommended to use G-CSF to provide 

prophylactic coverage (eg, day 6-15) in all subsequent cycles. 

 

Special populations 

 

Patients with hepatic impairment 

Based on pharmacokinetic data with docetaxel at 100 mg/m² as single agent, patients who have both 

elevations of transaminase (ALT and/or AST) greater than 1.5 times the upper limit of the normal 

range (ULN) and alkaline phosphatase greater than 2.5 times the ULN, the recommended dose of 

docetaxel is 75 mg/m2 (see sections 4.4 and 5.2). For those patients with serum bilirubin > ULN and/or 

ALT and AST > 3.5 times the ULN associated with alkaline phosphatase > 6 times the ULN, no 

dose-reduction can be recommended and docetaxel should not be used unless strictly indicated. 

In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric 

adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST > 1.5 × ULN 

associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no 

dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No 

data are available in patients with hepatic impairment treated by docetaxel in combination in the other 

indications.  

 

Paediatric population 

The safety and efficacy of DOCETAXEL KABI in nasopharyngeal carcinoma in children aged 

1 month to less than 18 years have not yet been established. 

There is no relevant use of DOCETAXEL KABI in the paediatric population in the indications breast 

cancer, non-small cell lung cancer, prostate cancer, gastric carcinoma and head and neck cancer, not 

including type II and III less differentiated nasopharyngeal carcinoma. 

 

Elderly 

Based on a population pharmacokinetic analysis, there are no special instructions for use in the elderly. 

In combination with capecitabine, for patients 60 years of age or more, a starting dose reduction of 

capecitabine to 75% is recommended (see capecitabine summary of product characteristics). 

 

Method of administration 

For instructions on preparation and administration of the product, see section 6.6. 

 

4.3 Contraindications 

 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 

Patients with baseline neutrophil count of < 1,500 cells/mm3. 



142 

Patients with severe liver impairment (see sections 4.2 and 4.4). 

 

Contraindications for other medicinal products also apply, when combined with docetaxel. 

 

 

4.4 Special warnings and precautions for use 

 

For breast and non-small cell lung cancers, premedication consisting of an oral corticosteroid, such as 

dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to docetaxel 

administration, unless contraindicated, can reduce the incidence and severity of fluid retention as well 

as the severity of hypersensitivity reactions. For prostate cancer, the premedication is oral 

dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the docetaxel infusion (see section 4.2). 

 

Haematology 

 

Neutropenia is the most frequent adverse reaction of docetaxel. Neutrophil nadirs occurred at a median 

of 7 days but this interval may be shorter in heavily pre-treated patients. Frequent monitoring of 

complete blood counts should be conducted on all patients receiving docetaxel. Patients should be 

retreated with docetaxel when neutrophils recover to a level ≥ 1,500 cells/mm3 (see section 4.2). 

 

In the case of severe neutropenia (< 500 cells/mm3 for seven days or more) during a course of 

docetaxel therapy, a reduction in dose for subsequent courses of therapy or the use of appropriate 

symptomatic measures are recommended (see section 4.2). 

 

In patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (TCF), febrile 

neutropenia and neutropenic infection occurred at lower rates when patients received prophylactic 

G-CSF. Patients treated with TCF should receive prophylactic G-CSF to mitigate the risk of 

complicated neutropenia (febrile neutropenia, prolonged neutropenia or neutropenic infection). 

Patients receiving TCF should be closely monitored (see sections 4.2 and 4.8). 

 

In patients treated with docetaxel in combination with doxorubicin and cyclophosphamide (TAC), 

febrile neutropenia and/or neutropenic infection occurred at lower rates when patients received 

primary G-CSF prophylaxis. Primary G-CSF prophylaxis should be considered in patients who receive 

adjuvant therapy with TAC for breast cancer to mitigate the risk of complicated neutropenia (febrile 

neutropenia, prolonged neutropenia or neutropenic infection). Patients receiving TAC should be 

closely monitored (see sections 4.2 and 4.8). 

 

Gastrointestinal reactions 

 

Caution is recommended for patients with neutropenia, particularly at risk for developing 

gastrointestinal complications. Although majority of cases occurred during the first or second cycle of 

docetaxel containing regimen, enterocolitis could develop at any time, and could lead to death as early 

as on the first day of onset. Patients should be closely monitored for early manifestations of serious 

gastrointestinal toxicity (see sections 4.2, 4.4 Haematology, and 4.8). 

 

Hypersensitivity reactions 

 

Patients should be observed closely for hypersensitivity reactions especially during the first and 

second infusions. Hypersensitivity reactions may occur within a few minutes following the initiation 

of the infusion of docetaxel, thus facilities for the treatment of hypotension and bronchospasm should 

be available. If hypersensitivity reactions occur, minor symptoms such as flushing or localised 

cutaneous reactions do not require interruption of therapy. However, severe reactions, such as severe 

hypotension, bronchospasm or generalised rash/erythema require immediate discontinuation of 

docetaxel and appropriate therapy. Patients who have developed severe hypersensitivity reactions 

should not be re-challenged with docetaxel. Patients who have previously experienced a 

hypersensitivity reaction to paclitaxel may be at risk to develop hypersensitivity reaction to docetaxel, 



143 

including more severe hypersensitivity reaction. These patients should be closely monitored during 

initiation of docetaxel therapy. 

 

Cutaneous reactions 

 

Localised skin erythema of the extremities (palms of the hands and soles of the feet) with oedema 

followed by desquamation has been observed. Severe symptoms such as eruptions followed by 

desquamation which lead to interruption or discontinuation of docetaxel treatment were reported (see 

section 4.2). 

 

Severe Cutaneous Adverse Reactions (SCARs) such as Stevens-Johnson Syndrome (SJS), Toxic 

Epidermal Necrolysis (TEN) and Acute Generalized Exanthematous Pustulosis (AGEP) have been 

reported with docetaxel treatment. Patients should be informed about the signs and symptoms of 

serious skin manifestations and closely monitored. If signs and symptoms suggestive of these reactions 

appear discontinuation of docetaxel should be considered. 

 

Fluid retention 

 

Patients with severe fluid retention such as pleural effusion, pericardial effusion and ascites should be 

monitored closely. 

 

Respiratory disorders 

 

Acute respiratory distress syndrome, interstitial pneumonia/pneumonitis, interstitial lung disease, 

pulmonary fibrosis and respiratory failure have been reported and may be associated with fatal 

outcome. Cases of radiation pneumonitis have been reported in patients receiving concomitant 

radiotherapy. 

 

If new or worsening pulmonary symptoms develop, patients should be closely monitored, promptly 

investigated, and appropriately treated. Interruption of docetaxel therapy is recommended until 

diagnosis is available. Early use of supportive care measures may help improve the condition. The 

benefit of resuming docetaxel treatment must be carefully evaluated. 

 

Patients with liver impairment 

 

In patients treated with docetaxel at 100 mg/m2 as single agent who have serum transaminase levels 

(ALT and/or AST) greater than 1.5 times the ULN concurrent with serum alkaline phosphatase levels 

greater than 2.5 times the ULN, there is a higher risk of developing severe adverse reactions such as 

toxic deaths including sepsis and gastrointestinal haemorrhage which can be fatal, febrile neutropenia, 

infections, thrombocytopenia, stomatitis and asthenia. Therefore, the recommended dose of docetaxel 

in those patients with elevated liver function test (LFTs) is 75 mg/m2 and LFTs should be measured at 

baseline and before each cycle (see section 4.2). 

For patients with serum bilirubin levels > ULN and/or ALT and AST > 3.5 times the ULN concurrent 

with serum alkaline phosphatase levels > 6 times the ULN, no dose-reduction can be recommended 

and docetaxel should not be used unless strictly indicated. 

In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric 

adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST > 1.5 × ULN 

associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no 

dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No 

data are available in patients with hepatic impairment treated by docetaxel in combination in the other 

indications.  

 

Patients with renal impairment 

 

There are no data available in patients with severely impaired renal function treated with docetaxel. 

 

 



144 

Nervous system 

The development of severe peripheral neurotoxicity requires a reduction of dose (see section 4.2). 

 

Cardiac toxicity 

 

Heart failure has been observed in patients receiving docetaxel in combination with trastuzumab, 

particularly following anthracycline (doxorubicin or epirubicin)-containing chemotherapy. This may 

be moderate to severe and has been associated with death (see section 4.8). 

 

When patients are candidates for treatment with docetaxel in combination with trastuzumab, they 

should undergo baseline cardiac assessment. Cardiac function should be further monitored during 

treatment (e.g. every three months) to help identify patients who may develop cardiac dysfunction. For 

more details see summary of product characteristics of trastuzumab.  

 

Ventricular arrhythmia including ventricular tachycardia (sometimes fatal) has been reported in 

patients treated with docetaxel in combination regimens including doxorubicin, 5-fluorouracil and/ or 

cyclophosphamide (see section 4.8).  

Baseline cardiac assessment is recommended.   

 

Eye disorders 
 

Cystoid macular oedema (CMO) has been reported in patients treated with docetaxel. Patients with 

impaired vision should undergo a prompt and complete ophthalmologic examination. In case CMO is 

diagnosed, docetaxel treatment should be discontinued and appropriate treatment initiated (see section 

4.8). 

 

Second primary malignancies 

 

Second primary malignancies have been reported when docetaxel was given in combination with 

anticancer treatments known to be associated with second primary malignancies.  Second primary 

malignancies (including acute myeloid leukemia, myelodysplastic syndrome and non-Hodgkin 

lymphoma) may occur several months or years after docetaxel-containing therapy. Patients should be 

monitored for second primary malignancies (see section 4.8). 

 

Others 

 

Contraceptive measures must be taken by both men and women during treatment and for men at least 

6 months after cessation of therapy (see section 4.6). 

 

The concomitant use of docetaxel with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, 

clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and 

voriconazole) should be avoided (see section 4.5). 

 

Additional cautions for use in adjuvant treatment of breast cancer 

 

Complicated neutropenia 

For patients who experience complicated neutropenia (prolonged neutropenia, febrile neutropenia or 

infection), G-CSF and dose reduction should be considered (see section 4.2). 

 

Gastrointestinal reactions 

Symptoms such as early abdominal pain and tenderness, fever, diarrhoea, with or without neutropenia, 

may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated 

promptly. 

 

 

 

 



145 

Congestive heart failure (CHF) 

Patients should be monitored for symptoms of congestive heart failure during therapy and during the 

follow up period. In patients treated with the TAC regimen for node positive breast cancer, the risk of 

CHF has been shown to be higher during the first year after treatment (see sections 4.8 and 5.1). 

 

Patients with 4+ nodes 

As the benefit observed in patient with 4+ nodes was not statistically significant on disease-free 

survival (DFS) and overall survival (OS), the positive benefit/risk ratio for TAC in patients with 4+ 

nodes was not fully demonstrated at the final analysis (see section 5.1). 

 

Elderly  

Cautions for use in adjuvant treatment of breast cancer 

There are limited data available in patients > 70 years of age on docetaxel use in combination with 

doxorubicin and cyclophosphamide. 

 

Cautions for use in castration-resistant prostate cancer 

Of the 333 patients treated with docetaxel every three weeks in a prostate cancer study, 209 patients 

were 65 years of age or greater and 68 patients were older than 75 years. In patients treated with 

docetaxel every three weeks, the incidence of related nail changes occurred at a rate ≥ 10% higher in 

patients who were 65 years of age or greater compared to younger patients. The incidence of related 

fever, diarrhoea, anorexia, and peripheral oedema occurred at rates ≥ 10% higher in patients who were 

75 years of age or greater versus less than 65 years. 

 

Cautions for use in hormone-sensitive prostate cancer 

Of the 545 patients treated with docetaxel every 3 weeks in a hormone-sensitive prostate cancer study 

(STAMPEDE), 296 patients were 65 years of age or older, and 48 patients were 75 years of age or 

older. More patients aged ≥65 years in the docetaxel arm reported hypersensitivity reaction, 

neutropenia, anaemia, fluid retention, dyspnea, and nail changes when compared to the patients aged 

less than 65 years. None of these increases in frequency reached 10% difference with the control arm. 

In patients who were 75 years of age or older, when compared to younger patients, neutropenia, 

anaemia, diarrhea, dyspnea and upper respiratory tract infection were reported with a greater incidence 

(at least 10% higher).  

 

Cautions for use in gastric adenocarcinoma cancer 

Among the 300 (221 patients in the phase III part of the study and 79 patients in the phase II part) 

patients treated with docetaxel in combination with cisplatin and 5-fluorouracil in the gastric cancer 

study, 74 were 65 years of age or older and 4 patients were 75 years of age or older. The incidence of 

serious adverse events was higher in older people compared to younger patients. The incidence of the 

following adverse events (all grades): lethargy, stomatitis, neutropenic infection occurred at rates 

≥ 10% higher in patients who were 65 years of age or older compared to younger patients. 

Elderly treated with TCF should be closely monitored. 

 
Excipients 

 
This medicinal product contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 3.16 g ethanol 

anhydrous per vial, equivalent to 80 ml of beer or 32 ml wine. 

Harmful for those suffering from alcoholism. 

To be taken into account in pregnant or breast-feeding women, children and high-risk groups 

such as patients with liver disease, or epilepsy. 
 

Consideration should be given to possible effects on the central nervous system. 

 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

The amount of alcohol in this medicinal product may alter the effects of other medicinal products. 



146 

 

In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant 

administration of compounds which induce, inhibit or are metabolised by (and thus may inhibit the 

enzyme competitively) cytochrome P450-3A such as ciclosporine, ketoconazole and erythromycin. As 

a result, caution should be exercised when treating patients with these medicinal products as 

concomitant therapy since there is a potential for a significant interaction. 

In case of combination with CYP3A4 inhibitors, the occurrence of docetaxel adverse reactions may 

increase, as a result of reduced metabolism. If the concomitant use of a strong CYP3A4 inhibitor (e.g., 

ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, 

telithromycin and voriconazole) cannot be avoided, a close clinical surveillance is warranted and a 

dose-adjustment of docetaxel may be suitable during the treatment with the strong CYP3A4 inhibitor 

(see section 4.4). In a pharmacokinetic study with 7 patients, the co-administration of docetaxel with 

the strong CYP3A4 inhibitor ketoconazole leads to a significant decrease in docetaxel clearance by 

49%. 

Docetaxel pharmacokinetics in the presence of prednisone was studied in patients with metastatic 

prostate cancer. Docetaxel is metabolised by CYP3A4 and prednisone is known to induce CYP3A4. 

No statistically significant effect of prednisone on the pharmacokinetics of docetaxel was observed. 

 

Docetaxel is highly protein bound (> 95%). Although the possible in vivo interaction of docetaxel with 

concomitantly administered medicinal product has not been investigated formally, in vitro interactions 

with tightly protein-bound agents such as erythromycin, diphenhydramine, propranolol, propafenone, 

phenytoin, salicylate, sulfamethoxazole and sodium valproate did not affect protein binding of 

docetaxel. In addition, dexamethasone did not affect protein binding of docetaxel. Docetaxel did not 

influence the binding of digitoxin. 

 

The pharmacokinetics of docetaxel, doxorubicin and cyclophosphamide were not influenced by their 

co-administration. Limited data from a single uncontrolled study were suggestive of an interaction 

between docetaxel and carboplatin. When combined to docetaxel, the clearance of carboplatin was 

about 50% higher than values previously reported for carboplatin monotherapy. 

 

 

4.6 Fertility, pregnancy and lactation 

 

Women of childbearing potential/ Contraception in males and females 

 

Women of childbearing age receiving docetaxel should be advised to avoid becoming pregnant, and to 

inform the treating physician immediately should this occur. An effective method of contraception 

should be used during treatment. 

 

Pregnancy 

 

There is no information on the use of docetaxel in pregnant women. Docetaxel has been shown to be 

both embryotoxic and foetotoxic in rabbits and rats, and to reduce fertility in rats (see section 5.3). As 

with other cytotoxic medicinal products, docetaxel may cause foetal harm when administered to 

pregnant women. Therefore, docetaxel must not be used during pregnancy unless clearly indicated.  

 

Breast-feeding 

 

Docetaxel is a lipophilic substance but it is not known whether it is excreted in human milk. 

Consequently, because of the potential for adverse reactions in nursing infants, breast feeding must be 

discontinued for the duration of docetaxel therapy. 

 

 

 



147 

 

 

Fertility 

 

In non clinical studies, docetaxel has genotoxic effects and may alter male fertility (see section 5.3). 

Therefore, men being treated with docetaxel are advised not to father a child during and up to 

6 months after treatment and to seek advice on conservation of sperm prior to treatment. 

 

 

4.7 Effects on ability to drive and use machines 

 

No studies on the effects on the ability to drive and use machines have been performed. The amount of 

alcohol in this medicinal product and the side effects of the product may impair the ability to drive or 

use machines (see sections 4.4 and 4.8). Therefore, patients should be warned of the potential impact 

of the amount of alcohol and the side effects of this medicinal product on the ability to drive or use 

machines, and be advised not to drive or use machines if they experience these side effects during 

treatment. 

 

 

4.8 Undesirable effects 

 

Summary of the safety profile for all indications 

 

The adverse reactions considered to be possibly or probably related to the administration of docetaxel 

have been obtained in: 

• 1,312 and 121 patients who received 100 mg/m² and 75 mg/m² of docetaxel as a single agent 
respectively. 

• 258 patients who received docetaxel in combination with doxorubicin. 

• 406 patients who received docetaxel in combination with cisplatin. 

• 92 patients treated with docetaxel in combination with trastuzumab. 

• 255 patients who received docetaxel in combination with capecitabine. 

• 332 patients (TAX327) who received docetaxel in combination with prednisone or prednisolone 
(clinically important treatment related adverse events are presented). 

• 1,276 patients (744 and 532 in TAX 316 and GEICAM 9805 respectively) who received 
docetaxel in combination with doxorubicin and cyclophosphamide (clinically important 

treatment related adverse events are presented). 

• 300 gastric adenocarcinoma patients (221 patients in the phase III part of the study and 
79 patients in the phase II part) who received docetaxel in combination with cisplatin and 

5-fluorouracil (clinically important treatment related adverse events are presented). 

• 174 and 251 head and neck cancer patients who received docetaxel in combination with 
cisplatin and 5-fluorouracil (clinically important treatment related adverse events are presented). 

• 545 patients (STAMPEDE study) who received docetaxel in combination with prednisone or 
prednisolone and ADT. 

 

These reactions were described using the NCI Common Toxicity Criteria (grade 3 = G3; 

grade 3-4 = G3/4; grade 4 = G4), the COSTART and the MedDRA terms. Frequencies are defined as: 
very common (≥ 1/10), common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare 

(≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from available 

data). 

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 

 

The most commonly reported adverse reactions of docetaxel alone are: neutropenia (which was 

reversible and not cumulative; the median day to nadir was 7 days and the median duration of severe 

neutropenia (< 500 cells/mm3) was 7 days), anaemia, alopecia, nausea, vomiting, stomatitis, diarrhoea 



148 

and asthenia. The severity of adverse events of docetaxel may be increased when docetaxel is given in 

combination with other chemotherapeutic agents. 

For combination with trastuzumab, adverse events (all grades) reported in ≥ 10% are displayed. There 

was an increased incidence of SAEs (40% vs. 31%) and Grade 4 AEs (34% vs. 23%) in the 

trastuzumab combination arm compared to docetaxel monotherapy. 

 

For combination with capecitabine, the most frequent treatment-related undesirable effects (≥ 5%) 

reported in a phase III study in breast cancer patients failing anthracycline treatment are presented (see 

capecitabine summary of product characteristics). 

 

For combination with ADT and with prednisone or prednisolone (STAMPEDE study), adverse events 

occurring occurring over the 6 cycles of treatment with docetaxel and having at least 2% higher 

incidence in the docetaxel treatment arm by comparison to the control arm, are presented, using the 

CTCAE grading scale. 

 

The following adverse reactions are frequently observed with docetaxel:  

 

Immune system disorders 

 

Hypersensitivity reactions have generally occurred within a few minutes following the start of the 

infusion of docetaxel and were usually mild to moderate. The most frequently reported symptoms 

were flushing, rash with or without pruritus, chest tightness, back pain, dyspnoea and fever or chills. 

Severe reactions were characterised by hypotension and/or bronchospasm or generalized 

rash/erythema (see section 4.4). 

 

Nervous system disorders 

 

The development of severe peripheral neurotoxicity requires a reduction of dose (see sections 4.2 and 

4.4). Mild to moderate neuro-sensory signs are characterised by paraesthesia, dysesthesia or pain 

including burning. Neuro-motor events are mainly characterised by weakness. 

 

Skin and subcutaneous tissue disorders 

 

Reversible cutaneous reactions have been observed and were generally considered as mild to 

moderate. Reactions were characterised by a rash including localised eruptions mainly on the feet and 

hands (including severe hand and foot syndrome), but also on the arms, face or thorax, and frequently 

associated with pruritus. Eruptions generally occurred within one week after the docetaxel infusion. 

Less frequently, severe symptoms such as eruptions followed by desquamation which rarely lead to 

interruption or discontinuation of docetaxel treatment were reported (see sections 4.2 and 4.4). Severe 

nail disorders are characterised by hypo- or hyperpigmentation and sometimes pain and onycholysis. 

 

General disorders and administration site conditions 

 

Infusion site reactions were generally mild and consisted of hyper pigmentation, inflammation, 

redness or dryness of the skin, phlebitis or extravasation and swelling of the vein.  

Fluid retention includes events such as peripheral oedema and less frequently pleural effusion, 

pericardial effusion, ascites and weight gain. The peripheral oedema usually starts at the lower 

extremities and may become generalised with a weight gain of 3 kg or more. Fluid retention is 

cumulative in incidence and severity (see section 4.4). 

 

Tabulated list of adverse reactions in breast cancer for DOCETAXEL KABI 100 mg/m² single agent 

 

MedDRA system 

organ classes 

Very common 

adverse reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infections 

(G3/4: 5.7%; including 

Infection associated 

with G4 neutropenia 

  



149 

MedDRA system 

organ classes 

Very common 

adverse reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

sepsis and pneumonia, 

fatal in 1.7%) 

(G3/4: 4.6%) 

Blood and lymphatic 

system disorders 

Neutropenia 

(G4: 76.4%); 

Anaemia 

(G3/4: 8.9%); 

Febrile neutropenia 

Thrombocytopenia 

(G4: 0.2%) 

  

Immune system 

disorders 

Hypersensitivity 

(G3/4: 5.3%) 

    

Metabolism and 

nutrition disorders 

Anorexia     

Nervous system 

disorders 

Peripheral sensory 

neuropathy 

(G3: 4.1%); 

Peripheral motor 

neuropathy 

(G3/4: 4%); 

Dysgeusia 

(severe: 0.07%) 

    

Cardiac disorders   Arrhythmia 

(G3/4: 0.7%) 

Cardiac failure 

Vascular disorders   Hypotension; 

Hypertension; 

Haemorrhage 

  

Respiratory, thoracic 

and mediastinal 

disorders 

Dyspnoea 

(severe: 2.7%) 

    

Gastrointestinal 

disorders 

Stomatitis 

(G3/4: 5.3%); 

Diarrhoea (G3/4: 4%); 

Nausea (G3/4: 4%); 

Vomiting (G3/4: 3%) 

Constipation 

(severe: 0.2%); 

Abdominal pain 

(severe: 1%); 

Gastrointestinal 

haemorrhage 

(severe: 0.3%) 

Oesophagitis 

(severe: 0.4%) 

Skin and subcutaneous 

tissue disorders 

Alopecia; 

Skin reaction 

(G3/4: 5.9%); 

Nail disorders 

(severe: 2.6%) 

    

Musculoskeletal and 

connective tissue 

disorders 

Myalgia 

(severe: 1.4%) 

Arthralgia   

General disorders and 

administration site 

conditions 

Fluid retention 

(severe: 6.5%); 

Asthenia 

(severe: 11.2%); 

Pain 

Infusion site reaction;  

Non-cardiac chest pain 

(severe: 0.4%) 

  



150 

MedDRA system 

organ classes 

Very common 

adverse reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Investigations   G3/4 Blood bilirubin 

increased (< 5%); 

G3/4 Blood alkaline 

phosphatase increased 

(< 4%);G3/4 AST 

increased (< 3%); 

G3/4 ALT increased 

(< 2%) 

  

 

Description of selected adverse reactions in breast cancer for DOCETAXEL KABI 100 mg/m² single 

agent 

 

Blood and lymphatic system disorders 

Rare: bleeding episodes associated with grade 3/4 thrombocytopenia.  

 

Nervous system disorders 

Reversibility data are available among 35.3% of patients who developed neurotoxicity following 

docetaxel treatment at 100 mg/m² as single agent. The events were spontaneously reversible within 

3 months. 

 

Skin and subcutaneous tissue disorders 

Very rare: one case of alopecia non-reversible at the end of the study. 73% of the cutaneous reactions 

were reversible within 21 days. 

 

General disorders and administration site conditions 

The median cumulative dose to treatment discontinuation was more than 1,000 mg/m2 and the median 

time to fluid retention reversibility was 16.4 weeks (range 0 to 42 weeks). The onset of moderate and 

severe retention is delayed (median cumulative dose: 818.9 mg/m2) in patients with premedication 

compared with patients without premedication (median cumulative dose: 489.7 mg/m2); however, it 

has been reported in some patients during the early courses of therapy. 

 

Tabulated list of adverse reactions in non-small cell lungcancer for DOCETAXEL KABI 75 mg/m² 

single agent 

 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Infections and infestations Infections (G3/4: 5%)   

Blood and lymphatic system 

disorders 

Neutropenia (G4: 54.2%); 

Anaemia (G3/4: 10.8%); 

Thrombocytopenia (G4: 1.7%) 

Febrile neutropenia 

Immune system disorders   Hypersensitivity (no severe) 

Metabolism and nutrition 

disorders 

Anorexia   

Nervous system disorders Peripheral sensory neuropathy 

(G3/4: 0.8%) 

Peripheral motor neuropathy 

(G3/4: 2.5%) 

Cardiac disorders   Arrhythmia (no severe) 

Vascular disorders   Hypotension 

Gastrointestinal disorders Nausea (G3/4: 3.3%); 

Stomatitis (G3/4: 1.7%); 

Constipation 



151 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Vomiting (G3/4: 0.8%); 

Diarrhoea (G3/4: 1.7%) 

Skin and subcutaneous tissue 

disorders 

Alopecia; 

Skin reaction (G3/4: 0.8%) 

Nail disorders (severe: 0.8%) 

Musculoskeletal and 

connective tissue disorders 

  Myalgia 

General disorders and 

administration site conditions 

Asthenia (severe: 12.4%); 

Fluid retention 

(severe: 0.8%);Pain 

  

Investigations   G3/4 Blood bilirubin 

increased (< 2%) 

 

Tabulated list of adverse reactions in breast cancer for DOCETAXEL KABI 75 mg/m² in combination 

with doxorubicin 

 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 7.8%)     

Blood and lymphatic 

system disorders 

Neutropenia 

(G4: 91.7%); 

Anaemia (G3/4: 9.4%); 

Febrile neutropenia; 

Thrombocytopenia 

(G4: 0.8%) 

    

Immune system 

disorders 

  Hypersensitivity 

(G3/4: 1.2%) 

  

Metabolism and 

nutrition disorders 

  Anorexia   

Nervous system 

disorders 

Peripheral sensory 

neuropathy (G3: 0.4%) 

Peripheral motor 

neuropathy 

(G3/4: 0.4%) 

  

Cardiac disorders   Cardiac failure; 

Arrhythmia (no 

severe) 

  

Vascular disorders     Hypotension 

Gastrointestinal 

disorders 

Nausea (G3/4: 5%); 

Stomatitis 

(G3/4: 7.8%); 

Diarrhoea 

(G3/4: 6.2%); 

Vomiting (G3/4: 5%); 

Constipation 

    

Skin and subcutaneous 

tissue disorders 

Alopecia; 

Nail disorders 

(severe: 0.4%); 

    



152 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Skin reaction (no 

severe) 

Musculoskeletal and 

connective tissue 

disorders 

  Myalgia   

General disorders and 

administration site 

conditions 

Asthenia 

(severe: 8.1%); 

Fluid retention 

(severe: 1.2%); 

Pain 

Infusion site reaction   

Investigations   G3/4 Blood bilirubin 

increased (< 2.5%); 

G3/4 Blood alkaline 

phosphatase increased 

(< 2.5%) 

G3/4 AST increased 

(< 1%); 

G3/4 ALT increased 

(< 1%) 

 

Tabulated list of adverse reactions in non-small cell lung cancer for DOCETAXEL KABI 75 mg/m² in 

combination with cisplatin 

 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 5.7%)     

Blood and 

lymphatic system 

disorders 

Neutropenia (G4: 51.5%); 

Anaemia (G3/4: 6.9%); 

Thrombocytopenia 

(G4: 0.5%) 

Febrile neutropenia   

Immune system 

disorders 

Hypersensitivity 

(G3/4: 2.5%) 

    

Metabolism and 

nutrition disorders 

Anorexia     

Nervous system 

disorders 

Peripheral sensory 

neuropathy (G3: 3.7%); 

Peripheral motor 

neuropathy (G3/4: 2%) 

    

Cardiac disorders   Arrhythmia 

(G3/4: 0.7%) 

Cardiac failure 

Vascular disorders   Hypotension 

(G3/4: 0.7%) 

  

Gastrointestinal 

disorders 

Nausea (G3/4: 9.6%); 

Vomiting (G3/4: 7.6%); 

Diarrhoea (G3/4: 6.4%); 

Stomatitis (G3/4: 2%) 

Constipation   

Skin and 

subcutaneous 

tissue disorders 

Alopecia; 

Nail disorders 

(severe: 0.7%); 

Skin reaction (G3/4: 0.2%) 

    



153 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Musculoskeletal 

and connective 

tissue disorders 

Myalgia (severe: 0.5%)     

General disorders 

and administration 

site conditions 

Asthenia (severe: 9.9%); 

Fluid retention 

(severe: 0.7%); 

Fever (G3/4: 1.2%) 

Infusion site reaction; 

Pain 

  

Investigations   G3/4 Blood bilirubin 

increased (2.1%); G3/4 

ALT increased (1.3%) 

G3/4 AST increased 

(0.5%); G3/4 Blood 

alkaline phosphatase 

increased (0.3%) 

Tabulated list of adverse reactions in breast cancer for DOCETAXEL KABI 100 mg/m² in 

combination with trastuzumab 

 

MedDRA system 

organ classes 

Very common adverse reactions Common adverse reactions 

 

Blood and lymphatic 

system disorders 

Neutropenia (G3/4: 32%); 

Febrile neutropenia (includes 

neutropenia associated with fever and 

antibiotic use) or neutropenic sepsis  

  

Metabolism and 

nutrition disorders 

Anorexia   

Psychiatric disorders Insomnia   

Nervous system 

disorders 

Paraesthesia; Headache; Dysgeusia; 

Hypoaesthesia 

  

Eye disorders Lacrimation increased; Conjunctivitis   

Cardiac disorders   Cardiac failure 

Vascular disorders Lymphoedema   

Respiratory, thoracic 

and mediastinal 

disorders 

Epistaxis; Pharyngolaryngeal pain; 

Nasopharyngitis; Dyspnoea; 

Cough; Rhinorrhoea 

  

Gastrointestinal 

disorders 

Nausea; Diarrhoea; Vomiting; 

Constipation; Stomatitis; Dyspepsia; 

Abdominal pain 

  

Skin and 

subcutaneous tissue 

disorders 

Alopecia; Erythema; Rash; Nail 

disorders 

  

Musculoskeletal and 

connective tissue 

disorders 

Myalgia; Arthralgia; Pain in 

extremity; Bone pain; Back pain 

  

General disorders 

and administration 

site conditions 

Asthenia; Oedema peripheral; 

Pyrexia; Fatigue; Mucosal 

inflammation; Pain; Influenza like 

illness; Chest pain; Chills 

Lethargy 

Investigations Weight increased   



154 

Description of selected adverse reactions in breast cancer for DOCETAXEL KABI 100 mg/m² in 

combination with trastuzumab 

 

Blood and lymphatic system disorders 

Very common: Haematological toxicity was increased in patients receiving trastuzumab and 

docetaxel, compared with docetaxel alone (32% grade 3/4 neutropenia versus 22%, using NCI-CTC 

criteria). Note that this is likely to be an underestimate since docetaxel alone at a dose of 100 mg/m2 is 

known to result in neutropenia in 97% of patients, 76% grade 4, based on nadir blood counts. The 

incidence of febrile neutropenia/neutropenic sepsis was also increased in patients treated with 

Herceptin plus docetaxel (23% versus 17% for patients treated with docetaxel alone). 

 

Cardiac disorders 

Symptomatic cardiac failure was reported in 2.2% of the patients who received docetaxel plus 

trastuzumab compared to 0% of patients given docetaxel alone. In the docetaxel plus trastuzumab arm, 

64% had received a prior anthracycline as adjuvant therapy compared with 55% in the docetaxel arm 

alone. 

 

Tabulated list of adverse reactions in breast cancer for DOCETAXEL KABI 75 mg/m² in combination 

with capecitabine 

 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Infections and infestations   Oral candidiasis (G3/4: < 1%) 

Blood and lymphatic system 

disorders 

Neutropenia (G3/4: 63%); 

Anaemia (G3/4: 10%) 

Thrombocytopenia (G3/4: 3%) 

Metabolism and nutrition 

disorders 

Anorexia (G3/4: 1%); 

Decreased appetite 

Dehydration (G3/4: 2%) 

Nervous system disorders Dysgeusia (G3/4: < 1%); 

Paraesthesia (G3/4: < 1%) 

 

Dizziness; 

Headache (G3/4: < 1%); 

Neuropathy peripheral 

Eye disorders Lacrimation increased   

Respiratory, thoracic and 

mediastinal disorders 

Pharyngolaryngeal pain 

(G3/4: 2%) 

Dyspnoea (G3/4: 1%); 

Cough (G3/4: < 1%); 

Epistaxis (G3/4: < 1%) 

Gastrointestinal disorders Stomatitis (G3/4: 18%); 

Diarrhoea (G3/4: 14%); 

Nausea (G3/4: 6%); 

Vomiting (G3/4: 4%); 

Constipation (G3/4: 1%); 

Abdominal pain (G3/4: 2%); 

Dyspepsia 

Abdominal pain upper; 

Dry mouth 

Skin and subcutaneous tissue 

disorders 

Hand-foot syndrome 

(G3/4: 24%); 

Alopecia (G3/4: 6%); 

Nail disorders (G3/4: 2%) 

Dermatitis; 

Rash erythematous 

(G3/4: < 1%); 

Nail discolouration; 

Onycholysis (G3/4: 1%) 

Musculoskeletal and 

connective tissue disorders 

Myalgia (G3/4: 2%); 

Arthralgia (G3/4: 1%) 

Pain in extremity (G3/4: < 1%); 

Back pain (G3/4: 1%) 

General disorders and 

administration site conditions 

Asthenia (G3/4: 3%); 

Pyrexia (G3/4: 1%); 

Fatigue/weakness (G3/4: 5%); 

Lethargy; 

Pain 



155 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Oedema peripheral (G3/4: 1%) 

Investigations   Weight decreased; 

G3/4 Blood bilirubin increased 

(9%) 

 

Tabulated list of adverse reactions in metastatic castration-resistant prostate cancer for DOCETAXEL 

KABI 75 mg/m² in combination with prednisone or prednisolone 

 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Infections and infestations Infection (G3/4: 3.3%)   

Blood and lymphatic system 

disorders 

Neutropenia (G3/4: 32%); 

Anaemia (G3/4: 4.9%) 

Thrombocytopenia 

(G3/4: 0.6%); 

Febrile neutropenia 

Immune system disorders   Hypersensitivity (G3/4: 0.6%) 

Metabolism and nutrition 

disorders 

Anorexia (G3/4: 0.6%)   

Nervous system disorders Peripheral sensory neuropathy 

(G3/4: 1.2%); 

Dysgeusia (G3/4: 0%) 

Peripheral motor neuropathy 

(G3/4: 0%) 

Eye disorders   Lacrimation increased 

(G3/4: 0.6%) 

Cardiac disorders   Cardiac left ventricular 

function decrease (G3/4: 0.3%) 

Respiratory, thoracic and 

mediastinal disorders 

  Epistaxis (G3/4: 0%); 

Dyspnoea (G3/4: 0.6%); 

Cough (G3/4: 0%) 

Gastrointestinal disorders Nausea (G3/4: 2.4%); 

Diarrhoea (G3/4: 1.2%); 

Stomatitis/Pharyngitis 

(G3/4: 0.9%); 

Vomiting (G3/4: 1.2%) 

  

Skin and subcutaneous tissue 

disorders 

Alopecia; 

Nail disorders (no severe) 

Exfoliative rash (G3/4: 0.3%) 

Musculoskeletal and 

connective bone disorders 

  Arthralgia (G3/4: 0.3%); 

Myalgia (G3/4: 0.3%) 

General disorders and 

administration site conditions 

Fatigue (G3/4: 3.9%); 

Fluid retention (severe: 0.6%) 

  

 



156 

Tabulated list of adverse reactions in high-risk locally advanced or metastatic hormone-sensitive 

prostate cancer for DOCETAXEL KABI 75 mg/m² in combination with prednisone or prednisolone 

and ADT (STAMPEDE study)  

 

MedDRA system organ 

classes 

 

Very common adverse 

reactions 

Common adverse reactions 

Blood and lymphatic system 

disorders 

Neutropenia (G3-4: 12 %) 

Anaemia  

Febrile neutropenia (G3-4: 15%) 

 

Immune system disorders   Hypersensitivity (G3-4: 1%) 

Endocrine disorders  Diabetes (G3-4: 1%) 

Metabolism and nutrition 

disorders 

 Anorexia  

Psychiatric disorders Insomnia (G3: 1%)  

Nervous system disorders Peripheral sensory neuropathy 

(≥G3: 2%)a 

Headache 

 

Dizziness 

Eye disorders  Blurred vision 

Cardiac disorders  Hypotension (G3: 0%) 

 

Respiratory, thoracic and 

mediastinal disorders  

Dyspnea (G3: 1%) 

Coughing (G3: 0%) 

Upper respiratory tract infection 

(G3: 1%)  

Pharyngitis (G3: 0%) 

 

 

Gastrointestinal disorders  Diarrhea (G3: 3%) 

Stomatitis (G3: 0%) 

Constipation (G3: 0%) 

Nausea (G3: 1%) 

Dyspepsia 

Abdominal pain (G3: 0%) 

Flatulence 

Vomiting (G3: 1%) 

 

Skin and subcutaneous tissue 

disorders 

Alopecia (G3: 3%)a 

Nail changes (G3: 1%) 

Rash 

Musculoskeletal and 

connective tissue disorders 

Myalgia   

General disorders and 

administration site conditions 

Lethargy (G3-4: 2%) 

Flu-like symptoms (G3: 0%) 

Asthenia (G3: 0%) 

Fluid retention 

Fever (G3: 1%) 

Oral candidiasis  

Hypocalcaemia (G3: 0%) 

Hypophosphataemia (G3-4: 1%) 

Hypokalaemia (G3: 0%) 
a From the GETUG AFU15 study 
 

Tabulated list of adverse reactions in breast cancer for adjuvant therapy with DOCETAXEL KABI 

75 mg/m² in combination with doxorubicin and cyclophosphamide in patients with node-positive 

(TAX 316) and node-negative (GEICAM 9805) breast cancer - pooled data 

 



157 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 2.4%); 

Neutropenic infection 

(G3/4: 2.6%) 

    

Blood and 

lymphatic system 

disorders 

Anaemia (G3/4: 3%); 

Neutropenia 

(G3/4: 59.2%); 

Thrombocytopenia 

(G3/4: 1.6%); 

Febrile neutropenia 

(G3/4: NA) 

    

Immune system 

disorders 

  Hypersensitivity 

(G3/4: 0.6 %) 

  

Metabolism and 

nutrition disorders 

Anorexia (G3/4: 1.5%)     

Nervous system 

disorders 

Dysgeusia (G3/4: 0.6%); 

Peripheral sensory 

neuropathy 

(G3/4: < 0.1%) 

Peripheral motor 

neuropathy 

(G3/4: 0%) 

Syncope (G3/4: 0%); 

Neurotoxicity 

(G3/4: 0%); 

Somnolence (G3/4: 0%) 

Eye disorders  Conjunctivitis 

(G3/4: < 0.1%) 

Lacrimation 

increased 

(G3/4:  < 0.1%) 

  

Cardiac disorders   Arrhythmia 

(G3/4: 0.2%) 

  

Vascular disorders Hot flush (G3/4: 0.5%) Hypotension 

(G3/4: 0%); 

Phlebitis 

(G3/4: 0%) 

Lymphoedema 

(G3/4: 0%) 

Respiratory, 

thoracic and 

mediastinal 

disorders 

  Cough (G3/4: 0%)   

Gastrointestinal 

disorders 

Nausea (G3/4: 5.0%); 

Stomatitis (G3/4: 6.0%); 

Vomiting (G3/4: 4.2%); 

Diarrhoea (G3/4: 3.4%); 

Constipation 

(G3/4: 0.5%) 

Abdominal pain 

(G3/4: 0.4%) 

 

Skin and 

subcutaneous tissue 

disorders 

Alopecia 

( persisting: < 3%); 

Skin disorder  

(G3/4: 0.6%); 

Nail disorders 

(G3/4: 0.4%) 

    

Musculoskeletal 

and connective 

tissue disorders 

Myalgia (G3/4: 0.7%); 

Arthralgia (G3/4: 0.2%) 

    

Reproductive Amenorrhoea      



158 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

system and breast 

disorders 

(G3/4: NA) 

General disorders 

and administration 

site conditions 

Asthenia  

(G3/4: 10.0%); 

Pyrexia (G3/4: NA); 

Oedema peripheral 

(G3/4: 0.2%) 

    

Investigations   Weight increased 

(G3/4: 0%); 

Weight decreased 

(G3/4: 0.2%) 

  

 

Description of selected adverse reactions for adjuvant therapy with DOCETAXEL KABI 75 mg/m² in 

combination with doxorubicin and cyclophosphamide in patients with node-positive (TAX 

316) and node-negative (GEICAM 9805) breast cancer 

 

Nervous system disorders 

 In study TAX316 peripheral sensory neuropathy started during the treatment period and persisted into 

the follow-up period in 84 patients (11.3%) in TAC arm and 15 patients (2 %) in FAC arm. At the end 

of the follow-up period (median follow-up time of 8 years), peripheral sensory neuropathy was 

observed to be ongoing in 10 patients (1.3%) in TAC arm, and in 2 patients (0.3%) in FAC arm. 

In GEICAM 9805 study peripheral sensory neuropathy that started during the treatment 

period persisted into the follow-up period in 10 patients (1.9%) in TAC arm and 4 patients 

(0.8 %) in FAC arm. At the end of the follow-up period (median follow-up time of 10 years 

and 5 months), peripheral sensory neuropathy was observed to be ongoing in 3 patients 

(0.6%) in TAC arm, and in 1 patient (0.2%) in FAC arm. 
 

Cardiac disorders 

In study TAX316, 26 patients (3.5%) in the TAC arm and 17 patients (2.3%) in the FAC arm 

experienced congestive heart failure. All except one patient in each arm were diagnosed with CHF 

more than 30 days after the treatment period. Two patients in the TAC arm and 4 patients in the FAC 

arm died because of cardiac failure. 

In GEICAM 9805 study, 3 patients (0.6 %) in TAC arm and 3 patients (0.6 %) in FAC arm developed 

congestive heart failure during the follow-up period.  At the end of the follow-up period (actual 

median follow-up time of 10 years and 5 months), no patients had CHF in TAC arm and 1 patient in 

TAC arm died because of dilated cardiomyopathy, and CHF was observed to be ongoing in 1 patient 

(0.2%) in FAC arm. 

 

Skin and subcutaneous tissue disorders 

In study TAX316 alopecia persisting into the follow-up period after the end of chemotherapy was 

reported in 687 of 744 TAC patients (92.3%) and 645 of 736 FAC patients (87.6%). 

At the end of the follow-up period (actual median follow-up time of 8 years), alopecia was observed to 

be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%). 

In GEICAM 9805 study alopecia  that started during the treatment period and  persisted into the 

follow-up period and was observed to be ongoing in 49 patients (9.2 %) in TAC arm and 35 patients 

(6.7 %) in FAC arm. Alopecia related to study drug started or worsened during the follow-up period in 

42 patients (7.9 %) in TAC arm and 30 patients (5.8 %) in FAC arm. At the end of the follow-up 

period (median follow-up time of 10 years and 5 months), alopecia was observed to be ongoing in 3 

patients (0.6%) in TAC arm, and in 1 patient (0.2%) in FAC arm.   

 

 

 



159 

Reproductive system and breast disorders 

 In TAX316 amenorrhoea that started during the treatment period and persisted into the follow-up 

period after the end of chemotherapy was reported in 202 of 744 TAC patients (27.2%) and 125 of 736 

FAC patients (17.0%). Amenorrhea was observed to be ongoing at the end of the follow-up period 

(median follow-up time of 8 years) in 121 of 744 TAC patients (16.3%) and 86 FAC patients (11.7%). 

In GEICAM 9805 study amenorrhoea that started during the treatment period and persisted into the 

follow-up period was observed to be ongoing in 18 patients (3.4 %) in TAC arm and 5 patients (1.0 %) 

in FAC arm. At the end of the follow-up period (median follow-up time of 10 years and 5 months), 

amenorrhoea was observed to be ongoing in 7 patients (1.3%) in TAC arm, and in 4 patients (0.8%) in 

FAC arm. 

 

General disorders and administration site conditions 

 In study TAX316 peripheral oedema that started during the treatment period and persisted into the 

follow-up period after the end of chemotherapy was observed in 119 of 744 TAC patients (16.0%) and 

23 of 736 FAC patients (3.1%). At the end of the follow-up period (actual median follow-up time of 8 

years), peripheral oedema was ongoing in19 TAC patients (2.6%) and 4 FAC patients (0.5%).  

In study TAX316 lymphoedema that started during the treatment period and persisted into the follow-

up period after the end of chemotherapy was reported in 11 of 744 TAC patients (1.5%) and 1 of 736 

FAC patients (0.1%). At the end of the follow-up period (actual median follow-up time of 8 years), 

lymphoedema was observed to be ongoing in 6 TAC patients (0.8%) and 1 FAC patient (0.1%). 

In study TAX316 asthenia that started during the treatment period and persisted into the follow-up 

period after the end of chemotherapy was reported in 236 of 744 TAC patients (31.7%) and 180 of 736 

FAC patients (24.5%). At the end of the follow-up period (actual median follow-up time of 8 years), 

asthenia was observed to be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%). 

 

In study GEICAM 9805 peripheral oedema that started during the treatment period persisted into the 

follow-up period in 4 patients (0.8%) in TAC arm and in 2 patients (0.4%) in FAC arm. At the end of 

the follow-up period (median follow-up time of 10 years and 5 months), no patients (0%) in TAC arm 

had peripheral oedema and it was observed to be ongoing in 1 patient (0.2%) in FAC arm. 

Lymphoedema that started during the treatment period persisted into the follow-up period in 5 patients 

(0.9%) in TAC arm and 2 patients (0.4 %) in FAC arm. At the end of the follow-up period, 

lymphoedema was observed to be ongoing in 4 patients (0.8%) in TAC arm, and in 1 patient (0.2%) in 

FAC arm.  

Asthenia that started during the treatment period and persisted into the follow-up period was observed 

to be ongoing in 12 patients (2.3 %) in TAC arm and 4 patients (0.8 %) in FAC arm. At the end of the 

follow-up period, asthenia was observed to be ongoing in 2 patients (0.4%) in TAC arm, and in 2 

patients (0.4%) in FAC arm. 

 

Acute leukaemia / Myelodysplastic syndrome 

After 10 years of follow up in study TAX316, acute leukaemia was reported in 3 of 744 TAC patients 

(0.4%) and in 1 of 736 FAC patients (0.1%). One TAC patient (0.1%) and 1 FAC patient (0.1%) died 

due to AML during the follow-up period (median follow-up time of 8 years). Myelodysplastic 
syndrome was reported in 2 of 744 TAC patients (0.3%) and in 1 of 736 FAC patients (0.1%). 

After 10 years of follow-up in GEICAM 9805 STUDY, acute leukaemia occurred in 1 of 532 (0.2%) 

patients in TAC arm. No cases were reported in patients in FAC arm. No patient was diagnosed with 

myelodysplastic syndrome in either treatment groups. 

 

Neutropenic complications 

Table below shows that the incidence of Grade 4 neutropenia, febrile neutropenia and neutropenic 

infection was decreased in patients who received primary G-CSF prophylaxis after it was made 

mandatory in the TAC arm – GEICAM study. 

 

 

 

 

 



160 

Neutropenic complications in patients receiving TAC with or without primary G-CSF prophylaxis 

(GEICAM 9805) 

 

 Without primary 

G-CSF prophylaxis 

(n = 111) 

n (%) 

With primary 

G-CSF prophylaxis 

(n = 421) 

n (%) 

Neutropenia (Grade 4) 104 (93.7) 135 (32.1) 

Febrile neutropenia 28 (25.2) 23 (5.5) 

Neutropenic infection 14 (12.6) 21 (5.0) 

Neutropenic infection 

(Grade 3-4) 

2 (1.8) 5 (1.2) 

 

Tabulated list of adverse reactions in gastric adenocarcinoma center for DOCETAXEL KABI 

75 mg/m² in combination with cisplatin and 5-fluorouracil 

 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse reactions 

Infections and 

infestations 

Neutropenic infection; 

Infection (G3/4: 11.7%) 

  

Blood and lymphatic 

system disorders 

Anaemia (G3/4: 20.9%); 

Neutropenia (G3/4: 83.2%); 

Thrombocytopenia (G3/4: 8.8%); 

Febrile neutropenia  

  

Immune system 

disorders 

Hypersensitivity (G3/4: 1.7%)   

Metabolism and 

nutrition disorders 

Anorexia (G3/4: 11.7%)   

Nervous system 

disorders 

Peripheral sensory neuropathy 

(G3/4: 8.7%) 

Dizziness (G3/4: 2.3%); 

Peripheral motor neuropathy 

(G3/4: 1.3%) 

Eye disorders   Lacrimation increased (G3/4: 0%) 

Ear and labyrinth 

disorders 

  Hearing impaired (G3/4: 0%) 

Cardiac disorders   Arrhythmia (G3/4: 1.0%) 

Gastrointestinal 

disorders 

Diarrhoea (G3/4: 19.7%); 

Nausea (G3/4: 16%); 

Stomatitis (G3/4: 23.7%); 

Vomiting (G3/4: 14.3%) 

Constipation (G3/4: 1.0%); 

Gastrointestinal pain (G3/4: 1.0%); 

Oesophagitis/dysphagia/ 

odynophagia (G3/4: 0.7%) 

Skin and subcutaneous 

tissue disorders 

Alopecia (G3/4: 4.0%) Rash pruritus (G3/4: 0.7%); 

Nail disorders (G3/4: 0.7%); 

Skin exfoliation (G3/4: 0%) 

General disorders and 

administration site 

conditions 

Lethargy (G3/4: 19.0%); 

Fever (G3/4: 2.3%); 

Fluid retention (severe/life-

threatening: 1%) 

  

 

Description of selected adverse reactions in gastric adenocarcinoma cancer for DOCETAXEL KABI 

75 mg/m2 in combination with cisplatin and 5-fluorouracil 

 



161 

Blood and lymphatic system disorders 

Febrile neutropenia and neutropenic infection occurred in 17.2% and 13.5% of patients respectively, 

regardless of G-CSF use. G-CSF was used for secondary prophylaxis in 19.3% of patients (10.7% of 

the cycles). Febrile neutropenia and neutropenic infection occurred respectively in 12.1% and 3.4% of 

patients when patients received prophylactic G-CSF, in 15.6% and 12.9% of patients without 

prophylactic G-CSF (see section 4.2). 

 

Tabulated list of adverse reactions in head and neck cancer for DOCETAXEL KABI 75 mg/m² in 

combination with cisplatin and 5-fluorouracil  

 

• Induction chemotherapy followed by radiotherapy (TAX 323)  
 

MedDRA system 

organ classes 

Very common adverse 

reactions 

 

Common adverse 

reactions 

 

Uncommon 

adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 6.3%); 

Neutropenic infection 

    

Neoplasms benign, 

malignant and 

unspecified (incl 

cysts and polyps) 

  Cancer pain (G3/4: 0.6%)   

Blood and lymphatic 

system disorders 

Neutropenia 

(G3/4: 76.3%); 

Anaemia (G3/4: 9.2%); 

Thrombocytopenia 

(G3/4: 5.2%) 

Febrile neutropenia   

Immune system 

disorders 

  Hypersensitivity (no 

severe) 

  

Metabolism and 

nutrition disorders 

Anorexia (G3/4: 0.6%)     

Nervous system 

disorders 

Dysgeusia/Parosmia; 

Peripheral sensory 

neuropathy (G3/4: 0.6%) 

Dizziness   

Eye disorders   Lacrimation increased; 

Conjunctivitis  

  

Ear and labyrinth 

disorders 

  Hearing impaired   

Cardiac disorders   Myocardial ischemia 

(G3/4: 1.7%) 

Arrhythmia 

(G3/4: 0.6%) 

Vascular disorders   Venous disorder 

(G3/4: 0.6%) 

  

Gastrointestinal 

disorders 

Nausea (G3/4: 0.6%); 

Stomatitis (G3/4: 4.0%); 

Diarrhoea (G3/4: 2.9%); 

Vomiting (G3/4: 0.6%) 

Constipation; 

Esophagitis/dysphagia/ 

odynophagia 

(G3/4: 0.6%); 

Abdominal pain; 

Dyspepsia; 

Gastrointestinal 

haemorrhage 

(G3/4: 0.6%)  

  



162 

MedDRA system 

organ classes 

Very common adverse 

reactions 

 

Common adverse 

reactions 

 

Uncommon 

adverse 

reactions 

Skin and 

subcutaneous tissue 

disorders 

Alopecia (G3/4: 10.9%) Rash pruritic; 

Dry skin; 

Skin exfoliative 

(G3/4: 0.6%) 

  

Musculoskeletal and 

connective tissue 

disorders 

  Myalgia (G3/4: 0.6%)   

General disorders and 

administration site 

conditions 

Lethargy (G3/4: 3.4%); 

Pyrexia (G3/4: 0.6%); 

Fluid retention; 

Oedema 

    

Investigations   Weight increased   

 

• Induction chemotherapy followed by chemoradiotherapy (TAX 324)  
 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 3.6%) 

  

Neutropenic 

infection 

  

Neoplasms benign, 

malignant and 

unspecified (incl 

cysts and polyps) 

  Cancer pain 

(G3/4: 1.2%) 

  

Blood and lymphatic 

system disorders 

Neutropenia 

(G3/4: 83.5%); 

Anaemia (G3/4: 12.4%); 

Thrombocytopenia 

(G3/4: 4.0%); 

Febrile neutropenia 

    

Immune system 

disorders 

    Hypersensitivity 

Metabolism and 

nutrition disorders 

Anorexia (G3/4: 12.0%)     

Nervous system 

disorders 

Dysgeusia/Parosmia 

(G3/4: 0.4%); 

Peripheral sensory 

neuropathy (G3/4: 1.2%) 

Dizziness 

(G3/4: 2.0%); 

Peripheral motor 

neuropathy 

(G3/4: 0.4%) 

  

Eye disorders   Lacrimation 

increased 

Conjunctivitis 

Ear and labyrinth 

disorders 

Hearing impaired 

(G3/4: 1.2%) 

    

Cardiac disorders   Arrhythmia 

(G3/4: 2.0%) 

Ischemia myocardial 

Vascular disorders     Venous disorder 



163 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Gastrointestinal 

disorders 

Nausea (G3/4: 13.9%); 

Stomatitis (G3/4: 20.7%); 

Vomiting (G3/4: 8.4%); 

Diarrhoea (G3/4: 6.8%); 

Esophagitis/dysphagia/ 

odynophagia 

(G3/4: 12.0%); 

Constipation (G3/4: 0.4%) 

Dyspepsia 

(G3/4: 0.8%); 

Gastrointestinal pain 

(G3/4: 1.2%); 

Gastrointestinal 

haemorrhage 

(G3/4: 0.4%) 

  

Skin and 

subcutaneous tissue 

disorders 

Alopecia (G3/4: 4.0%); 

Rash pruritic 

Dry skin; 

Desquamation 

  

Musculoskeletal, 

connective tissue 

bone disorders 

  Myalgia 

(G3/4: 0.4%) 

  

General disorders and 

administration site 

conditions 

Lethargy (G3/4: 4.0%); 

Pyrexia (G3/4: 3.6%); 

Fluid retention (G3/4: 1.2); 

Oedema (G3/4: 1.2%) 

    

Investigations Weight decreased   Weight increased 

 

Post-marketing experience 

 

Neoplasms benign, malignant and unspecified (incl cysts and polyps) 

Second primary malignancies (frequency not known), including non-Hodgkin lymphoma have been 

reported in association with docetaxel when used in combination with other anticancer treatments 

known to be associated with second primary malignancies. Acute myeloid leukemia and 

myelodysplastic syndrome have been reported (frequency uncommon) in pivotal clinical studies in 

breast cancer with TAC regimen. 

 

Blood and lymphatic system disorders 

Bone marrow suppression and other haematologic adverse reactions have been reported. Disseminated 

intravascular coagulation (DIC), often in association with sepsis or multi-organ failure, has been 

reported. 

Immune system disorders 

Some cases of anaphylactic shock, sometimes fatal, have been reported. 

Hypersensitivity reactions (frequency not known) have been reported with docetaxel in patients who 

previously experienced hypersensitivity reactions to paclitaxel. 

 

Nervous system disorders 

Rare cases of convulsion or transient loss of consciousness have been observed with docetaxel 

administration. These reactions sometimes appear during the infusion of the medicinal product. 

 

Eye disorders 

Very rare cases of transient visual disturbances (flashes, flashing lights, scotomata) typically occurring 

during infusion of the medicinal product and in association with hypersensitivity reactions have been 

reported. These were reversible upon discontinuation of the infusion. Cases of lacrimation with or 

without conjunctivitis, as cases of lacrimal duct obstruction resulting in excessive tearing have been 

rarely reported. Cases of cystoid macular oedema (CMO) have been reported in patients treated with 

docetaxel. 

 

Ear and labyrinth disorders 

Rare cases of ototoxicity, hearing impaired and/or hearing loss have been reported. 



164 

Cardiac disorders 

Rare cases of myocardial infarction have been reported. 

Ventricular arrhythmia including ventricular tachycardia (frequency not known), sometimes fatal, has 

been reported in patients treated with docetaxel in combination regimens including doxorubicin, 5-

fluorouracil and/ or cyclophosphamide. 

 

Vascular disorders 

Venous thromboembolic events have rarely been reported. 

Respiratory, thoracic and mediastinal disorders 

Acute respiratory distress syndrome and cases of interstitial pneumonia/ pneumonitis, interstitial lung 
disease, pulmonary fibrosis and respiratory failure sometimes fatal have rarely been reported. Rare 

cases of radiation pneumonitis have been reported in patients receiving concomitant radiotherapy. 

 

Gastrointestinal disorders 

Rare cases of enterocolitis, including colitis, ischemic colitis, and neutropenic enterocolitis, have been 

reported with a potential fatal outcome (frequency not known). 

Rare occurrences of dehydration have been reported as a consequence of gastrointestinal events 

including enterocolitis and gastrointestinal perforation.  

Rare cases of ileus and intestinal obstruction have been reported. 

 

Hepatobiliary disorders 

Very rare cases of hepatitis, sometimes fatal primarily in patients with pre-existing liver disorders, 

have been reported. 

 

Skin and subcutaneous tissue disorders 

Cases of cutaneous lupus erythematosus, bullous eruptions such as erythema multiforme and severe 

cutaneous adverse reactions such as Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis 

(TEN) and Acute Generalized Exanthematous Pustulosis (AGEP) have been reported with docetaxel.  

Scleroderma-like changes usually preceded by peripheral lymphoedema have been reported with 

docetaxel. Cases of permanent alopecia (frequency not known) have been reported. 

 

Renal and urinary disorders 

Renal insufficiency and renal failure have been reported. In about 20% of these cases there were no 

risk factors for acute renal failure such as concomitant nephrotoxic medicinal products and 

gastrointestinal disorders. 

 

General disorders and administration site conditions 

Radiation recall phenomena have rarely been reported. 

Injection site recall reaction (recurrence of skin reaction at a site of previous extravasation following 

administration of docetaxel at a different site) has been observed at the site of previous extravasation 

(frequency not known). 

Fluid retention has not been accompanied by acute episodes of oliguria or hypotension. Dehydration 

and pulmonary oedema have rarely been reported. 

 

Metabolism and nutrition disorders 

Cases of electrolyte imbalance have been reported. Cases of hyponatraemia have been reported, 

mostly associated with dehydration, vomiting and pneumonia. Hypokalaemia, hypomagnesaemia, and 

hypocalcaemia were observed, usually in association with gastrointestinal disorders and in particular 

with diarrhoea. 

 

Reporting of suspected adverse reactions 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

 



165 

4.9 Overdose 

 

There were a few reports of overdose. There is no known antidote for docetaxel overdose. In case of 

overdose, the patient should be kept in a specialised unit and vital functions closely monitored. In 

cases of overdose, exacerbation of adverse events may be expected. The primary anticipated 

complications of overdose would consist of bone marrow suppression, peripheral neurotoxicity and 

mucositis. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. 

Other appropriate symptomatic measures should be taken, as needed. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: antineoplastic agents, plant alkaloids and other natural products, taxanes, 

ATC Code: L01CD02  

 

Mechanism of action 

 

Docetaxel is an antineoplastic agent which acts by promoting the assembly of tubulin into stable 

microtubules and inhibits their disassembly which leads to a marked decrease of free tubulin. The 

binding of docetaxel to microtubules does not alter the number of protofilaments. 

 

Docetaxel has been shown in vitro to disrupt the microtubular network in cells which is essential for 

vital mitotic and interphase cellular functions. 

 

Pharmacodynamic effects 

 

Docetaxel was found to be cytotoxic in vitro against various murine and human tumour cell lines and 

against freshly excised human tumour cells in clonogenic assays. Docetaxel achieves high intracellular 

concentrations with a long cell residence time. In addition, docetaxel was found to be active on some 

but not all cell lines over expressing the p-glycoprotein which is encoded by the multidrug resistance 

gene. In vivo, docetaxel is schedule independent and has a broad spectrum of experimental anti-tumour 

activity against advanced murine and human grafted tumours. 

 

Clinical efficacy and safety 

 

Breast cancer 

 

DOCETAXEL KABI in combination with doxorubicin and cyclophosphamide: adjuvant therapy 

 

Patients with operable node-positive breast cancer (TAX 316) 

 

Data from a multi-centre open-label randomised study support the use of docetaxel for the adjuvant 

treatment of patients with operable node-positive breast cancer and KPS ≥ 80%, between 18 and 

70 years of age. After stratification according to the number of positive lymph nodes (1-3, 

4+), 1491 patients were randomised to receive either docetaxel 75 mg/m2 administered 1-hour after 

doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (TAC arm), or doxorubicin 50 mg/m2 

followed by fluorouracil 500 mg/m2 and cyclosphosphamide 500 mg/m2 (FAC arm). Both regimens 

were administered once every 3 weeks for 6 cycles. Docetaxel was administered as a 1-hour infusion, 

all other medicinal products were given as intravenous bolus on day one. G-CSF was administered as 

secondary prophylaxis to patients who experienced complicated neutropenia (febrile neutropenia, 

prolonged neutropenia, or infection). Patients on the TAC arm received antibiotic prophylaxis with 

ciprofloxacin 500 mg orally twice daily for 10 days starting on day 5 of each cycle, or equivalent. In 

both arms, after the last cycle of chemotherapy, patients with positive oestrogen and/or progesterone 

receptors received tamoxifen 20 mg daily for up to 5 years. Adjuvant radiation therapy was prescribed 

according to guidelines in place at participating institutions and was given to 69% of patients who 



166 

received TAC and 72% of patients who received FAC. Two interim analyses and one final analysis 

were performed. The first interim analysis was planned 3 years after the date when half of study 

enrolment was done. The second interim analysis was done after 400 DFS events had been recorded 

overall, which led to a median follow-up of 55 months. The final analysis was performed when all 

patients had reached their 10-year follow-up visit (unless they had a DFS event or were lost to follow 

up before). Disease-free survival (DFS) was the primary efficacy endpoint and Overall survival (OS) 

was the secondary efficacy endpoint. 

 

A final analysis was performed with an actual median follow up of 96 months. Significantly longer 

disease-free survival for the TAC arm compared to the FAC arm was demonstrated. Incidence of 

relapses at 10 years was reduced in patients receiving TAC compared to those who received FAC 

(39% versus 45%, respectively) i.e. an absolute risk reduction by 6% (p = 0.0043). Overall survival at 

10 years was also significantly increased with TAC compared to FAC (76% versus 69%, respectively) 

i.e. an absolute reduction of the risk of death by 7% (p = 0.002). As the benefit observed in patients 

with 4+ nodes was not statistically significant on DFS and OS, the positive benefit/risk ratio for TAC 

in patients with 4+ nodes was not fully demonstrated at the final analysis. 

 

Overall, the study results demonstrate a positive benefit risk ratio for TAC compared to FAC. 

 

TAC-treated patient subsets according to prospectively defined major prognostic factors were 

analysed:  

 

  Disease free survival Overall Survival 

Patient 

subset 

Number 

of patients 

Hazard 

ratio* 

95% CI p = Hazard 

ratio* 

95% CI p = 

No of 

positive 

nodes 

Overall 

1-3 

4+ 

 

 

 

745 

467 

278 

 

 

 

0.80 

0.72 

0.87 

 

 

 

0.68-0.93 

0.58-0.91 

0.70-1.09 

 

 

 

0.0043 

0.0047 

0.2290 

 

 

 

0.74 

0.62 

0.87 

 

 

 

0.61-0.90 

0.46-0.82 

0.67-1.12 

 

 

 

0.0020 

0.0008 

0.2746 

*a hazard ratio of less than 1 indicates that TAC is associated with a longer disease-free survival and 

overall survival compared to FAC  

 

Patients with operable node-negative breast cancer eligible to receive chemotherapy (GEICAM 9805) 

 

Data from a multi-centre open-label randomisedtrial support the use of DOCETAXEL KABI for the 

adjuvant treatment of patients with operable node-negative breast cancer eligible to receive 

chemotherapy. 1060 patients were randomised to receive either DOCETAXEL KABI 75 mg/m2 

administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (539 patients in 

TAC arm), or doxorubicin 50 mg/m2 followed by fluorouracil 500 mg/m2 and cyclosphosphamide 

500 mg/m2 (521 patients in FAC arm), as adjuvant treatment of operable node-negative breast cancer 

patients with high risk of relapse according to 1998 St. Gallen criteria (tumour size > 2 cm and/or 

negative ER and PR and/or high histological/nuclear grade (grade 2 to 3) and /or age < 35 years).). 

Both regimens were administered once every 3 weeks for 6 cycles. DOCETAXEL KABI was 

administered as a 1-hour infusion, all other medicinal product were given intraveinously on day 1 

every three weeks. Primary prophylactic G-CSF was made mandatory in TAC arm after 230 patients 

were randomised. The incidence of Grade 4 neutropenia, febrile neutropenia and neutropenic infection 

was decreased in patients who received primary G-CSF prophylaxis (see section 4.8). In both arms, 

after the last cycle of chemotherapy, patients with ER+ and/or PgR+ tumours received tamoxifen 

20 mg once a day for up to 5 years. Adjuvant radiation therapy was administered according to 

guidelines in place at participating institutions and was given to 57.3% of patients who received TAC 

and 51.2% of patients who received FAC. 

 



167 

One primary analysis and one updated analysis were performed. The primary analysis was done when 

all patients had a follow-up of greater than 5 years (median follow-up time of 77 months). The updated 

analysis was performed when all patients had reached their 10-year (median follow up time of 10 

years and 5 months) follow-up visit (unless they had a DFS event or were lost to follow-up 

previously). Disease-free survival (DFS) was the primary efficacy endpoint and Overall survival (OS) 

was the secondary efficacy endpoint. 

 

Athe median follow-up time of 77 months, significantly longer disease-free survival for the TAC arm 

compared to the FAC arm was demonstrated. TAC-treated patients had a 32% reduction in the risk of 

relapse compared to those treated with FAC (hazard ratio = 0.68, 95% CI (0.49-0.93), p = 0.01). At the 

median follow up time of 10 years and 5 months, TAC-treated patients had a 16,5% reduction in the 

risk of relapse compared to those treated with FAC (hazard ratio = 0.84, 95% CI (0.65-1.08), 

p=0.1646). DFS data were not statistically significant but were still associated with a positive trend in 

favour of TAC.   

 

At the median follow-up time of 77 months overall survival (OS) was longer in the TAC arm with 

TAC-treated patients having a 24% reduction in the risk of death compared to FAC (hazard ratio = 

0.76, 95% CI (0.46-1.26, p = 0.29). However, the distribution of OS was not significantly different 

between the 2 groups. 

At the median follow up time of 10 years and 5 months, TAC-treated patients had a 9% reduction in 

the risk of death compared to FAC-treated patients (hazard ratio = 0.91, 95% CI (0.63-1.32)).  

The survival rate was 93.7% in the TAC arm and 91.4 % in the FAC arm, at the 8-year follow-up time 

point, and 91.3 % in the TAC arm and 89 % in the FAC arm, at the 10-year follow-up time point. 

 

The positive benefit risk ratio for TAC compared to FAC remained unchanged.   

 

TAC-treated patient subsets according to prospectively defined major prognostic factors were analysed 

in the primary analysis (at the median follow-up time of 77 months) (see table below): 

 

Subset Analyses-Adjuvant Therapy in Patients with Node-negative Breast Cancer Study 

(Intent-to-Treat Analysis) 

 

Patient subset Number of patients 

in TAC group 

Disease Free Survival 

Hazard ratio* 95% CI 

Overall 539 0.68 0.49-0.93 

Age category 1 

<50 years  

≥50 years 

 

260 

279  

 

0.67 

0.67  

 

0.43-1.05 

0.43-1.05 

Age category 2 

<35 years 

≥35 years 

 

42 

497 

 

0.31 

0.73 

 

0.11-0.89 

0.52-1.01 

Hormonal receptor 

status 

Negative  

Positive 

 

 

195 

344 

 

 

0.7 

0.62 

 

 

0.45-1.1 

0.4-0.97 

Tumour size 

≤2 cm  

>2 cm 

 

285 

254 

 

0.69 

0.68 

 

0.43-1.1 

0.45-1.04 

Histological grade 

Grade1 (includes grade 

not assessed) 

Grade 2  

Grade 3 

 

64 

 

216 

259 

 

0.79 

 

0.77 

0.59 

 

0.24-2.6 

 

0.46-1.3 

0.39-0.9 

Menopausal status 

Pre-Menopausal  

Post-Menopausal  

 

285 

254 

 

0.64 

0.72 

 

0.40-1 

0.47-1.12 



168 

*a hazard ratio (TAC/FAC) of less than 1 indicates that TAC is associated with a longer disease free 

survival compared to FAC. 

 

Exploratory subgroup analyses for disease-free survival for patients who meet the 2009 St. Gallen 

chemotherapy criteria – (ITT population) were performed and presented here below 

 
 TAC 

 

FAC 

 

Hazard ratio 

(TAC/FAC) 

 

 

Subgroups (n=539) (n=521) (95% CI) p-value 

Meeting relative 

 indication 

for chemotherapya 

    

No 18/214 

(8.4%) 

26/227 

(11.5%) 

0.796 

(0.434 - 1.459) 

0.4593 

Yes 48/325 

(14.8%) 

69/294 

(23.5%) 

0.606 

(0.42 - 0.877) 

0.0072 

TAC = docetaxel, doxorubicin and cyclophosphamide 

FAC = 5-fluorouracil, doxorubicin and cyclophosphamide 

CI = confidence interval 

ER = oestrogen receptor 

PR = progesterone receptor 
a ER/PR-negative or Grade 3 or tumour size > 5 cm 

 

The estimated hazard ratio was using Cox proportional hazard model with treatment group as the 

factor. 

 

DOCETAXEL KABI as single agent 

 

Two randomised phase III comparative studies, involving a total of 326 alkylating or 

392 anthracycline failure metastatic breast cancer patients, have been performed with docetaxel at the 

recommended dose and regimen of 100 mg/m² every 3 weeks. 

 

In alkylating-failure patients, docetaxel was compared to doxorubicin (75 mg/m² every 3 weeks). 

Without affecting overall survival time (docetaxel 15 months vs. doxorubicin 14 months, p = 0.38) or 

time to progression (docetaxel 27 weeks vs. doxorubicin 23 weeks, p = 0.54), docetaxel increased 

response rate (52% vs. 37%, p = 0.01) and shortened time to response (12 weeks vs. 23 weeks, 

p= 0.007). Three docetaxel patients (2%) discontinued the treatment due to fluid retention, whereas 

15 doxorubicin patients (9%) discontinued due to cardiac toxicity (three cases of fatal congestive heart 

failure). 

 

In anthracycline-failure patients, docetaxel was compared to the combination of mitomycin C and 

vinblastine (12 mg/m² every 6 weeks and 6 mg/m² every 3 weeks). Docetaxel increased response rate 

(33% vs. 12%, p < 0.0001), prolonged time to progression (19 weeks vs. 11 weeks, p= 0.0004) and 

prolonged overall survival (11 months vs. 9 months, p= 0.01). 

 

During these two phase III studies, the safety profile of docetaxel was consistent with the safety profile 

observed in phase II studies (see section 4.8). 

 

An open-label, multi-centre, randomised phase III study was conducted to compare docetaxel 
monotherapy and paclitaxel in the treatment of advanced breast cancer in patients whose previous 

therapy should have included an anthracycline. A total of 449 patients were randomised to receive 

either docetaxel monotherapy 100 mg/m² as a 1 hour infusion or paclitaxel 175 mg/m² as a 3 hour 

infusion. Both regimens were administered every 3 weeks. 

Without affecting the primary endpoint, overall response rate (32% vs 25%, p = 0.10), docetaxel 

prolonged median time to progression (24.6 weeks vs 15.6 weeks; p < 0.01) and median survival 

(15.3 months vs 12.7 months; p = 0.03). 



169 

More grade 3/4 adverse events were observed for docetaxel monotherapy (55.4%) compared to 

paclitaxel (23.0%). 

 

DOCETAXEL KABI in combination with doxorubicin 

 

One large randomised phase III study, involving 429 previously untreated patients with metastatic 

disease, has been performed with doxorubicin (50 mg/m²) in combination with docetaxel (75 mg/m²) 

(AT arm) versus doxorubicin (60 mg/m²) in combination with cyclophosphamide (600 mg/m²) (AC 

arm). Both regimens were administered on day 1 every 3 weeks.  

• Time to progression (TTP) was significantly longer in the AT arm versus AC arm, p = 0.0138. 
The median TTP was 37.3 weeks (95% CI: 33.4 - 42.1) in AT arm and 31.9 weeks (95% CI: 27.4 - 

36.0) in AC arm.  

• Overall response rate (ORR) was significantly higher in the AT arm versus AC arm, p = 0.009. 
The ORR was 59.3% (95% CI: 52.8 - 65.9) in AT arm versus 46.5% (95% CI: 39.8 - 53.2) in AC 

arm.  

 

In this study, AT arm showed a higher incidence of severe neutropenia (90% versus 68.6%), febrile 

neutropenia (33.3% versus 10%), infection (8% versus 2.4%), diarrhoea (7.5% versus 1.4%), asthenia 

(8.5% versus 2.4%), and pain (2.8% versus 0%) than AC arm. On the other hand, AC arm showed a 

higher incidence of severe anaemia (15.8% versus 8.5%) than AT arm, and, in addition, a higher 

incidence of severe cardiac toxicity: congestive heart failure (3.8% versus 2.8%), absolute LVEF 

decrease ≥ 20% (13.1% versus 6.1%), absolute LVEF decrease ≥ 30% (6.2% versus 1.1%). Toxic 

deaths occurred in 1 patient in the AT arm (congestive heart failure) and in 4 patients in the AC arm 

(1 due to septic shock and 3 due to congestive heart failure).  

In both arms, quality of life measured by the EORTC questionnaire was comparable and stable during 

treatment and follow-up.  

 

DOCETAXEL KABI in combination with trastuzumab 

 

Docetaxel in combination with trastuzumab was studied for the treatment of patients with metastatic 

breast cancer whose tumours overexpress HER2, and who previously had not received chemotherapy 

for metastatic disease. One hundred eighty six patients were randomised to receive docetaxel 

(100 mg/m2) with or without trastuzumab; 60% of patients received prior anthracycline-based adjuvant 

chemotherapy. Docetaxel plus trastuzumab was efficacious in patients whether or not they had 

received prior adjuvant anthracyclines. The main test method used to determine HER2 positivity in 

this pivotal study was immunohistochemistry (IHC). A minority of patients were tested using 

fluorescence in-situ hybridization (FISH). In this study, 87% of patients had disease that was IHC 3+, 

and 95% of patients entered had disease that was IHC 3+ and/or FISH positive. Efficacy results are 

summarized in the following table:  

 

Parameter Docetaxel plus trastuzumab1 

n = 92 

Docetaxel1 

n = 94 

Response rate 

(95% CI) 

61% 

(50-71) 

34% 

(25-45) 

Median duration of response 

(months) 

(95% CI)  

11.4 

(9.2-15.0) 

5.1 

(4.4-6.2) 

Median TTP (months) 

(95% CI) 

10.6 

(7.6-12.9) 

5.7 

(5.0-6.5) 

Median survival (months) 

(95% CI) 

30.52 

(26.8-ne) 

22.12 

(17.6-28.9) 

TTP = time to progression; “ne” indicates that it could not be estimated or it was not yet reached.  
1Full analysis set (intent-to-treat)  
2 Estimated median survival  



170 

 

DOCETAXEL KABI in combination with capecitabine 

 

Data from one multi-centre, randomised, controlled phase III clinical study support the use of 

docetaxel in combination with capecitabine for treatment of patients with locally advanced or 

metastatic breast cancer after failure of cytotoxic chemotherapy, including an anthracycline. In this 

study, 255 patients were randomised to treatment with docetaxel (75 mg/m2 as a 1 hour intravenous 

infusion every 3 weeks) and capecitabine (1250 mg/m2 twice daily for 2 weeks followed by 1-week 

rest period). 256 patients were randomised to treatment with docetaxel alone (100 mg/m2 as a 1 hour 

intravenous infusion every 3 weeks). Survival was superior in the docetaxel + capecitabine 

combination arm (p = 0.0126). Median survival was 442 days (docetaxel + capecitabine) vs. 352 days 

(docetaxel alone). The overall objective response rates in the all-randomised population (investigator 

assessment) were 41.6% (docetaxel + capecitabine) vs. 29.7% (docetaxel alone); p = 0.0058. Time to 

progressive disease was superior in the docetaxel + capecitabine combination arm (p < 0.0001). The 

median time to progression was 186 days (docetaxel + capecitabine) vs. 128 days (docetaxel alone). 

 

Non-small cell lung cancer 

 

Patients previously treated with chemotherapy with or without radiotherapy 

 

In a phase III study, in previously treated patients, time to progression (12.3 weeks versus 7 weeks) 

and overall survival were significantly longer for docetaxel at 75 mg/m² compared to Best Supportive 

Care. The 1-year survival rate was also significantly longer in docetaxel (40%) versus BSC (16%). 

There was less use of morphinic analgesic (p < 0.01), non-morphinic analgesics (p < 0.01), other 

disease-related medicinal products (p = 0.06) and radiotherapy (p < 0.01) in patients treated with 

docetaxel at 75 mg/m² compared to those with BSC.  

The overall response rate was 6.8% in the evaluable patients, and the median duration of response was 

26.1 weeks.  

 

DOCETAXEL KABI in combination with platinum agents in chemotherapy-naïve patients 

 

In a phase III study, 1218 patients with unresectable stage IIIB or IV NSCLC, with KPS of 70% or 

greater, and who did not receive previous chemotherapy for this condition, were randomised to either 

docetaxel (T) 75 mg/m2 as a 1 hour infusion immediately followed by cisplatin (Cis) 75 mg/m2 over 

30-60 minutes every 3 weeks (TCis), docetaxel 75 mg/m2 as a 1 hour infusion in combination with 

carboplatin (AUC 6 mg/ml.min) over 30-60 minutes every 3 weeks, or vinorelbine (V) 25 mg/m2 

administered over 6-10 minutes on days 1, 8, 15, 22 followed by cisplatin 100 mg/m2 administered on 

day 1 of cycles repeated every 4 weeks (VCis).  

 

Survival data, median time to progression and response rates for two arms of the study are illustrated 

in the following table:  

 

 TCis 

n = 408 

VCis 

n = 404 

Statistical analysis 

Overall survival 

(Primary end-point): 

   

Median survival (months) 11.3 10.1 Hazard Ratio: 1.122 

 [97.2% CI: 0.937; 1.342]* 

1-year Survival (%) 46 41 Treatment difference: 5.4% 

[95% CI: -1.1; 12.0] 

2 year Survival (%) 21 14 Treatment difference: 6.2% 

[95% CI: 0.2; 12.3] 

Median time to progression 

(weeks): 

22.0 23.0 Hazard Ratio: 1.032  

[95% CI: 0.876; 1.216] 

Overall response rate (%): 31.6 24.5 Treatment difference: 7.1% 

[95% CI: 0.7; 13.5] 



171 

*: Corrected for multiple comparisons and adjusted for stratification factors (stage of disease and 

region of treatment), based on evaluable patient population. 

 

Secondary end-points included change of pain, global rating of quality of life by EuroQoL-5D, Lung 

Cancer Symptom Scale, and changes in Karnosfky performance status. Results on these end-points 

were supportive of the primary end-points results.  

 

For docetaxel/carboplatin combination, neither equivalent nor non-inferior efficacy could be proven 

compared to the reference treatment combination VCis.  

 

Prostate cancer 

Metastatic castration-resistant prostate cancer 

 

The safety and efficacy of docetaxel in combination with prednisone or prednisolone in patients with 

metastatic castration-resistant prostate cancer were evaluated in a randomised multi-centre phase III 

study (TAX 327). A total of 1006 patients with KPS ≥ 60 were randomised to the following treatment 

groups:  

• Docetaxel 75 mg/m2 every 3 weeks for 10 cycles. 

• Docetaxel 30 mg/m2 administered weekly for the first 5 weeks in a 6 week cycle for 5 cycles. 

• Mitoxantrone 12 mg/m2 every 3 weeks for 10 cycles. 
All 3 regimens were administered in combination with prednisone or prednisolone 5 mg twice daily, 

continuously. 

 

Patients who received docetaxel every three weeks demonstrated significantly longer overall survival 

compared to those treated with mitoxantrone. The increase in survival seen in the docetaxel weekly 

arm was not statistically significant compared to the mitoxantrone control arm. Efficacy endpoints for 

the docetaxel arms versus the control arm are summarized in the following table:  

 

Endpoint 

 

Docetaxel every 3 

weeks 

Docetaxel every 

week 

Mitoxantrone 

every 3 weeks 

Number of patients 

Median survival (months) 

95% CI 

Hazard ratio 

95% CI 

p-value† * 

335 

18.9 

(17.0-21.2) 

0.761 

(0.619-0.936) 

0.0094 

334 

17.4 

(15.7-19.0) 

0.912 

(0.747-1.113) 

0.3624 

337 

16.5 

(14.4-18.6) 

- 

- 

- 

Number of patients 

PSA** response rate (%) 

95% CI 

p-value* 

291 

45.4 

(39.5-51.3) 

0.0005 

282 

47.9 

(41.9-53.9) 

< 0.0001 

300 

31.7 

(26.4-37.3) 

- 

Number of patients 

Pain response rate (%) 

95% CI 

p-value* 

153 

34.6 

(27.1-42.7) 

0.0107 

154 

31.2 

(24.0-39.1) 

0.0798 

157 

21.7 

(15.5-28.9) 

- 

Number of patients 

Tumor response rate (%) 

95% CI 

p-value* 

141 

12.1 

(7.2-18.6) 

0.1112 

134 

8.2 

(4.2-14.2) 

0.5853 

137 

6.6 

(3.0-12.1) 

- 
†Stratified log-rank test  

*Threshold for statistical significance = 0.0175  

**PSA: Prostate-Specific Antigen  

 

Given the fact that docetaxel every week presented a slightly better safety profile than docetaxel every 

3 weeks, it is possible that certain patients may benefit from docetaxel every week.  



172 

 

No statistical differences were observed between treatment groups for Global Quality of Life. 

 

Metastatic hormone-sensitive prostate cancer 

 

STAMPEDE study 

 

The safety and efficacy of docetaxel administered concomitantly with standard of care (ADT) in 

patients with high-risk locally advanced or metastatic hormone-sensitive prostate cancer were 

evaluated in a randomised multi-centre, multi-arm multi-stage (MAMS) study with a seamless phase 

II/III design (STAMPEDE – MRC PR08). A total of 1776 male patients were allocated to the 
treatment arms of interest:  

• Standard of care + docetaxel 75 mg/m², administered every 3 weeks for 6 cycles 

• Standard of care alone  

Docetaxel regimen was administered in combination with prednisone or prednisolone 5 mg twice daily 

continuously.  

Among the 1776 randomised patients 1086 (61%) had metastatic disease, 362 were randomised to 

docetaxel in combination with standard of care, 724 received standard of care alone.  

 

In these metastatic prostate cancer patients, the median overall survival was significantly longer in 

docetaxel treatment groups than in the standard of care alone group, with a median overall survival 19 

months longer with the addition of docetaxel to standard of care (HR =  0.76, 95% CI = 0.62-0.92, 

p=0.005).  

 

Efficacy results in metastatic prostate cancer patients for docetaxel arm versus control arm are 

summarized in the following table: 

 

Efficacy of docetaxel in combination with prednisone or prednisolone and standard of care in the 

treatment of patients with metastatic hormone-sensitive prostate cancer (STAMPEDE) 

 

Endpoint 

 

Docetaxel + standard of care 

 

Standard of care alone 

Number of metastatic prostate 

cancer patients 

 

Median overall survival (months)  

95% CI 

362 

 

 

62 

51-73 

724 

 

 

43 

40-48 

Adjusted hazard ratio 

95% CI 

p-valuea 

0.76 

(0.62-0.92) 

0.005 

Failure-Free survivalb    

Median (months) 

95% CI 

20.4 

16.8-25.2 

12 

9.6-12 

Adjusted hazard ratio 

95% CI 

p-valuea 

0.66 

(0.57-0.76) 

< 0.001 

a p-value calculated from the likelihood ratio test and adjusted for all stratification factors 

(except center and planned hormone therapy) and stratified by trial period 
b Failure-free survival: time from randomization to first evidence of at least one of: biochemical 

failure (defined as a rise in PSA of 50% above the within-24-week nadir and above 4 ng/mL 

and confirmed by retest or treatment); progression either locally, in lymph nodes, or in distant 

metastases; skeletal-related event; or death from prostate cancer. 

 



173 

CHAARTED study 

 

The safety and efficacy of docetaxel administered at the beginning of androgen-deprivation therapy 

(ADT) in patients with metastatic hormone-sensitive prostate cancer were evaluated in a randomised 

Phase III multi-centre study (CHAARTED). A total of 790 male patients were allocated to the 2 

treatment groups.  

• ADT + docetaxel 75 mg/m² given at the beginning of ADT, administered every 3 weeks 

for 6 cycles 

• ADT alone   

 

The median overall survival was significantly longer in docetaxel treatment group than in the ADT 

alone group, with a median overall survival 13.6 months longer with the addition of docetaxel to ADT 

(hazard ratio (HR) = 0.61, 95% confidence interval (CI) = 0.47-0.80, p=0.0003).  

 

Efficacy results or the docetaxel arm versus the control arm are summarized in the following table: 

 

Efficacy of docetaxel and ADT in the treatment of patients with metastatic hormone-sensitive prostate 

cancer (CHAARTED) 

 

Endpoint 

 

Docetaxel +ADT  

 

ADT alone 

Number of patients 

Median overall survival (months) 

All patients 

95% CIAdjusted hazard ratio 

397 

 

57.6 

49.1-72.8 

0.61 

393 

 

44.0 

34.4-49.1 

-- 

95% CI (0.47-0.80)  -- 

p-valuea 0.0003 -- 

Progression Free Survival 

Median (months) 

95% CI 

Adjusted hazard ratio 
95% CI 

p-value* 

 

19.8 

16.7-22.8 

0.60 

0.51-0.72 

P<0.0001 

 

11.6 

10.8-14.3 

-- 

-- 

-- 

PSA response** at 6 months – N(%) 

p-valuea* 

127 (32.0) 

<0.0001 

77 (19.6) 

-- 

PSA response** at 12 months – N(%) 

p-valuea* 

110 (27.7) 

<0.0001 

66 (16.8) 

-- 

Time to castration-resistant prostate cancerb   

Median (months)  

95% CI 

Adjusted hazard ratio 

20.2 

(17.2-23.6) 

0.61 

11.7 

(10.8-14.7) 

-- 

95% CI (0.51-0.72) -- 

p-valuea* <0.0001 -- 

Time to clinical progressionc    

Median (months)  33.0 19.8 

95% CI (27.3-41.2) (17.9-22.8) 

Adjusted hazard ratio 0.61 -- 

95% CI (0.50-0.75) -- 

p-valuea* <0.0001 -- 



174 

Endpoint 

 

Docetaxel +ADT  

 

ADT alone 

a Time to event variables: Stratified log-rank test.  

  Response rate variables: Fisher's Exact test  

* p-value for descriptive purpose. 

** PSA response: Prostate-Specific Antigen response: PSA level <0.2 ng/mL measured for two 

consecutive measurements at least 4 weeks apart. 

b Time to castration-resistant prostate cancer = time from randomization to PSA progression or 

clinical progression (i.e., increasing symptomatic bone metastases, progression per Response 

Evaluation Criteria in Solid Tumours (RECIST) criteria, or clinical deterioration due to cancer 

per the Investigator’s opinion), whichever occurred first. 
c The time to clinical progression = the time from randomization until clinical progression (i.e., 

increased symptoms of bone metastases; progression according to RECIST; or clinical deterioration 

due to cancer according to the investigator’s opinion). 

 

Gastric adenocarcinoma 

 

A multi-centre, open-label, randomised study, was conducted to evaluate the safety and efficacy of 

docetaxel for the treatment of patients with metastatic gastric adenocarcinoma, including 

adenocarcinoma of the gastroesophageal junction, who had not received prior chemotherapy for 

metastatic disease. A total of 445 patients with KPS > 70 were treated with either docetaxel (T) 

(75 mg/m2 on day 1) in combination with cisplatin (C) (75 mg/m2 on day 1) and 5-fluorouracil (F) 

(750 mg/m2 per day for 5 days) or cisplatin (100 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2 per 

day for 5 days). The length of a treatment cycle was 3 weeks for the TCF arm and 4 weeks for the CF 

arm. The median number of cycles administered per patient was 6 (with a range of 1-16) for the TCF 

arm compared to 4 (with a range of 1-12) for the CF arm. Time to progression (TTP) was the primary 

endpoint. The risk reduction of progression was 32.1% and was associated with a significantly longer 

TTP (p = 0.0004) in favour of the TCF arm. Overall survival was also significantly longer 

(p = 0.0201) in favour of the TCF arm with a risk reduction of mortality of 22.7%. Efficacy results are 

summarized in the following table: 

 

Efficacy of docetaxel in the treatment of patients with gastric adenocarcinoma 

 

Endpoint TCF 

n = 221 

CF 

n = 224 

Median TTP (months) 

(95% CI) 

Hazard ratio 

(95% CI) 

*p-value 

5.6 

(4.86-5.91) 

3.7 

(3.45-4.47) 

1.473 

(1.189-1.825) 

0.0004 

Median survival (months) 

(95% CI) 

2-year estimate (%) 

Hazard ratio 

(95% CI) 

*p-value 

9.2 

(8.38-10.58) 

18.4 

8.6 

(7.16-9.46) 

8.8 

1.293 

(1.041-1.606) 

0.0201 

Overall Response Rate (CR+PR) (%) 

p-value 

36.7 25.4 

0.0106 

Progressive Disease as Best Overall Response (%) 16.7 25.9 

*Unstratified logrank test  



175 

 

Subgroup analyses across age, gender and race consistently favoured the TCF arm compared to the CF 

arm.  

 

A survival update analysis conducted with a median follow-up time of 41.6 months no longer showed 

a statistically significant difference although always in favour of the TCF regimen and showed that the 

benefit of TCF over CF is clearly observed between 18 and 30 months of follow up.  

 

Overall, quality of life (QoL) and clinical benefit results consistently indicated improvement in favour 

of the TCF arm. Patients treated with TCF had a longer time to 5% definitive deterioration of global 

health status on the QLQ-C30 questionnaire (p = 0.0121) and a longer time to definitive worsening of 

Karnofsky performance status (p = 0.0088) compared to patients treated with CF. 

 

Head and neck cancer 

 

• Induction chemotherapy followed by radiotherapy (TAX323)  
The safety and efficacy of docetaxel in the induction treatment of patients with squamous cell 

carcinoma of the head and neck (SCCHN) was evaluated in a phase III, multi-centre, open-label, 

randomised study (TAX323). In this study, 358 patients with inoperable locally advanced SCCHN, 

and WHO performance status 0 or 1, were randomised to one of two treatment arms. Patients on the 

docetaxel arm received docetaxel (T) 75 mg/m2 followed by cisplatin (P) 75 mg/m2 followed by 

5-fluorouracil (F) 750 mg/m2 per day as a continuous infusion for 5 days. This regimen was 

administered every three weeks for 4 cycles in case at least a minor response (≥ 25% reduction in 

bidimensionally measured tumour size) was observed after 2 cycles. At the end of chemotherapy, with 

a minimal interval of 4 weeks and a maximal interval of 7 weeks, patients whose disease did not 

progress received radiotherapy (RT) according to institutional guidelines for 7 weeks (TPF/RT). 

Patients on the comparator arm received cisplatin (P) 100 mg/m2 followed by 5-fluorouracil (F) 

1000 mg/m2 per day for 5 days. This regimen was administered every three weeks for 4 cycles in case 

at least a minor response (≥ 25% reduction in bidimensionally measured tumour size) was observed 

after 2 cycles. At the end of chemotherapy, with a minimal interval of 4 weeks and a maximal interval 

of 7 weeks, patients whose disease did not progress received radiotherapy (RT) according to 

institutional guidelines for 7 weeks (PF/RT). Locoregional therapy with radiation was delivered either 

with a conventional fraction (1.8 Gy - 2.0 Gy once a day, 5 days per week for a total dose of 66 to 

70 Gy), or accelerated/hyperfractionated regimens of radiation therapy (twice a day, with a minimum 

interfraction interval of 6 hours, 5 days per week). A total of 70 Gy was recommended for accelerated 

regimens and 74 Gy for hyperfractionated schemes. Surgical resection was allowed following 

chemotherapy, before or after radiotherapy. Patients on the TPF arm received antibiotic prophylaxis 

with ciprofloxacin 500 mg orally twice daily for 10 days starting on day 5 of each cycle, or equivalent. 

The primary endpoint in this study, progression-free survival (PFS), was significantly longer in the 

TPF arm compared to the PF arm, p = 0.0042 (median PFS: 11.4 vs. 8.3 months respectively) with an 

overall median follow up time of 33.7 months. Median overall survival was also significantly longer in 

favour of the TPF arm compared to the PF arm (median OS: 18.6 vs. 14.5 months respectively) with a 

28% risk reduction of mortality, p = 0.0128. Efficacy results are presented in the table below:  

 

Efficacy of docetaxel in the induction treatment of patients with inoperable locally advanced SCCHN 

(Intent-to-Treat Analysis) 

 

Endpoint Docetaxel + 

Cis + 5-FU 

n = 177 

Cis + 5-FU 

 

n = 181 

Median progression free survival (months) 

(95% CI) 

Adjusted Hazard ratio 

(95% CI) 

*p-value 

11.4 

(10.1-14.0) 

8.3 

(7.4-9.1) 

0.70 

(0.55-0.89) 

0.0042 



176 

Endpoint Docetaxel + 

Cis + 5-FU 

n = 177 

Cis + 5-FU 

 

n = 181 

Median survival (months) 

(95% CI) 

Hazard ratio 

(95% CI) 

**p-value 

18.6 

(15.7-24.0) 

14.5 

(11.6-18.7) 

0.72 

(0.56-0.93) 

0.0128 

Best overall response to chemotherapy (%) 

(95% CI)  

***p-value 

67.8 

(60.4-74.6) 

53.6 

(46.0-61.0) 

0.006 

Best overall response to study treatment [chemotherapy 

+/- radiotherapy] (%) 

(95% CI)  

***p-value 

72.3 

(65.1-78.8) 

58.6 

(51.0-65.8) 

0.006 

 Median duration of response to chemotherapy ± 

radiotherapy (months) 

(95% CI)  

Hazard ratio 

(95% CI) 

**p-value 

n = 128 

15.7 

(13.4-24.6) 

n = 106 

11.7 

(10.2-17.4) 

0.72 

(0.52-0.99) 

0.0457 

A hazard ratio of less than 1 favours docetaxel + cisplatin + 5-FU 

*Cox model (adjustment for Primary tumour site, T and N clinical stages and PSWHO) 

**Logrank test  

*** Chi-square test  

 

Quality of life parameters 

 

Patients treated with TPF experienced significantly less deterioration of their Global health score 

compared to those treated with PF (p = 0.01, using the EORTC QLQ-C30 scale). 

 

Clinical benefit parameters 

 

The performance status scale, for head and neck (PSS-HN) subscales designed to measure 

understandability of speech, ability to eat in public, and normalcy of diet, was significantly in favour 

of TPF as compared to PF. 

Median time to first deterioration of WHO performance status was significantly longer in the TPF arm 

compared to PF. Pain intensity score improved during treatment in both groups indicating adequate 

pain management.  

 

• Induction chemotherapy followed by chemoradiotherapy (TAX324)  
The safety and efficacy of docetaxel in the induction treatment of patients with locally advanced 

squamous cell carcinoma of the head and neck (SCCHN) was evaluated in a randomised, multi-centre 

open-label, phase III, study (TAX324). In this study, 501 patients, with locally advanced SCCHN, and 

a WHO performance status of 0 or 1, were randomised to one of two arms. The study population 

comprised patients with technically unresectable disease, patients with low probability of surgical cure 

and patients aiming at organ preservation. The efficacy and safety evaluation solely addressed survival 

endpoints and the success of organ preservation was not formally addressed. Patients on the docetaxel 

arm received docetaxel (T) 75 mg/m² by intravenous infusion on day 1 followed by cisplatin (P) 

100 mg/m² administered as a 30-minute to three-hour intravenous infusion, followed by the continuous 

intravenous infusion of 5-fluorouracil (F) 1000 mg/m²/day from day 1 to day 4. The cycles were 

repeated every 3 weeks for 3 cycles. All patients who did not have progressive disease were to receive 

chemoradiotherapy (CRT) as per protocol (TPF/CRT). Patients on the comparator arm received 



177 

cisplatin (P) 100 mg/m² as a 30-minute to three-hour intravenous infusion on day 1 followed by the 

continuous intravenous infusion of 5-fluorouracil (F) 1000 mg/m²/day from day 1 to day 5. The cycles 

were repeated every 3 weeks for 3 cycles. All patients who did not have progressive disease were to 

receive CRT as per protocol (PF/CRT).  

Patients in both treatment arms were to receive 7 weeks of CRT following induction chemotherapy 

with a minimum interval of 3 weeks and no later than 8 weeks after start of the last cycle (day 22 to 

day 56 of last cycle). During radiotherapy, carboplatin (AUC 1.5) was given weekly as a one-hour 

intravenous infusion for a maximum of 7 doses. Radiation was delivered with megavoltage equipment 

using once daily fractionation (2 Gy per day, 5 days per week for 7 weeks, for a total dose of 

70-72 Gy). Surgery on the primary site of disease and/or neck could be considered at anytime 

following completion of CRT. All patients on the docetaxel-containing arm of the study received 

prophylactic antibiotics. The primary efficacy endpoint in this study, overall survival (OS) was 

significantly longer (log-rank test, p = 0.0058) with the docetaxel-containing regimen compared to PF 

(median OS: 70.6 versus 30.1 months respectively), with a 30% risk reduction in mortality compared 

to PF (hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.54-0.90) with an overall median 

follow up time of 41.9 months. The secondary endpoint, PFS, demonstrated a 29% risk reduction of 

progression or death and a 22 month improvement in median PFS (35.5 months for TPF and 13.1 for 

PF). This was also statistically significant with an HR of 0.71; 95% CI 0.56-0.90; log-rank test 

p = 0.004. Efficacy results are presented in the table below: 

 

Efficacy of docetaxel in the induction treatment of patients with locally advanced SCCHN (Intent-to-

Treat Analysis) 

 

Endpoint Docetaxel + Cis + 5-FU 

n = 255 

Cis + 5-FU 

n = 246 

Median overall survival (months) 

(95% CI) 

Hazard ratio: 

(95% CI) 

*p-value  

70.6 

(49.0-NA) 

30.1 

(20.9-51.5) 

0.70 

(0.54-0.90) 

0.0058 

Median PFS (months) 

(95% CI) 

Hazard ratio: 

(95% CI) 

**p-value  

35.5 

(19.3-NA) 

13.1 

(10.6-20.2) 

0.71 

(0.56 - 0.90) 

0.004 

Best overall response (CR + PR) to 

chemotherapy (%) 

(95% CI)  

***p-value 

71.8 

(65.8-77.2) 

64.2 

(57.9-70.2) 

0.070 

Best overall response (CR + PR) to study 

treatment [chemotherapy +/- 

chemoradiotherapy] (%) 

(95% CI) 

***p-value 

 

76.5 

(70.8-81.5) 

 

71.5 

(65.5-77.1) 

0.209 

A hazard ratio of less than 1 favours docetaxel + cisplatin + fluorouracil  

*un-adjusted log-rank test  

**un-adjusted log-rank test, not adjusted for multiple comparisons  

***Chi square test, not adjusted for multiple comparisons  

NA-not applicable 

 

 

 

 



178 

5.2 Pharmacokinetic properties 

 

Absorption 

 

The pharmacokinetics of docetaxel have been evaluated in cancer patients after administration of 20-

115 mg/m2 in phase I studies. The kinetic profile of docetaxel is dose independent and consistent with 

a three-compartment pharmacokinetic model with half lives for the α, β and γ phases of 4 min, 36 min 

and 11.1 h, respectively. The late phase is due, in part, to a relatively slow efflux of docetaxel from the 

peripheral compartment. 

 

Distribution 

 

Following the administration of a 100 mg/m2 dose given as a one-hour infusion a mean peak plasma 

level of 3.7 μg/ml was obtained with a corresponding AUC of 4.6 h.μg/ml. Mean values for total body 

clearance and steady-state volume of distribution were 21 l/h/m2 and 113 l, respectively. Inter 

individual variation in total body clearance was approximately 50%. Docetaxel is more than 95% 

bound to plasma proteins. 

 

Elimination 

 

A study of 14C-docetaxel has been conducted in three cancer patients. Docetaxel was eliminated in 

both the urine and faeces following cytochrome P450-mediated oxidative metabolism of the tert-butyl 

ester group, within seven days, the urinary and faecal excretion accounted for about 6% and 75% of 

the administered radioactivity, respectively. About 80% of the radioactivity recovered in faeces is 

excreted during the first 48 hours as one major inactive metabolite and 3 minor inactive metabolites 

and very low amounts of unchanged medicinal product.  

 

Special populations 

 

Age and gender 

A population pharmacokinetic analysis has been performed with docetaxel in 577 patients. 

Pharmacokinetic parameters estimated by the model were very close to those estimated from phase I 

studies. The pharmacokinetics of docetaxel were not altered by the age or sex of the patient. 

 

Hepatic impairment 

In a small number of patients (n = 23) with clinical chemistry data suggestive of mild to moderate liver 

function impairment (ALT, AST ≥ 1.5 times the ULN associated with alkaline phosphatase ≥ 2.5 

times the ULN), total clearance was lowered by 27% on average (see section 4.2). 

 

Fluid retention 

Docetaxel clearance was not modified in patients with mild to moderate fluid retention and there are 

no data available in patients with severe fluid retention. 

 

Combination therapy 

 

Doxorubicin 

When used in combination, docetaxel does not influence the clearance of doxorubicin and the plasma 

levels of doxorubicinol (a doxorubicin metabolite). The pharmacokinetics of docetaxel, doxorubicin 

and cyclophosphamide were not influenced by their co-administration.  

 

Capecitabine 

Phase I study evaluating the effect of capecitabine on the pharmacokinetics of docetaxel and vice versa 

showed no effect by capecitabine on the pharmacokinetics of docetaxel (Cmax and AUC) and no 

effect by docetaxel on the pharmacokinetics of a relevant capecitabine metabolite 5'-DFUR.  

 

 

 



179 

Cisplatin 

Clearance of docetaxel in combination therapy with cisplatin was similar to that observed following 

monotherapy. The pharmacokinetic profile of cisplatin administered shortly after docetaxel infusion is 

similar to that observed with cisplatin alone.  

 

Cisplatin and 5-fluorouracil 

The combined administration of docetaxel, cisplatin and 5-fluorouracil in 12 patients with solid 

tumours had no influence on the pharmacokinetics of each individual medicinal product.  

 

Prednisone and dexamethasone 

The effect of prednisone on the pharmacokinetics of docetaxel administered with standard 

dexamethasone premedication has been studied in 42 patients. 

 

Prednisone 

No effect of prednisone on the pharmacokinetics of docetaxel was observed. 

 

 

5.3  Preclinical safety data 

 

The carcinogenic potential of docetaxel has not been studied. 

 

Docetaxel has been shown to be mutagenic in the in vitro micronucleus and chromosome aberration 

test in CHO-K1 cells and in the in vivo micronucleus test in the mouse. However, it did not induce 

mutagenicity in the Ames test or the CHO/HGPRT gene mutation assay. These results are consistent 

with the pharmacological activity of docetaxel.  

 

It was shown that docetaxel was embryotoxic and fetotoxic in rats and rabbits. Undesirable effects on 

the testis observed in rodent toxicity studies suggest that docetaxel may impair male fertility. 

 

 

6. PHARMACEUTICAL PARTICULARS 
 

6.1 List of excipients 

 

Polysorbate 80 

Ethanol anhydrous 

Anhydrous citric acid (pH adjustment) 

 

 

6.2 Incompatibilities 

 

This medicinal product must not be mixed with other medicinal products except those mentioned in 

section 6.6. 

 

 

6.3 Shelf life 

 

Unopened vial 

2 years. 

 

After opening of the vial 

Each vial is for single use and should be used immediately after opening. If not used immediately, 

in-use storage times and conditions are the responsibility of the user. 

 

Once added to the infusion bag 



180 

From a microbiological point of view, reconstitution/dilution must take place in controlled and aseptic 

conditions and the medicinal product should be used immediately. If not used immediately, in-use 

storage times and conditions are the responsibility of the user. 

 

Once added as recommended into the infusion bag, the docetaxel infusion solution, if stored below 

25°C, is stable for 6 hours. It should be used within 6 hours (including the one hour infusion 

intravenous administration). 

 

In addition, physical and chemical in-use stability of the infusion solution prepared as recommended 

has been demonstrated in non-PVC bags up to 48 hours when stored between 2 to 8°C. 

 

 

6.4 Special precautions for storage 

 

Do not store above 25°C.  

Store in the original package in order to protect from light.  

 

For storage conditions of the diluted medicinal product, see section 6.3. 

 

 

6.5 Nature and contents of container 

 

10 ml clear, colourless Type-I glass vial, closed with flurotec rubber stopper and a yellow flip-off 

aluminium over seal containing 8 ml of concentrate. 

 

Each box contains one vial. 

 

 

6.6 Special precautions for disposal and other handling 

 

DOCETAXEL KABI is an antineoplastic agent and, as with other potentially toxic compounds, 

caution should be exercised when handling it and preparing the solution. The use of gloves is 

recommended. 

 

If DOCETAXEL KABI concentrate or infusion solution should come into contact with skin, wash 

immediately and thoroughly with soap and water. If DOCETAXEL KABI concentrate or infusion 

solution should come into contact with mucous membranes, wash immediately and thoroughly with 

water. 

 

Preparation for the intravenous administration 

 

Preparation of the infusion solution 

DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 

with this medicinal product (DOCETAXEL KABI 160 mg/8 ml concentrate for solution for 

infusion, which contains only 1 vial). 

 

DOCETAXEL KABI 160 mg/8 ml concentrate for solution for infusion requires NO prior 

dilution with a solvent and is ready to add to the infusion solution. 

 

Each vial is for single use and should be used immediately. 

 

If the vials are stored under refrigeration, allow the required number of boxes of DOCETAXEL KABI 

concentrate for solution for infusion to stand below 25°C for 5 minutes before use. More than one vial 

of DOCETAXEL KABI concentrate for solution for infusion may be necessary to obtain the required 

dose for the patient. Aseptically withdraw the required amount of DOCETAXEL KABI concentrate 

for solution for infusion using a calibrated syringe.  

In DOCETAXEL KABI 160 mg/8 ml vial the concentration of docetaxel is 20 mg/ml. 



181 

The required volume of DOCETAXEL KABI concentrate for solution for infusion must be injected 

via a single injection (one shot) into a 250 ml infusion bag or bottle containing either 5% glucose 

solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. 

 

If a dose greater than 190 mg of docetaxel is required, use a larger volume of the infusion vehicle so 

that a concentration of 0.74 mg/ml docetaxel is not exceeded. 

 

Mix the infusion bag or bottle manually using a rocking motion. 

 

The infusion bag solution should be used within 6 hours below 25°C including the one hour infusion 

to the patient. 

 

As with all parenteral products, DOCETAXEL KABI infusion solution should be visually inspected 

prior to use, and solutions containing a precipitate should be discarded. 

 

Docetaxel infusion solution is supersaturated, therefore may crystallize over time. If crystals appear, 

the solution must no longer be used and shall be discarded. 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Fresenius Kabi Deutschland GmbH 

Else-Kröner-Straße 1, 

61352 Bad Homburg v.d.Höhe 

Germany 

 

 

8. MARKETING AUTHORISATION NUMBER 
 

EU/1/12/770/003 

 

 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 22nd May 2012 

Date of latest renewal: 23 February 2017 

 

 

10. DATE OF REVISION OF THE TEXT 
 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu  



182 

1. NAME OF THE MEDICINAL PRODUCT 
 

DOCETAXEL KABI 180 mg/9 ml concentrate for solution for infusion 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each ml of concentrate contains 20 mg docetaxel anhydrous. 

 

One vial of 9 ml of concentrate contains 180 mg of docetaxel. 

 

Excipient with known effect 

Each vial of concentrate contains 4.5 ml of ethanol anhydrous (3.55 g). 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Concentrate for solution for infusion (sterile concentrate). 

 

The concentrate is a clear, colourless to pale yellow solution. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 

 

Breast cancer 

 

DOCETAXEL KABI in combination with doxorubicin and cyclophosphamide is indicated for the 

adjuvant treatment of patients with: 

• operable node-positive breast cancer 

• operable node-negative breast cancer. 
 

For patients with operable node-negative breast cancer, adjuvant treatment should be restricted to 

patients eligible to receive chemotherapy according to internationally established criteria for primary 

therapy of early breast cancer (see section 5.1). 

DOCETAXEL KABI in combination with doxorubicin is indicated for the treatment of patients with 

locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for 

this condition. 

 

DOCETAXEL KABI monotherapy is indicated for the treatment of patients with locally advanced or 

metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have 

included an anthracycline or an alkylating agent. 

 

DOCETAXEL KABI in combination with trastuzumab is indicated for the treatment of patients with 

metastatic breast cancer whose tumours over express HER2 and who previously have not received 

chemotherapy for metastatic disease. 

 

DOCETAXEL KABI in combination with capecitabine is indicated for the treatment of patients with 

locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy 

should have included an anthracycline. 



183 

Non-small cell lung cancer 

 

DOCETAXEL KABI is indicated for the treatment of patients with locally advanced or metastatic 

non-small cell lung cancer after failure of prior chemotherapy. 

 

DOCETAXEL KABI in combination with cisplatin is indicated for the treatment of patients with 

unresectable, locally advanced or metastatic non-small cell lung cancer, in patients who have not 

previously received chemotherapy for this condition. 

 

Prostate cancer 

 

DOCETAXEL KABI in combination with prednisone or prednisolone is indicated for the treatment of 

patients with castration-resistant metastatic prostate cancer. 

 

DOCETAXEL KABI in combination with androgen-deprivation therapy (ADT), with or without 

prednisone or prednisolone, is indicated for the treatment of patients with metastatic hormone-

sensitive prostate cancer. 

 

Gastric adenocarcinoma 

 

DOCETAXEL KABI in combination with cisplatin and 5-fluorouracil is indicated for the treatment of 

patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal 

junction, who have not received prior chemotherapy for metastatic disease. 

 

Head and neck cancer 

 

DOCETAXEL KABI in combination with cisplatin and 5-fluorouracil is indicated for the induction 

treatment of patients with locally advanced squamous cell carcinoma of the head and neck. 

 

 

4.2 Posology and method of administration 

 

The use of docetaxel should be confined to units specialised in the administration of cytotoxic 

chemotherapy and it should only be administered under the supervision of a physician qualified in the 

use of anticancer chemotherapy (see section 6.6). 

 

Posolgy 

 

For breast, non-small cell lung, gastric, and head and neck cancers, premedication consisting of an oral 

corticosteroid, such as dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to 

docetaxel administration, unless contraindicated, can be used (see section 4.4).  

For metastatic castration-resistant prostate cancer, given the concurrent use of prednisone or 

prednisolone the recommended premedication regimen is oral dexamethasone 8 mg, 12 hours, 3 hours 

and 1 hour before the docetaxel infusion (see section 4.4). 

For metastatic hormone-sensitive prostate cancer, irrespective of the concurrent use of prednisone or 

prednisolone, the recommended premedication regimen is oral dexamethasone 8 mg 12 hours, 3 hours, 

and 1 hour before docetaxel infusion (see section 4.4). 

 

Prophylactic G-CSF may be used to mitigate the risk of haematological toxicities. 

 

Docetaxel is administered as a one-hour infusion every three weeks.  

 

Breast cancer 

In the adjuvant treatment of operable node-positive and node-negative breast cancer, the recommended 

dose of docetaxel is 75 mg/m2 administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 

500 mg/m2 every 3 weeks for 6 cycles (TAC regimen) (see also Dose adjustments during treatment). 

For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose 



184 

of docetaxel is 100 mg/m2 in monotherapy. In first-line treatment, docetaxel 75 mg/m2 is given in 

combination therapy with doxorubicin (50 mg/m2). 

 

In combination with trastuzumab the recommended dose of docetaxel is 100 mg/m2 every three weeks, 

with trastuzumab administered weekly. In the pivotal study the initial docetaxel infusion was started 

the day following the first dose of trastuzumab. The subsequent docetaxel doses were administered 

immediately after completion of the trastuzumab infusion, if the preceding dose of trastuzumab was 

well tolerated. For trastuzumab dose and administration, see trastuzumab summary of product 

characteristics.  

 

In combination with capecitabine, the recommended dose of docetaxel is 75 mg/m2 every three weeks, 

combined with capecitabine at 1250 mg/m2 twice daily (within 30 minutes after a meal) for 2 weeks 

followed by 1-week rest period. For capecitabine dose calculation according to body surface area, see 

capecitabine summary of product characteristics.  

 

Non-small cell lung cancer 

In chemotherapy naïve patients treated for non-small cell lung cancer, the recommended dose regimen 

is docetaxel 75 mg/m2 immediately followed by cisplatin 75 mg/m2 over 30-60 minutes. For treatment 

after failure of prior platinum-based chemotherapy, the recommended dose is 75 mg/m² as a single 

agent. 

 

Prostate cancer 

Prostate cancer Metastatic castration-resistant prostate cancer  
The recommended dose of docetaxel is 75 mg/m2. Prednisone or prednisolone 5 mg orally twice daily 

is administered continuously (see section 5.1). 

 

Metastatic hormone-sensitive prostate cancer 

The recommended dose of docetaxel is 75 mg/m2 every 3 weeks for 6 cycles. Prednisone or 

prednisolone 5 mg orally twice daily may be administered continuously. 

 

Gastric adenocarcinoma 

The recommended dose of docetaxel is 75 mg/m2 as a 1-hour infusion, followed by cisplatin 

75 mg/m2, as a 1- to 3- hour infusion (both on day 1 only), followed by 5-fluorouracil 750 mg/m2 per 

day given as a 24-hour continuous infusion for 5 days, starting at the end of the cisplatin infusion. 

Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and 

appropriate hydration for cisplatin administration. Prophylactic G-CSF should be used to mitigate the 

risk of haematological toxicities (see also Dose adjustments during treatment). 

 

Head and neck cancer 

Patients must receive premedication with antiemetics and appropriate hydration (prior to and after 

cisplatin administration). Prophylactic G-CSF may be used to mitigate the risk of haematological 

toxicities. All patients on the docetaxel-containing arm of the TAX 323 and TAX 324 studies, received 

prophylactic antibiotics. 

 

• Induction chemotherapy followed by radiotherapy (TAX 323) 
For the induction treatment of inoperable locally advanced squamous cell carcinoma of the head 

and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m2 as a 1 hour infusion 

followed by cisplatin 75 mg/m2 over 1 hour, on day one, followed by 5-fluorouracil as a 

continuous infusion at 750 mg/m2 per day for five days. This regimen is administered every 

3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy. 

 

• Induction chemotherapy followed by chemoradiotherapy (TAX 324) 
For the induction treatment of patients with locally advanced (technically unresectable, low 

probability of surgical cure, and aiming at organ preservation) squamous cell carcinoma of the 

head and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m2 as a 1 hour 

intravenous infusion on day 1, followed by cisplatin 100 mg/m2 administered as a 30-minute to 

3-hour infusion, followed by 5-fluorouracil 1000 mg/m2/day as a continuous infusion from day 1 



185 

to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, 

patients should receive chemoradiotherapy. 

 

For cisplatin and 5-fluorouracil dose modifications, see the corresponding summary of product 

characteristics. 

 

Dose adjustments during treatment 

 

General 

Docetaxel should be administered when the neutrophil count is ≥ 1,500 cells/mm3. 

In patients who experienced either febrile neutropenia, neutrophil count < 500 cells/mm3 for more than 

one week, severe or cumulative cutaneous reactions or severe peripheral neuropathy during docetaxel 

therapy, the dose of docetaxel should be reduced from 100 mg/m2 to 75 mg/m2 and/or from 75 to 

60 mg/m². If the patient continues to experience these reactions at 60 mg/m², the treatment should be 

discontinued. 

 

Adjuvant therapy for breast cancer 

Primary G-CSF prophylaxis should be considered in patients who receive docetaxel, doxorubicin and 

cyclophosphamide (TAC) adjuvant therapy for breast cancer. Patients who experience febrile 

neutropenia and/or neutropenic infection should have their docetaxel dose reduced to 60 mg/m² in all 

subsequent cycles (see sections 4.4 and 4.8). Patients who experience Grade 3 or 4 stomatitis should 

have their dose decreased to 60 mg/m². 

 

In combination with cisplatin 

For patients who are dosed initially at docetaxel 75 mg/m2 in combination with cisplatin and whose 

nadir of platelet count during the previous course of therapy is < 25,000 cells/mm3, or in patients who 

experience febrile neutropenia, or in patients with serious non-haematologic toxicities, the docetaxel 

dose in subsequent cycles should be reduced to 65 mg/m2. For cisplatin dose adjustments, see the 

corresponding summary of product characteristics.  

 

In combination with capecitabine 

• For capecitabine dose modifications, see capecitabine summary of product characteristics. 

• For patients developing the first appearance of Grade 2 toxicity, which persists at the time of the 
next docetaxel/capecitabine treatment, delay treatment until resolved to Grade 0-1, and resume at 

100% of the original dose. 

• For patients developing the second appearance of Grade 2 toxicity, or the first appearance of 
Grade 3 toxicity, at any time during the treatment cycle, delay treatment until resolved to Grade 

0-1 and then resume treatment with docetaxel 55 mg/m². 

• For any subsequent appearances of toxicities, or any Grade 4 toxicities, discontinue the docetaxel 
dose. 

 

For trastuzumab dose modifications, see trastuzumab summary of product characteristics. 

 

In combination with cisplatin and 5-fluorouracil 

If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite 

G-CSF use, the docetaxel dose should be reduced from 75 to 60 mg/m2. If subsequent episodes of 

complicated neutropenia occur the docetaxel dose should be reduced from 60 to 45 mg/m2. In case of 

Grade 4 thrombocytopenia the docetaxel dose should be reduced from 75 to 60 mg/m2. Patients should 

not be retreated with subsequent cycles of docetaxel until neutrophils recover to a level 

>1,500 cells/mm3 and platelets recover to a level >100,000 cells/mm3. Discontinue treatment if these 

toxicities persist (see section 4.4). 

Recommended dose modifications for toxicities in patients treated with docetaxel in combination with 

cisplatin and 5-fluorouracil (5-FU): 

 

 

 



186 

Toxicity Dose adjustment 

Diarrhoea grade 3  First episode: reduce 5-FU dose by 20%. 

Second episode: then reduce docetaxel dose by 20%. 

Diarrhoea grade 4 First episode: reduce docetaxel and 5-FU doses by 20%. 

Second episode: discontinue treatment. 

Stomatitis/mucositis grade 3  First episode: reduce 5-FU dose by 20%. 

Second episode: stop 5-FU only, at all subsequent cycles. 

Third episode: reduce docetaxel dose by 20%. 

Stomatitis/mucositis grade 4 First episode: stop 5-FU only, at all subsequent cycles. 

Second episode: reduce docetaxel dose by 20%. 

 

For cisplatin and 5-fluorouracil dose adjustments, see the corresponding summary of product 

characteristics. 

 

In the pivotal SCCHN studies patients who experienced complicated neutropenia (including prolonged 

neutropenia, febrile neutropenia, or infection), it was recommended to use G-CSF to provide 

prophylactic coverage (eg, day 6-15) in all subsequent cycles. 

 

Special populations 

 

Patients with hepatic impairment 

Based on pharmacokinetic data with docetaxel at 100 mg/m² as single agent, patients who have both 

elevations of transaminase (ALT and/or AST) greater than 1.5 times the upper limit of the normal 

range (ULN) and alkaline phosphatase greater than 2.5 times the ULN, the recommended dose of 

docetaxel is 75 mg/m2 (see sections 4.4 and 5.2). For those patients with serum bilirubin > ULN and/or 

ALT and AST > 3.5 times the ULN associated with alkaline phosphatase > 6 times the ULN, no 

dose-reduction can be recommended and docetaxel should not be used unless strictly indicated. 

In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric 

adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST > 1.5 × ULN 

associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no 

dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No 

data are available in patients with hepatic impairment treated by docetaxel in combination in the other 

indications.  

 

Paediatric population 

The safety and efficacy of DOCETAXEL KABI in nasopharyngeal carcinoma in children aged 

1 month to less than 18 years have not yet been established. 

There is no relevant use of DOCETAXEL KABI in the paediatric population in the indications breast 

cancer, non-small cell lung cancer, prostate cancer, gastric carcinoma and head and neck cancer, not 

including type II and III less differentiated nasopharyngeal carcinoma. 

 

Elderly 

Based on a population pharmacokinetic analysis, there are no special instructions for use in the elderly 

In combination with capecitabine, for patients 60 years of age or more, a starting dose reduction of 

capecitabine to 75% is recommended (see capecitabine summary of product characteristics). 

 

Method of administration 

For instructions on preparation and administration of the product, see section 6.6. 

 

 

4.3 Contraindications 

 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 



187 

Patients with baseline neutrophil count of < 1,500 cells/mm3. 

 

Patients with severe liver impairment (see sections 4.2 and 4.4). 

 

Contraindications for other medicinal products also apply, when combined with docetaxel. 

 

 

4.4 Special warnings and precautions for use 

 

For breast and non-small cell lung cancers, premedication consisting of an oral corticosteroid, such as 

dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to docetaxel 

administration, unless contraindicated, can reduce the incidence and severity of fluid retention as well 

as the severity of hypersensitivity reactions. For prostate cancer, the premedication is oral 

dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the docetaxel infusion (see section 4.2). 

 

Haematology 

 

Neutropenia is the most frequent adverse reaction of docetaxel. Neutrophil nadirs occurred at a median 

of 7 days but this interval may be shorter in heavily pre-treated patients. Frequent monitoring of 

complete blood counts should be conducted on all patients receiving docetaxel. Patients should be 

retreated with docetaxel when neutrophils recover to a level ≥ 1,500 cells/mm3 (see section 4.2). 

 

In the case of severe neutropenia (< 500 cells/mm3 for seven days or more) during a course of 

docetaxel therapy, a reduction in dose for subsequent courses of therapy or the use of appropriate 

symptomatic measures are recommended (see section 4.2). 

 

In patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (TCF), febrile 

neutropenia and neutropenic infection occurred at lower rates when patients received prophylactic 

G-CSF. Patients treated with TCF should receive prophylactic G-CSF to mitigate the risk of 

complicated neutropenia (febrile neutropenia, prolonged neutropenia or neutropenic infection). 

Patients receiving TCF should be closely monitored (see sections 4.2 and 4.8). 

 

In patients treated with docetaxel in combination with doxorubicin and cyclophosphamide (TAC), 

febrile neutropenia and/or neutropenic infection occurred at lower rates when patients received 

primary G-CSF prophylaxis. Primary G-CSF prophylaxis should be considered in patients who receive 

adjuvant therapy with TAC for breast cancer to mitigate the risk of complicated neutropenia (febrile 

neutropenia, prolonged neutropenia or neutropenic infection). Patients receiving TAC should be 

closely monitored (see sections 4.2 and 4.8). 

 

Gastrointestinal reactions 

 

Caution is recommended for patients with neutropenia, particularly at risk for developing 

gastrointestinal complications. Although majority of cases occurred during the first or second cycle of 

docetaxel containing regimen, enterocolitis could develop at any time, and could lead to death as early 

as on the first day of onset. Patients should be closely monitored for early manifestations of serious 

gastrointestinal toxicity (see sections 4.2, 4.4 Haematology, and 4.8). 

 

Hypersensitivity reactions 

 

Patients should be observed closely for hypersensitivity reactions especially during the first and 

second infusions. Hypersensitivity reactions may occur within a few minutes following the initiation 

of the infusion of docetaxel, thus facilities for the treatment of hypotension and bronchospasm should 

be available. If hypersensitivity reactions occur, minor symptoms such as flushing or localised 

cutaneous reactions do not require interruption of therapy. However, severe reactions, such as severe 

hypotension, bronchospasm or generalised rash/erythema require immediate discontinuation of 

docetaxel and appropriate therapy. Patients who have developed severe hypersensitivity reactions 

should not be re-challenged with docetaxel. Patients who have previously experienced a 



188 

hypersensitivity reaction to paclitaxel may be at risk to develop hypersensitivity reaction to docetaxel, 

including more severe hypersensitivity reaction. These patients should be closely monitored during 

initiation of docetaxel therapy. 

 

Cutaneous reactions 

 

Localised skin erythema of the extremities (palms of the hands and soles of the feet) with oedema 

followed by desquamation has been observed. Severe symptoms such as eruptions followed by 

desquamation which lead to interruption or discontinuation of docetaxel treatment were reported (see 

section 4.2). 

 

Severe Cutaneous Adverse Reactions (SCARs) such as Stevens-Johnson Syndrome (SJS), Toxic 

Epidermal Necrolysis (TEN) and Acute Generalized Exanthematous Pustulosis (AGEP) have been 

reported with docetaxel treatment. Patients should be informed about the signs and symptoms of 

serious skin manifestations and closely monitored. If signs and symptoms suggestive of these reactions 

appear discontinuation of docetaxel should be considered. 

 

Fluid retention 

 

Patients with severe fluid retention such as pleural effusion, pericardial effusion and ascites should be 

monitored closely. 

 

Respiratory disorders 

 

Acute respiratory distress syndrome, interstitial pneumonia/pneumonitis, interstitial lung disease, 

pulmonary fibrosis and respiratory failure have been reported and may be associated with fatal 

outcome. Cases of radiation pneumonitis have been reported in patients receiving concomitant 

radiotherapy. 

 

If new or worsening pulmonary symptoms develop, patients should be closely monitored, promptly 

investigated, and appropriately treated. Interruption of docetaxel therapy is recommended until 

diagnosis is available. Early use of supportive care measures may help improve the condition. The 

benefit of resuming docetaxel treatment must be carefully evaluated. 

 

Patients with liver impairment 

 

In patients treated with docetaxel at 100 mg/m2 as single agent who have serum transaminase levels 

(ALT and/or AST) greater than 1.5 times the ULN concurrent with serum alkaline phosphatase levels 

greater than 2.5 times the ULN, there is a higher risk of developing severe adverse reactions such as 

toxic deaths including sepsis and gastrointestinal haemorrhage which can be fatal, febrile neutropenia, 

infections, thrombocytopenia, stomatitis and asthenia. Therefore, the recommended dose of docetaxel 

in those patients with elevated liver function test (LFTs) is 75 mg/m2 and LFTs should be measured at 

baseline and before each cycle (see section 4.2). 

For patients with serum bilirubin levels > ULN and/or ALT and AST > 3.5 times the ULN concurrent 

with serum alkaline phosphatase levels > 6 times the ULN, no dose-reduction can be recommended 

and docetaxel should not be used unless strictly indicated. 

In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric 

adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST > 1.5 × ULN 

associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no 

dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No 

data are available in patients with hepatic impairment treated by docetaxel in combination in the other 

indications.  

 

Patients with renal impairment 

 

There are no data available in patients with severely impaired renal function treated with docetaxel. 

 



189 

Nervous system 

The development of severe peripheral neurotoxicity requires a reduction of dose (see section 4.2). 

 

Cardiac toxicity 

 

Heart failure has been observed in patients receiving docetaxel in combination with trastuzumab, 

particularly following anthracycline (doxorubicin or epirubicin)-containing chemotherapy. This may 

be moderate to severe and has been associated with death (see section 4.8). 

 

When patients are candidates for treatment with docetaxel in combination with trastuzumab, they 

should undergo baseline cardiac assessment. Cardiac function should be further monitored during 

treatment (e.g. every three months) to help identify patients who may develop cardiac dysfunction. For 

more details see summary of product characteristics of trastuzumab.  

 

Ventricular arrhythmia including ventricular tachycardia (sometimes fatal) has been reported in 

patients treated with docetaxel in combination regimens including doxorubicin, 5-fluorouracil and/ or 

cyclophosphamide (see section 4.8).  

Baseline cardiac assessment is recommended.   

 

Eye disorders 
 

Cystoid macular oedema (CMO) has been reported in patients treated with docetaxel. Patients with 

impaired vision should undergo a prompt and complete ophthalmologic examination. In case CMO is 

diagnosed, docetaxel treatment should be discontinued and appropriate treatment initiated (see section 

4.8). 

 

Second primary malignancies 

 

Second primary malignancies have been reported when docetaxel was given in combination with 

anticancer treatments known to be associated with second primary malignancies.  Second primary 

malignancies (including acute myeloid leukemia, myelodysplastic syndrome and non-Hodgkin 

lymphoma) may occur several months or years after docetaxel-containing therapy. Patients should be 

monitored for second primary malignancies (see section 4.8). 

 

Others 

 

Contraceptive measures must be taken by both men and women during treatment and for men at least 

6 months after cessation of therapy (see section 4.6). 

 

The concomitant use of docetaxel with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, 

clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and 

voriconazole) should be avoided (see section 4.5). 

 

Additional cautions for use in adjuvant treatment of breast cancer 

 

Complicated neutropenia 

For patients who experience complicated neutropenia (prolonged neutropenia, febrile neutropenia or 

infection), G-CSF and dose reduction should be considered (see section 4.2). 

 

Gastrointestinal reactions 

Symptoms such as early abdominal pain and tenderness, fever, diarrhoea, with or without neutropenia, 

may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated 

promptly. 

 

 

 

 



190 

Congestive heart failure (CHF) 

Patients should be monitored for symptoms of congestive heart failure during therapy and during the 

follow up period. In patients treated with the TAC regimen for node positive breast cancer, the risk of 

CHF has been shown to be higher during the first year after treatment (see sections 4.8 and 5.1). 

 

 

Patients with 4+ nodes 

As the benefit observed in patient with 4+ nodes was not statistically significant on disease-free 

survival (DFS) and overall survival (OS), the positive benefit/risk ratio for TAC in patients with 4+ 

nodes was not fully demonstrated at the final analysis (see section 5.1). 

 

Elderly  

Cautions for use in adjuvant treatment of breast cancer 

There are limited data available in patients > 70 years of age on docetaxel use in combination with 

doxorubicin and cyclophosphamide. 

 

Cautions for use in castration-resistant prostate cancer 

Of the 333 patients treated with docetaxel every three weeks in a prostate cancer study, 209 patients 

were 65 years of age or greater and 68 patients were older than 75 years. In patients treated with 

docetaxel every three weeks, the incidence of related nail changes occurred at a rate ≥ 10% higher in 

patients who were 65 years of age or greater compared to younger patients. The incidence of related 

fever, diarrhoea, anorexia, and peripheral oedema occurred at rates ≥ 10% higher in patients who were 

75 years of age or greater versus less than 65 years. 

 

Cautions for use in hormone-sensitive prostate cancer 

Of the 545 patients treated with docetaxel every 3 weeks in a hormone-sensitive prostate cancer study 

(STAMPEDE), 296 patients were 65 years of age or older, and 48 patients were 75 years of age or 

older. More patients aged ≥65 years in the docetaxel arm reported hypersensitivity reaction, 

neutropenia, anaemia, fluid retention, dyspnea, and nail changes when compared to the patients aged 

less than 65 years. None of these increases in frequency reached 10% difference with the control arm. 

In patients who were 75 years of age or older, when compared to younger patients, neutropenia, 

anaemia, diarrhea, dyspnea and upper respiratory tract infection were reported with a greater incidence 

(at least 10% higher).  

 

Cautions for use in gastric adenocarcinoma cancer 

Among the 300 (221 patients in the phase III part of the study and 79 patients in the phase II part) 

patients treated with docetaxel in combination with cisplatin and 5-fluorouracil in the gastric cancer 

study, 74 were 65 years of age or older and 4 patients were 75 years of age or older. The incidence of 

serious adverse events was higher in older people compared to younger patients. The incidence of the 

following adverse events (all grades): lethargy, stomatitis, neutropenic infection occurred at rates 

≥ 10% higher in patients who were 65 years of age or older compared to younger patients. 

Elderly treated with TCF should be closely monitored. 

 
Excipients 

 

This medicinal product contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 3.55 g ethanol 

anhydrous per vial, equivalent to 90 ml of beer or 36 ml wine. 

Harmful for those suffering from alcoholism. 

To be taken into account in pregnant or breast-feeding women, children and high-risk groups such as 

patients with liver disease, or epilepsy. 

 

Consideration should be given to possible effects on the central nervous system. 

 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

The amount of alcohol in this medicinal product may alter the effects of other medicinal products. 



191 

 

In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant 

administration of compounds which induce, inhibit or are metabolised by (and thus may inhibit the 

enzyme competitively) cytochrome P450-3A such as ciclosporine,  ketoconazole and erythromycin. 

As a result, caution should be exercised when treating patients with these medicinal products as 

concomitant therapy since there is a potential for a significant interaction. 

In case of combination with CYP3A4 inhibitors, the occurrence of docetaxel adverse reactions may 

increase, as a result of reduced metabolism. If the concomitant use of a strong CYP3A4 inhibitor (e.g., 

ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, 

telithromycin and voriconazole) cannot be avoided, a close clinical surveillance is warranted and a 

dose-adjustment of docetaxel may be suitable during the treatment with the strong CYP3A4 inhibitor 

(see section 4.4). In a pharmacokinetic study with 7 patients, the co-administration of docetaxel with 

the strong CYP3A4 inhibitor ketoconazole leads to a significant decrease in docetaxel clearance by 

49%. 

Docetaxel pharmacokinetics in the presence of prednisone was studied in patients with metastatic 

prostate cancer. Docetaxel is metabolised by CYP3A4 and prednisone is known to induce CYP3A4. 

No statistically significant effect of prednisone on the pharmacokinetics of docetaxel was observed. 

 

Docetaxel is highly protein bound (> 95%). Although the possible in vivo interaction of docetaxel with 

concomitantly administered medicinal product has not been investigated formally, in vitro interactions 

with tightly protein-bound agents such as erythromycin, diphenhydramine, propranolol, propafenone, 

phenytoin, salicylate, sulfamethoxazole and sodium valproate did not affect protein binding of 

docetaxel. In addition, dexamethasone did not affect protein binding of docetaxel. Docetaxel did not 

influence the binding of digitoxin. 

 

The pharmacokinetics of docetaxel, doxorubicin and cyclophosphamide were not influenced by their 

co-administration. Limited data from a single uncontrolled study were suggestive of an interaction 

between docetaxel and carboplatin. When combined to docetaxel, the clearance of carboplatin was 

about 50% higher than values previously reported for carboplatin monotherapy. 

 

 

4.6 Fertility, pregnancy and lactation 

 

Women of childbearing potential/ Contraception in males and females 

 

Women of childbearing age receiving docetaxel should be advised to avoid becoming pregnant, and to 

inform the treating physician immediately should this occur. An effective method of contraception 

should be used during treatment. 

 

Pregnancy 

 

There is no information on the use of docetaxel in pregnant women. Docetaxel has been shown to be 

both embryotoxic and foetotoxic in rabbits and rats, and to reduce fertility in rats (see section 5.3). As 

with other cytotoxic medicinal products, docetaxel may cause foetal harm when administered to 

pregnant women. Therefore, docetaxel must not be used during pregnancy unless clearly indicated.  

 

Breast-feeding 

 

Docetaxel is a lipophilic substance but it is not known whether it is excreted in human milk. 

Consequently, because of the potential for adverse reactions in nursing infants, breast feeding must be 

discontinued for the duration of docetaxel therapy. 

 

 

 

 



192 

Fertility 

 

In non clinical studies, docetaxel has genotoxic effects and may alter male fertility (see section 5.3). 

Therefore, men being treated with docetaxel are advised not to father a child during and up to 

6 months after treatment and to seek advice on conservation of sperm prior to treatment. 

 

 

4.7 Effects on ability to drive and use machines 

 

No studies on the effects on the ability to drive and use machines have been performed. The amount of 

alcohol in this medicinal product and the side effects of the product may impair the ability to drive or 

use machines (see sections 4.4 and 4.8). Therefore, patients should be warned of the potential impact 

of the amount of alcohol and the side effects of this medicinal product on the ability to drive or use 

machines, and be advised not to drive or use machines if they experience these side effects during 

treatment. 

 

 

4.8 Undesirable effects 

 

Summary of the safety profile for all indications 

 

The adverse reactions considered to be possibly or probably related to the administration of docetaxel 

have been obtained in: 

 

• 1,312 and 121 patients who received 100 mg/m² and 75 mg/m² of docetaxel as a single agent 
respectively. 

• 258 patients who received docetaxel in combination with doxorubicin. 

• 406 patients who received docetaxel in combination with cisplatin. 

• 92 patients treated with docetaxel in combination with trastuzumab. 

• 255 patients who received docetaxel in combination with capecitabine. 

• 332 patients (TAX327) who received docetaxel in combination with prednisone or prednisolone 
(clinically important treatment related adverse events are presented). 

• 1,276 patients (744 and 532 in TAX 316 and GEICAM 9805 respectively) who received 
docetaxel in combination with doxorubicin and cyclophosphamide (clinically important 

treatment related adverse events are presented). 

• 300 gastric adenocarcinoma patients (221 patients in the phase III part of the study and 
79 patients in the phase II part) who received docetaxel in combination with cisplatin and 

5-fluorouracil (clinically important treatment related adverse events are presented). 

• 174 and 251 head and neck cancer patients who received docetaxel in combination with 
cisplatin and 5-fluorouracil (clinically important treatment related adverse events are presented). 

• 545 patients (STAMPEDE study) who received docetaxel in combination with prednisone or 
prednisolone and ADT. 

 

These reactions were described using the NCI Common Toxicity Criteria (grade 3 = G3; 

grade 3-4 = G3/4; grade 4 = G4), the COSTART and the MedDRA terms. Frequencies are defined as: 
very common (≥ 1/10), common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare 

(≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from available 

data). 

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 

 

The most commonly reported adverse reactions of docetaxel alone are: neutropenia (which was 

reversible and not cumulative; the median day to nadir was 7 days and the median duration of severe 

neutropenia (< 500 cells/mm3) was 7 days), anaemia, alopecia, nausea, vomiting, stomatitis, diarrhoea 

and asthenia. The severity of adverse events of docetaxel may be increased when docetaxel is given in 

combination with other chemotherapeutic agents. 



193 

 

For combination with trastuzumab, adverse events (all grades) reported in ≥ 10% are displayed. There 

was an increased incidence of SAEs (40% vs. 31%) and Grade 4 AEs (34% vs. 23%) in the 

trastuzumab combination arm compared to docetaxel monotherapy. 

 

For combination with capecitabine, the most frequent treatment-related undesirable effects (≥ 5%) 

reported in a phase III study in breast cancer patients failing anthracycline treatment are presented (see 

capecitabine summary of product characteristics). 

 

For combination with ADT and with prednisone or prednisolone (STAMPEDE study), adverse events 

occurring occurring over the 6 cycles of treatment with docetaxel and having at least 2% higher 

incidence in the docetaxel treatment arm by comparison to the control arm, are presented, using the 

CTCAE grading scale. 

 

The following adverse reactions are frequently observed with docetaxel:  

 

Immune system disorders 

 

Hypersensitivity reactions have generally occurred within a few minutes following the start of the 

infusion of docetaxel and were usually mild to moderate. The most frequently reported symptoms 

were flushing, rash with or without pruritus, chest tightness, back pain, dyspnoea and fever or chills. 

Severe reactions were characterised by hypotension and/or bronchospasm or generalized 

rash/erythema (see section 4.4). 

 

Nervous system disorders 

 

The development of severe peripheral neurotoxicity requires a reduction of dose (see sections 4.2 and 

4.4). Mild to moderate neuro-sensory signs are characterised by paraesthesia, dysesthesia or pain 

including burning. Neuro-motor events are mainly characterised by weakness. 

 

Skin and subcutaneous tissue disorders 

 

Reversible cutaneous reactions have been observed and were generally considered as mild to 

moderate. Reactions were characterised by a rash including localised eruptions mainly on the feet and 

hands (including severe hand and foot syndrome), but also on the arms, face or thorax, and frequently 

associated with pruritus. Eruptions generally occurred within one week after the docetaxel infusion. 

Less frequently, severe symptoms such as eruptions followed by desquamation which rarely lead to 

interruption or discontinuation of docetaxel treatment were reported (see sections 4.2 and 4.4). Severe 

nail disorders are characterised by hypo- or hyperpigmentation and sometimes pain and onycholysis. 

 

General disorders and administration site conditions 

 

Infusion site reactions were generally mild and consisted of hyper pigmentation, inflammation, 

redness or dryness of the skin, phlebitis or extravasation and swelling of the vein.  

Fluid retention includes events such as peripheral oedema and less frequently pleural effusion, 

pericardial effusion, ascites and weight gain. The peripheral oedema usually starts at the lower 

extremities and may become generalised with a weight gain of 3 kg or more. Fluid retention is 

cumulative in incidence and severity (see section 4.4). 

 

Tabulated list of adverse reactions in breast cancer for DOCETAXEL KABI 100 mg/m² single agent 

 

MedDRA system 

organ classes 

Very common 

adverse reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infections 

(G3/4: 5.7%; including 

sepsis and pneumonia, 

Infection associated 

with G4 neutropenia 

(G3/4: 4.6%) 

  



194 

MedDRA system 

organ classes 

Very common 

adverse reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

fatal in 1.7%) 

Blood and lymphatic 

system disorders 

Neutropenia 

(G4: 76.4%); 

Anaemia 

(G3/4: 8.9%); 

Febrile neutropenia 

Thrombocytopenia 

(G4: 0.2%) 

  

Immune system 

disorders 

Hypersensitivity 

(G3/4: 5.3%) 

    

Metabolism and 

nutrition disorders 

Anorexia     

Nervous system 

disorders 

Peripheral sensory 

neuropathy 

(G3: 4.1%); 

Peripheral motor 

neuropathy 

(G3/4: 4%); 

Dysgeusia 

(severe: 0.07%) 

    

Cardiac disorders   Arrhythmia 

(G3/4: 0.7%) 

Cardiac failure 

Vascular disorders   Hypotension; 

Hypertension; 

Haemorrhage 

  

Respiratory, thoracic 

and mediastinal 

disorders 

Dyspnoea 

(severe: 2.7%) 

    

Gastrointestinal 

disorders 

Stomatitis 

(G3/4: 5.3%); 

Diarrhoea (G3/4: 4%); 

Nausea (G3/4: 4%); 

Vomiting (G3/4: 3%) 

Constipation 

(severe: 0.2%); 

Abdominal pain 

(severe: 1%); 

Gastrointestinal 

haemorrhage 

(severe: 0.3%) 

Oesophagitis 

(severe: 0.4%) 

Skin and subcutaneous 

tissue disorders 

Alopecia; 

Skin reaction 

(G3/4: 5.9%); 

Nail disorders 

(severe: 2.6%) 

    

Musculoskeletal and 

connective tissue 

disorders 

Myalgia 

(severe: 1.4%) 

Arthralgia   

General disorders and 

administration site 

conditions 

Fluid retention 

(severe: 6.5%); 

Asthenia 

(severe: 11.2%); 

Pain 

Infusion site reaction;  

Non-cardiac chest pain 

(severe: 0.4%) 

  

Investigations   G3/4 Blood bilirubin   



195 

MedDRA system 

organ classes 

Very common 

adverse reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

increased (< 5%); 

G3/4 Blood alkaline 

phosphatase increased 

(< 4%);G3/4 AST 

increased (< 3%); 

G3/4 ALT increased 

(< 2%) 

 

Description of selected adverse reactions in breast cancer for DOCETAXEL KABI 100 mg/m² single 

agent 

 

Blood and lymphatic system disorders 

Rare: bleeding episodes associated with grade 3/4 thrombocytopenia.  

 

Nervous system disorders 

Reversibility data are available among 35.3% of patients who developed neurotoxicity following 

docetaxel treatment at 100 mg/m² as single agent. The events were spontaneously reversible within 

3 months. 

 

Skin and subcutaneous tissue disorders 

Very rare: one case of alopecia non-reversible at the end of the study. 73% of the cutaneous reactions 

were reversible within 21 days. 

 

General disorders and administration site conditions 

The median cumulative dose to treatment discontinuation was more than 1,000 mg/m2 and the median 

time to fluid retention reversibility was 16.4 weeks (range 0 to 42 weeks). The onset of moderate and 

severe retention is delayed (median cumulative dose: 818.9 mg/m2) in patients with premedication 

compared with patients without premedication (median cumulative dose: 489.7 mg/m2); however, it 

has been reported in some patients during the early courses of therapy. 

 

Tabulated list of adverse reactions in  non-small cell lungcancer for DOCETAXEL KABI 75 mg/m² 

single agent 

 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Infections and infestations Infections (G3/4: 5%)   

Blood and lymphatic system 

disorders 

Neutropenia (G4: 54.2%); 

Anaemia (G3/4: 10.8%); 

Thrombocytopenia (G4: 1.7%) 

Febrile neutropenia 

Immune system disorders   Hypersensitivity (no severe) 

Metabolism and nutrition 

disorders 

Anorexia   

Nervous system disorders Peripheral sensory neuropathy 

(G3/4: 0.8%) 

Peripheral motor neuropathy 

(G3/4: 2.5%) 

Cardiac disorders   Arrhythmia (no severe) 

Vascular disorders   Hypotension 

Gastrointestinal disorders Nausea (G3/4: 3.3%); 

Stomatitis (G3/4: 1.7%); 

Vomiting (G3/4: 0.8%); 

Constipation 



196 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Diarrhoea (G3/4: 1.7%) 

Skin and subcutaneous tissue 

disorders 

Alopecia; 

Skin reaction (G3/4: 0.8%) 

Nail disorders (severe: 0.8%) 

Musculoskeletal and 

connective tissue disorders 

  Myalgia 

General disorders and 

administration site conditions 

Asthenia (severe: 12.4%); 

Fluid retention (severe: 0.8%); 

Pain 

  

Investigations   G3/4 Blood bilirubin 

increased (< 2%) 

 

Tabulated list of adverse reactions in breast cancer for DOCETAXEL KABI 75 mg/m² in combination 

with doxorubicin 

 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 7.8%)     

Blood and lymphatic 

system disorders 

Neutropenia 

(G4: 91.7%); 

Anaemia (G3/4: 9.4%); 

Febrile neutropenia; 

Thrombocytopenia 

(G4: 0.8%) 

    

Immune system 

disorders 

  Hypersensitivity 

(G3/4: 1.2%) 

  

Metabolism and 

nutrition disorders 

  Anorexia   

Nervous system 

disorders 

Peripheral sensory 

neuropathy (G3: 0.4%) 

Peripheral motor 

neuropathy 

(G3/4: 0.4%) 

  

Cardiac disorders   Cardiac failure; 

Arrhythmia (no 

severe) 

  

Vascular disorders     Hypotension 

Gastrointestinal 

disorders 

Nausea (G3/4: 5%); 

Stomatitis 

(G3/4: 7.8%); 

Diarrhoea 

(G3/4: 6.2%); 

Vomiting (G3/4: 5%); 

Constipation 

    

Skin and subcutaneous 

tissue disorders 

Alopecia; 

Nail disorders 

(severe: 0.4%); 

Skin reaction (no 

    



197 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

severe) 

Musculoskeletal and 

connective tissue 

disorders 

  Myalgia   

General disorders and 

administration site 

conditions 

Asthenia 

(severe: 8.1%); 

Fluid retention 

(severe: 1.2%); 

Pain 

Infusion site reaction   

Investigations   G3/4 Blood bilirubin 

increased (< 2.5%); 

G3/4 Blood alkaline 

phosphatase increased 

(< 2.5%) 

G3/4 AST increased 

(< 1%); 

G3/4 ALT increased 

(< 1%) 

 

Tabulated list of adverse reactions in non-small cell lung cancer for DOCETAXEL KABI 75 mg/m² in 

combination with cisplatin 

 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 5.7%)     

Blood and 

lymphatic system 

disorders 

Neutropenia (G4: 51.5%); 

Anaemia (G3/4: 6.9%); 

Thrombocytopenia 

(G4: 0.5%) 

Febrile neutropenia   

Immune system 

disorders 

Hypersensitivity 

(G3/4: 2.5%) 

    

Metabolism and 

nutrition disorders 

Anorexia     

Nervous system 

disorders 

Peripheral sensory 

neuropathy (G3: 3.7%); 

Peripheral motor 

neuropathy (G3/4: 2%) 

    

Cardiac disorders   Arrhythmia 

(G3/4: 0.7%) 

Cardiac failure 

Vascular disorders   Hypotension 

(G3/4: 0.7%) 

  

Gastrointestinal 

disorders 

Nausea (G3/4: 9.6%); 

Vomiting (G3/4: 7.6%); 

Diarrhoea (G3/4: 6.4%); 

Stomatitis (G3/4: 2%) 

Constipation   

Skin and 

subcutaneous 

tissue disorders 

Alopecia; 

Nail disorders 

(severe: 0.7%); 

Skin reaction (G3/4: 0.2%) 

    



198 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Musculoskeletal 

and connective 

tissue disorders 

Myalgia (severe: 0.5%)     

General disorders 

and administration 

site conditions 

Asthenia (severe: 9.9%); 

Fluid retention 

(severe: 0.7%); 

Fever (G3/4: 1.2%) 

Infusion site reaction; 

Pain 

  

Investigations   G3/4 Blood bilirubin 

increased (2.1%); G3/4 

ALT increased (1.3%) 

G3/4 AST increased 

(0.5%); G3/4 Blood 

alkaline phosphatase 

increased (0.3%) 

 

Tabulated list of adverse reactions in breast cancer for DOCETAXEL KABI 100 mg/m² in 

combination with trastuzumab 

 

MedDRA system 

organ classes 

Very common adverse reactions Common adverse reactions 

 

Blood and lymphatic 

system disorders 

Neutropenia (G3/4: 32%); 

Febrile neutropenia (includes 

neutropenia associated with fever and 

antibiotic use) or neutropenic sepsis  

  

Metabolism and 

nutrition disorders 

Anorexia   

Psychiatric disorders Insomnia   

Nervous system 

disorders 

Paraesthesia; Headache; Dysgeusia; 

Hypoaesthesia 

  

Eye disorders Lacrimation increased; Conjunctivitis   

Cardiac disorders   Cardiac failure 

Vascular disorders Lymphoedema   

Respiratory, thoracic 

and mediastinal 

disorders 

Epistaxis; Pharyngolaryngeal pain; 

Nasopharyngitis; Dyspnoea; 

Cough; Rhinorrhoea 

  

Gastrointestinal 

disorders 

Nausea; Diarrhoea; Vomiting; 

Constipation; Stomatitis; Dyspepsia; 

Abdominal pain 

  

Skin and 

subcutaneous tissue 

disorders 

Alopecia; Erythema; Rash; Nail 

disorders 

  

Musculoskeletal and 

connective tissue 

disorders 

Myalgia; Arthralgia; Pain in 

extremity; Bone pain; Back pain 

  

General disorders 

and administration 

site conditions 

Asthenia; Oedema peripheral; 

Pyrexia; Fatigue; Mucosal 

inflammation; Pain; Influenza like 

illness; Chest pain; Chills 

Lethargy 



199 

MedDRA system 

organ classes 

Very common adverse reactions Common adverse reactions 

 

Investigations Weight increased   

 

Description of selected adverse reactions in breast cancer for DOCETAXEL KABI 100 mg/m² in 

combination with trastuzumab 

 

Blood and lymphatic system disorders 

Very common: Haematological toxicity was increased in patients receiving trastuzumab and 

docetaxel, compared with docetaxel alone (32% grade 3/4 neutropenia versus 22%, using NCI-CTC 

criteria). Note that this is likely to be an underestimate since docetaxel alone at a dose of 100 mg/m2 is 

known to result in neutropenia in 97% of patients, 76% grade 4, based on nadir blood counts. The 

incidence of febrile neutropenia/neutropenic sepsis was also increased in patients treated with 

Herceptin plus docetaxel (23% versus 17% for patients treated with docetaxel alone). 

 

Cardiac disorders 

Symptomatic cardiac failure was reported in 2.2% of the patients who received docetaxel plus 

trastuzumab compared to 0% of patients given docetaxel alone. In the docetaxel plus trastuzumab arm, 

64% had received a prior anthracycline as adjuvant therapy compared with 55% in the docetaxel arm 

alone. 

 

Tabulated list of adverse reactions in breast cancer for DOCETAXEL KABI 75 mg/m² in combination 

with capecitabine 

 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Infections and infestations   Oral candidiasis (G3/4: < 1%) 

Blood and lymphatic system 

disorders 

Neutropenia (G3/4: 63%); 

Anaemia (G3/4: 10%) 

Thrombocytopenia (G3/4: 3%) 

Metabolism and nutrition 

disorders 

Anorexia (G3/4: 1%); 

Decreased appetite 

Dehydration (G3/4: 2%) 

Nervous system disorders Dysgeusia (G3/4: < 1%); 

Paraesthesia (G3/4: < 1%) 

 

Dizziness; 

Headache (G3/4: < 1%); 

Neuropathy peripheral 

Eye disorders Lacrimation increased   

Respiratory, thoracic and 

mediastinal disorders 

Pharyngolaryngeal pain 

(G3/4: 2%) 

Dyspnoea (G3/4: 1%); 

Cough (G3/4: < 1%); 

Epistaxis (G3/4: < 1%) 

Gastrointestinal disorders Stomatitis (G3/4: 18%); 

Diarrhoea (G3/4: 14%); 

Nausea (G3/4: 6%); 

Vomiting (G3/4: 4%); 

Constipation (G3/4: 1%); 

Abdominal pain (G3/4: 2%); 

Dyspepsia 

Abdominal pain upper; 

Dry mouth 

Skin and subcutaneous tissue 

disorders 

Hand-foot syndrome 

(G3/4: 24%); 

Alopecia (G3/4: 6%); 

Nail disorders (G3/4: 2%) 

Dermatitis; 

Rash erythematous 

(G3/4: < 1%); 

Nail discolouration; 

Onycholysis (G3/4: 1%) 



200 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Musculoskeletal and 

connective tissue disorders 

Myalgia (G3/4: 2%); 

Arthralgia (G3/4: 1%) 

Pain in extremity (G3/4: < 1%); 

Back pain (G3/4: 1%) 

General disorders and 

administration site conditions 

Asthenia (G3/4: 3%); 

Pyrexia (G3/4: 1%); 

Fatigue/weakness (G3/4: 5%); 

Oedema peripheral (G3/4: 1%) 

Lethargy; 

Pain 

Investigations   Weight decreased; 

G3/4 Blood bilirubin increased 

(9%) 

 

Tabulated list of adverse reactions in metastatic castration-resistant prostate cancer for DOCETAXEL 

KABI 75 mg/m² in combination with prednisone or prednisolone 

 

MedDRA system organ 

classes 

Very common adverse 

reactions 

Common adverse reactions 

Infections and infestations Infection (G3/4: 3.3%)   

Blood and lymphatic system 

disorders 

Neutropenia (G3/4: 32%); 

Anaemia (G3/4: 4.9%) 

Thrombocytopenia 

(G3/4: 0.6%); 

Febrile neutropenia 

Immune system disorders   Hypersensitivity (G3/4: 0.6%) 

Metabolism and nutrition 

disorders 

Anorexia (G3/4: 0.6%)   

Nervous system disorders Peripheral sensory neuropathy 

(G3/4: 1.2%); 

Dysgeusia (G3/4: 0%) 

Peripheral motor neuropathy 

(G3/4: 0%) 

Eye disorders   Lacrimation increased 

(G3/4: 0.6%) 

Cardiac disorders   Cardiac left ventricular 

function decrease (G3/4: 0.3%) 

Respiratory, thoracic and 

mediastinal disorders 

  Epistaxis (G3/4: 0%); 

Dyspnoea (G3/4: 0.6%); 

Cough (G3/4: 0%) 

Gastrointestinal disorders Nausea (G3/4: 2.4%); 

Diarrhoea (G3/4: 1.2%); 

Stomatitis/Pharyngitis 

(G3/4: 0.9%); 

Vomiting (G3/4: 1.2%) 

  

Skin and subcutaneous tissue 

disorders 

Alopecia; 

Nail disorders (no severe) 

Exfoliative rash (G3/4: 0.3%) 

Musculoskeletal and 

connective bone disorders 

  Arthralgia (G3/4: 0.3%); 

Myalgia (G3/4: 0.3%) 

General disorders and 

administration site conditions 

Fatigue (G3/4: 3.9%); 

Fluid retention (severe: 0.6%) 

  

 



201 

Tabulated list of adverse reactions in high-risk locally advanced or metastatic hormone-sensitive 

prostate cancer for DOCETAXEL KABI 75 mg/m² in combination with prednisone or prednisolone 

and ADT (STAMPEDE study)  

 

MedDRA system organ 

classes 

 

Very common adverse 

reactions 

Common adverse reactions 

Blood and lymphatic system 

disorders 

Neutropenia (G3-4: 12 %) 

Anaemia  

Febrile neutropenia (G3-4: 15%) 

 

Immune system disorders   Hypersensitivity (G3-4: 1%) 

Endocrine disorders  Diabetes (G3-4: 1%) 

Metabolism and nutrition 

disorders 

 Anorexia  

Psychiatric disorders Insomnia (G3: 1%)  

Nervous system disorders Peripheral sensory neuropathy 

(≥G3: 2%)a 

Headache 

 

Dizziness 

Eye disorders  Blurred vision 

Cardiac disorders  Hypotension (G3: 0%) 

 

Respiratory, thoracic and 

mediastinal disorders  

Dyspnea (G3: 1%) 

Coughing (G3: 0%) 

Upper respiratory tract infection 

(G3: 1%)  

Pharyngitis (G3: 0%) 

 

 

Gastrointestinal disorders  Diarrhea (G3: 3%) 

Stomatitis (G3: 0%) 

Constipation (G3: 0%) 

Nausea (G3: 1%) 

Dyspepsia 

Abdominal pain (G3: 0%) 

Flatulence 

Vomiting (G3: 1%) 

 

Skin and subcutaneous tissue 

disorders 

Alopecia (G3: 3%)a 

Nail changes (G3: 1%) 

Rash 

Musculoskeletal and 

connective tissue disorders 

Myalgia   

General disorders and 

administration site conditions 

Lethargy (G3-4: 2%) 

Flu-like symptoms (G3: 0%) 

Asthenia (G3: 0%) 

Fluid retention 

Fever (G3: 1%) 

Oral candidiasis  

Hypocalcaemia (G3: 0%) 

Hypophosphataemia (G3-4: 1%) 

Hypokalaemia (G3: 0%) 
a From the GETUG AFU15 study 
 

Tabulated list of adverse reactions in breast cancer for adjuvant therapy with DOCETAXEL KABI 

75 mg/m² in combination with doxorubicin and cyclophosphamide in patients with node-positive 

(TAX 316) and node-negative (GEICAM 9805) breast cancer - pooled data 

 



202 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 2.4%); 

Neutropenic infection 

(G3/4: 2.6%) 

    

Blood and 

lymphatic system 

disorders 

Anaemia (G3/4: 3%); 

Neutropenia 

(G3/4: 59.2%); 

Thrombocytopenia 

(G3/4: 1.6%); 

Febrile neutropenia 

(G3/4: NA) 

    

Immune system 

disorders 

  Hypersensitivity 

(G3/4: 0.6 %) 

  

Metabolism and 

nutrition disorders 

Anorexia (G3/4: 1.5%)     

Nervous system 

disorders 

Dysgeusia (G3/4: 0.6%); 

Peripheral sensory 

neuropathy 

(G3/4: < 0.1%) 

Peripheral motor 

neuropathy 

(G3/4: 0%) 

Syncope (G3/4: 0%); 

Neurotoxicity 

(G3/4: 0%); 

Somnolence (G3/4: 0%) 

Eye disorders  Conjunctivitis 

(G3/4: < 0.1%) 

Lacrimation 

increased 

(G3/4:  < 0.1%) 

  

Cardiac disorders   Arrhythmia 

(G3/4: 0.2%) 

  

Vascular disorders Hot flush (G3/4: 0.5%) Hypotension 

(G3/4: 0%); 

Phlebitis 

(G3/4: 0%) 

Lymphoedema 

(G3/4: 0%) 

Respiratory, 

thoracic and 

mediastinal 

disorders 

  Cough (G3/4: 0%)   

Gastrointestinal 

disorders 

Nausea (G3/4: 5.0%); 

Stomatitis (G3/4: 6.0%); 

Vomiting (G3/4: 4.2%); 

Diarrhoea (G3/4: 3.4%); 

Constipation 

(G3/4: 0.5%) 

Abdominal pain 

(G3/4: 0.4%) 

 

Skin and 

subcutaneous tissue 

disorders 

Alopecia 

(persisting: < 3%); 

Skin disorder  

(G3/4: 0.6%); 

Nail disorders 

(G3/4: 0.4%) 

    

Musculoskeletal 

and connective 

tissue disorders 

Myalgia (G3/4: 0.7%); 

Arthralgia (G3/4: 0.2%) 

    

Reproductive Amenorrhoea      



203 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

system and breast 

disorders 

(G3/4: NA) 

General disorders 

and administration 

site conditions 

Asthenia  

(G3/4: 10.0%); 

Pyrexia (G3/4: NA); 

Oedema peripheral 

(G3/4: 0.2%) 

    

Investigations   Weight increased 

(G3/4: 0%); 

Weight decreased 

(G3/4: 0.2%) 

  

 

Description of selected adverse reactions for adjuvant therapy with DOCETAXEL KABI 75 mg/m² in 

combination with doxorubicin and cyclophosphamide in patients with node-positive (TAX 

316) and node-negative (GEICAM 9805) breast cancer 

 

Nervous system disorders 

 In study TAX316 peripheral sensory neuropathy started during the treatment period and persisted into 

the follow-up period in 84 patients (11.3%) in TAC arm and 15 patients (2 %) in FAC arm. At the end 

of the follow-up period (median follow-up time of 8 years), peripheral sensory neuropathy was 

observed to be ongoing in 10 patients (1.3%) in TAC arm, and in 2 patients (0.3%) in FAC arm. 

In GEICAM 9805 study peripheral sensory neuropathy that started during the treatment period 

persisted into the follow-up period in 10 patients (1.9%) in TAC arm and 4 patients (0.8 %) in FAC 

arm. At the end of the follow-up period (median follow-up time of 10 years and 5 months), peripheral 

sensory neuropathy was observed to be ongoing in 3 patients (0.6%) in TAC arm, and in 1 patient 

(0.2%) in FAC arm. 

 

Cardiac disorders 

In study TAX316, 26 patients (3.5%) in the TAC arm and 17 patients (2.3%) in the FAC arm 

experienced congestive heart failure. All except one patient in each arm were diagnosed with CHF 

more than 30 days after the treatment period. Two patients in the TAC arm and 4 patients in the FAC 

arm died because of cardiac failure. 

In GEICAM 9805 study, 3 patients (0.6 %) in TAC arm and 3 patients (0.6 %) in FAC arm developed 

congestive heart failure during the follow-up period At the end of the follow-up period (actual median 

follow-up time of 10 years and 5 months), no patients  had CHF in TAC arm and 1 patient in TAC arm 

died because of dilated cardiomyopathy, and CHF was observed to be ongoing in 1 patient (0.2%) in 

FAC arm. 

 

Skin and subcutaneous tissue disorders 

In study TAX316 alopecia persisting into the follow-up period after the end of chemotherapy was 

reported in 687 of 744 TAC patients (92.3%) and 645 of 736 FAC patients (87.6%). 

At the end of the follow-up period (actual median follow-up time of8 years), alopecia was observed to 

be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2,2%). 

In GEICAM 9805 study alopecia that started during the treatment period and persisted into the follow-

up period was observed to be ongoing in 49 patients (9.2 %) in TAC arm and 35 patients (6.7 %) in 

FAC arm. Alopecia related to study drug started or worsened during the follow-up period in 

42 patients (7.9 %) in TAC arm and 30 patients (5.8 %) in FAC arm. At the end of the follow-up 

period (median follow-up time of 10 years and 5 months), alopecia was observed to be ongoing in 3 

patients (0.6%) in TAC arm, and in 1 patient (0.2%) in FAC arm.   

 

Reproductive system and breast disorders 

In TAX316 amenorrhoea that started during the treatment period and persisted into the follow-up 

period after the end of chemotherapy was reported in 202 of 744 TAC patients (27.2%) and 125 of 736 



204 

FAC patients (17.0%). Amenorrhea was observed to be ongoing at the end of the follow-up period 

(median follow-up time of 8 years) in 121 of 744 TAC patients (16.3%) and 86 FAC patients (11.7%). 

In GEICAM 9805 study amenorrhoea that started during the treatment period and persisted into the 

follow-up period was observed to be ongoing in 18 patients (3.4 %) in TAC arm and 5 patients (1.0 %) 

in FAC arm. At the end of the follow-up period (median follow-up time of 10 years and 5 months), 

amenorrhoea was observed to be ongoing in 7 patients (1.3%) in TAC arm, and in 4 patients (0.8%) in 

FAC arm. 

 

General disorders and administration site conditions 

 In study TAX316 peripheral oedema that started during the treatment period and persisted into the 

follow-up period after the end of chemotherapy was observed in 119 of 744 TAC patients (16.0%) and 

23 of 736 FAC patients (3.1%). At the end of the follow-up period (actual median follow-up time of 8 

years), peripheral oedema was ongoing in19 TAC patients (2.6%) and 4 FAC patients (0.5%).  

 

In study TAX316 lymphoedema that started during the treatment period and persisted into the follow-

up period after the end of chemotherapy was reported in 11 of 744 TAC patients (1.5%) and 1 of 736 

FAC patients (0.1%). At the end of the follow-up period (actual median follow-up time of 8 years), 

lymphoedema was observed to be ongoing in 6 TAC patients (0.8%) and 1 FAC patient (0.1%). 

In study TAX316 asthenia that started during the treatment period and persisted into the follow-up 

period after the end of chemotherapy was reported in 236 of 744 TAC patients (31.7%) and 180 of 736 

FAC patients (24.5%). At the end of the follow-up period (actual median follow-up time of 8 years), 

asthenia was observed to be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%). 

 

In study GEICAM 9805 peripheral oedema that started during the treatment period persisted into the 

follow-up period in 4 patients (0.8%) in TAC arm and in 2 patients (0.4%) in FAC arm. At the end of 

the follow-up period (median follow-up time of 10 years and 5 months), no patients (0%) in TAC arm 

had peripheral oedema and it was observed to be ongoing in 1 patient (0.2%) in FAC arm. 

Lymphoedema that started during the treatment period persisted into the follow-up period in 5 patients 

(0.9%) in TAC arm and 2 patients (0.4 %) in FAC arm. At the end of the follow-up period, 

lymphoedema was observed to be ongoing in 4 patients (0.8%) in TAC arm, and in 1 patient (0.2%) in 

FAC arm.  

 

Asthenia that started during the treatment period and persisted into the follow-up period was observed 

to be ongoing in 12 patients (2.3 %) in TAC arm and 4 patients (0.8 %) in FAC arm. At the end of the 

follow-up period, asthenia was observed to be ongoing in 2 patients (0.4%) in TAC arm, and in 2 

patients (0.4%) in FAC arm. 

 

Acute leukaemia / Myelodysplastic syndrome 

After 10 years of follow up in study TAX316, acute leukaemia was reported in 3 of 744 TAC patients 

(0.4%) and in 1 of 736 FAC patients (0.1%). One TAC patient (0.1%) and 1 FAC patient (0.1%) died 

due to AML during the follow-up period (median follow-up time of 8 years). Myelodysplastic 

syndrome was reported in 2 of 744 TAC patients (0.3%) and in 1 of 736 FAC patients (0.1%).  

After 10 years of follow-up in GEICAM 9805 study, acute leukaemia occurred in 1 of 532 (0.2%) 

patients in TAC arm. No cases were reported in patients in FAC arm. No patient was diagnosed with 

myelodysplastic syndrome in either treatment groups. 

 

Neutropenic complications 

Table below shows that the incidence of Grade 4 neutropenia, febrile neutropenia and neutropenic 

infection was decreased in patients who received primary G-CSF prophylaxis after it was made 

mandatory in the TAC arm – GEICAM study. 

 

Neutropenic complications in patients receiving TAC with or without primary G-CSF prophylaxis 

(GEICAM 9805) 

 

 

 

 



205 

 Without primary 

G-CSF prophylaxis 

(n = 111) 

n (%) 

With primary 

G-CSF prophylaxis 

(n = 421) 

n (%) 

Neutropenia (Grade 4) 104 (93.7) 135 (32.1) 

Febrile neutropenia 28 (25.2) 23 (5.5) 

Neutropenic infection 14 (12.6) 21 (5.0) 

Neutropenic infection 

(Grade 3-4) 

2 (1.8) 5 (1.2) 

 

Tabulated list of adverse reactions in gastric adenocarcinoma center for DOCETAXEL KABI 

75 mg/m² in combination with cisplatin and 5-fluorouracil 

 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse reactions 

Infections and 

infestations 

Neutropenic infection; 

Infection (G3/4: 11.7%) 

  

Blood and lymphatic 

system disorders 

Anaemia (G3/4: 20.9%); 

Neutropenia (G3/4: 83.2%); 

Thrombocytopenia (G3/4: 8.8%); 

Febrile neutropenia  

  

Immune system 

disorders 

Hypersensitivity (G3/4: 1.7%)   

Metabolism and 

nutrition disorders 

Anorexia (G3/4: 11.7%)   

Nervous system 

disorders 

Peripheral sensory neuropathy 

(G3/4: 8.7%) 

Dizziness (G3/4: 2.3%); 

Peripheral motor neuropathy 

(G3/4: 1.3%) 

Eye disorders   Lacrimation increased (G3/4: 0%) 

Ear and labyrinth 

disorders 

  Hearing impaired (G3/4: 0%) 

Cardiac disorders   Arrhythmia (G3/4: 1.0%) 

Gastrointestinal 

disorders 

Diarrhoea (G3/4: 19.7%); 

Nausea (G3/4: 16%); 

Stomatitis (G3/4: 23.7%); 

Vomiting (G3/4: 14.3%) 

Constipation (G3/4: 1.0%); 

Gastrointestinal pain (G3/4: 1.0%); 

Oesophagitis/dysphagia/ 

odynophagia (G3/4: 0.7%) 

Skin and subcutaneous 

tissue disorders 

Alopecia (G3/4: 4.0%) Rash pruritus (G3/4: 0.7%); 

Nail disorders (G3/4: 0.7%); 

Skin exfoliation (G3/4: 0%) 

General disorders and 

administration site 

conditions 

Lethargy (G3/4: 19.0%); 

Fever (G3/4: 2.3%); 

Fluid retention (severe/life-

threatening: 1%) 

  

 

Description of selected adverse reactions in gastric adenocarcinoma cancer for DOCETAXEL KABI 

75 mg/m2 in combination with cisplatin and 5-fluorouracil 

 

Blood and lymphatic system disorders 

Febrile neutropenia and neutropenic infection occurred in 17.2% and 13.5% of patients respectively, 

regardless of G-CSF use. G-CSF was used for secondary prophylaxis in 19.3% of patients (10.7% of 



206 

the cycles). Febrile neutropenia and neutropenic infection occurred respectively in 12.1% and 3.4% of 

patients when patients received prophylactic G-CSF, in 15.6% and 12.9% of patients without 

prophylactic G-CSF (see section 4.2). 

 

Tabulated list of adverse reactions in head and neck cancer for DOCETAXEL KABI 75 mg/m² in 

combination with cisplatin and 5-fluorouracil  

 

• Induction chemotherapy followed by radiotherapy (TAX 323)  
 

MedDRA system 

organ classes 

Very common adverse 

reactions 

 

Common adverse 

reactions 

 

Uncommon 

adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 6.3%); 

Neutropenic infection 

    

Neoplasms benign, 

malignant and 

unspecified (incl 

cysts and polyps) 

  Cancer pain (G3/4: 0.6%)   

Blood and lymphatic 

system disorders 

Neutropenia 

(G3/4: 76.3%); 

Anaemia (G3/4: 9.2%); 

Thrombocytopenia 

(G3/4: 5.2%) 

Febrile neutropenia   

Immune system 

disorders 

  Hypersensitivity (no 

severe) 

  

Metabolism and 

nutrition disorders 

Anorexia (G3/4: 0.6%)     

Nervous system 

disorders 

Dysgeusia/Parosmia; 

Peripheral sensory 

neuropathy (G3/4: 0.6%) 

Dizziness   

Eye disorders   Lacrimation increased; 

Conjunctivitis  

  

Ear and labyrinth 

disorders 

  Hearing impaired   

Cardiac disorders   Myocardial ischemia 

(G3/4: 1.7%) 

Arrhythmia 

(G3/4: 0.6%) 

Vascular disorders   Venous disorder 

(G3/4: 0.6%) 

  

Gastrointestinal 

disorders 

Nausea (G3/4: 0.6%); 

Stomatitis (G3/4: 4.0%); 

Diarrhoea (G3/4: 2.9%); 

Vomiting (G3/4: 0.6%) 

Constipation; 

Esophagitis/dysphagia/ 

odynophagia 

(G3/4: 0.6%); 

Abdominal pain; 

Dyspepsia; 

Gastrointestinal 

haemorrhage 

(G3/4: 0.6%)  

  

Skin and 

subcutaneous tissue 

disorders 

Alopecia (G3/4: 10.9%) Rash pruritic; 

Dry skin; 

Skin exfoliative 

  



207 

MedDRA system 

organ classes 

Very common adverse 

reactions 

 

Common adverse 

reactions 

 

Uncommon 

adverse 

reactions 

(G3/4: 0.6%) 

Musculoskeletal and 

connective tissue 

disorders 

  Myalgia (G3/4: 0.6%)   

General disorders and 

administration site 

conditions 

Lethargy (G3/4: 3.4%); 

Pyrexia (G3/4: 0.6%); 

Fluid retention; 

Oedema 

    

Investigations   Weight increased   

 

• Induction chemotherapy followed by chemoradiotherapy (TAX 324)  
 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Infections and 

infestations 

Infection (G3/4: 3.6%) 

  

Neutropenic 

infection 

  

Neoplasms benign, 

malignant and 

unspecified (incl 

cysts and polyps) 

  Cancer pain 

(G3/4: 1.2%) 

  

Blood and lymphatic 

system disorders 

Neutropenia 

(G3/4: 83.5%); 

Anaemia (G3/4: 12.4%); 

Thrombocytopenia 

(G3/4: 4.0%); 

Febrile neutropenia 

    

Immune system 

disorders 

    Hypersensitivity 

Metabolism and 

nutrition disorders 

Anorexia (G3/4: 12.0%)     

Nervous system 

disorders 

Dysgeusia/Parosmia 

(G3/4: 0.4%); 

Peripheral sensory 

neuropathy (G3/4: 1.2%) 

Dizziness 

(G3/4: 2.0%); 

Peripheral motor 

neuropathy 

(G3/4: 0.4%) 

  

Eye disorders   Lacrimation 

increased 

Conjunctivitis 

Ear and labyrinth 

disorders 

Hearing impaired 

(G3/4: 1.2%) 

    

Cardiac disorders   Arrhythmia 

(G3/4: 2.0%) 

Ischemia myocardial 

Vascular disorders     Venous disorder 

Gastrointestinal 

disorders 

Nausea (G3/4: 13.9%); 

Stomatitis (G3/4: 20.7%); 

Vomiting (G3/4: 8.4%); 

Dyspepsia 

(G3/4: 0.8%); 

Gastrointestinal pain 

  



208 

MedDRA system 

organ classes 

Very common adverse 

reactions 

Common adverse 

reactions 

Uncommon adverse 

reactions 

Diarrhoea (G3/4: 6.8%); 

Esophagitis/dysphagia/ 

odynophagia 

(G3/4: 12.0%); 

Constipation (G3/4: 0.4%) 

(G3/4: 1.2%); 

Gastrointestinal 

haemorrhage 

(G3/4: 0.4%) 

Skin and 

subcutaneous tissue 

disorders 

Alopecia (G3/4: 4.0%); 

Rash pruritic 

Dry skin ; 

Desquamation 

  

Musculoskeletal, 

connective tissue 

bone disorders 

  Myalgia 

(G3/4: 0.4%) 

  

General disorders and 

administration site 

conditions 

Lethargy (G3/4: 4.0%); 

Pyrexia (G3/4: 3.6%); 

Fluid retention (G3/4: 1.2); 

Oedema (G3/4: 1.2%) 

    

Investigations Weight decreased   Weight increased 

 

Post-marketing experience 

 

Neoplasms benign, malignant and unspecified (incl cysts and polyps) 

 Second primary malignancies (frequency not known), including non-Hodgkin lymphoma have been 

reported in association with docetaxel when used in combination with other anticancer treatments 

known to be associated with second primary malignancies. Acute myeloid leukemia and 

myelodysplastic syndrome have been reported (frequency uncommon) in pivotal clinical studies in 

breast cancer with TAC regimen. 

 

Blood and lymphatic system disorders 

Bone marrow suppression and other haematologic adverse reactions have been reported. Disseminated 

intravascular coagulation (DIC), often in association with sepsis or multi-organ failure, has been 

reported. 

 

Immune system disorders 

Some cases of anaphylactic shock, sometimes fatal, have been reported. 

Hypersensitivity reactions (frequency not known) have been reported with docetaxel in patients who 

previously experienced hypersensitivity reactions to paclitaxel. 

 

Nervous system disorders 

Rare cases of convulsion or transient loss of consciousness have been observed with docetaxel 

administration. These reactions sometimes appear during the infusion of the medicinal product. 

 

Eye disorders 

Very rare cases of transient visual disturbances (flashes, flashing lights, scotomata) typically occurring 

during infusion of the medicinal product and in association with hypersensitivity reactions have been 

reported. These were reversible upon discontinuation of the infusion. Cases of lacrimation with or 

without conjunctivitis, as cases of lacrimal duct obstruction resulting in excessive tearing have been 

rarely reported. Cases of cystoid macular oedema (CMO) have been reported in patients treated with 

docetaxel. 

 

Ear and labyrinth disorders 

Rare cases of ototoxicity, hearing impaired and/or hearing loss have been reported. 

 

 



209 

Cardiac disorders 

Rare cases of myocardial infarction have been reported. 

Ventricular arrhythmia including ventricular tachycardia (frequency not known), sometimes fatal, has 

been reported in patients treated with docetaxel in combination regimens including doxorubicin, 5-

fluorouracil and/ or cyclophosphamide. 

 

Vascular disorders 

Venous thromboembolic events have rarely been reported. 

 

Respiratory, thoracic and mediastinal disorders 

Acute respiratory distress syndrome and cases of interstitial pneumonia/ pneumonitis, interstitial lung 
disease, pulmonary fibrosis and respiratory failure sometimes fatal have rarely been reported. Rare 

cases of radiation pneumonitis have been reported in patients receiving concomitant radiotherapy. 

 

Gastrointestinal disorders 

Rare cases of enterocolitis, including colitis, ischemic colitis, and neutropenic enterocolitis, have been 

reported with a potential fatal outcome (frequency not known). 

Rare occurrences of dehydration have been reported as a consequence of gastrointestinal events 

including enterocolitis and gastrointestinal perforation.  

Rare cases of ileus and intestinal obstruction have been reported. 

 

Hepatobiliary disorders 

Very rare cases of hepatitis, sometimes fatal primarily in patients with pre-existing liver disorders, 

have been reported. 

 

Skin and subcutaneous tissue disorders 

Cases of cutaneous lupus erythematosus, bullous eruptions such as erythema multiforme and severe 

cutaneous adverse reactions such as Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis 

(TEN) and Acute Generalized Exanthematous Pustulosis (AGEP) have been reported with docetaxel. 

Scleroderma-like changes usually preceded by peripheral lymphoedema have been reported with 

docetaxel. Cases of permanent alopecia (frequency not known) have been reported. 

 

Renal and urinary disorders 

Renal insufficiency and renal failure have been reported. In about 20% of these cases there were no 

risk factors for acute renal failure such as concomitant nephrotoxic medicinal products and 

gastrointestinal disorders. 

 

General disorders and administration site conditions 

Radiation recall phenomena have rarely been reported. 

Injection site recall reaction (recurrence of skin reaction at a site of previous extravasation following 

administration of docetaxel at a different site) has been observed at the site of previous extravasation 

(frequency not known). 

Fluid retention has not been accompanied by acute episodes of oliguria or hypotension. Dehydration 

and pulmonary oedema have rarely been reported. 

 

Metabolism and nutrition disorders 

Cases of electrolyte imbalance have been reported. Cases of hyponatraemia have been reported, 

mostly associated with dehydration, vomiting and pneumonia. Hypokalaemia, hypomagnesaemia, and 

hypocalcaemia were observed, usually in association with gastrointestinal disorders and in particular 

with diarrhoea. 

 

Reporting of suspected adverse reactions 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 



210 

 

 

4.9 Overdose 

 

There were a few reports of overdose. There is no known antidote for docetaxel overdose. In case of 

overdose, the patient should be kept in a specialised unit and vital functions closely monitored. In 

cases of overdose, exacerbation of adverse events may be expected. The primary anticipated 

complications of overdose would consist of bone marrow suppression, peripheral neurotoxicity and 

mucositis. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. 

Other appropriate symptomatic measures should be taken, as needed. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: antineoplastic agents, plant alkaloids and other natural products, taxanes, 

ATC Code: L01CD02  

 

Mechanism of action 

 

Docetaxel is an antineoplastic agent which acts by promoting the assembly of tubulin into stable 

microtubules and inhibits their disassembly which leads to a marked decrease of free tubulin. The 

binding of docetaxel to microtubules does not alter the number of protofilaments. 

 

Docetaxel has been shown in vitro to disrupt the microtubular network in cells which is essential for 

vital mitotic and interphase cellular functions. 

 

Pharmacodynamic effects 

 

Docetaxel was found to be cytotoxic in vitro against various murine and human tumour cell lines and 

against freshly excised human tumour cells in clonogenic assays. Docetaxel achieves high intracellular 

concentrations with a long cell residence time. In addition, docetaxel was found to be active on some 

but not all cell lines over expressing the p-glycoprotein which is encoded by the multidrug resistance 

gene. In vivo, docetaxel is schedule independent and has a broad spectrum of experimental anti-tumour 

activity against advanced murine and human grafted tumours. 

 

Clinical efficacy and safety 

 

Breast cancer 

 

DOCETAXEL KABI in combination with doxorubicin and cyclophosphamide: adjuvant therapy 

 

Patients with operable node-positive breast cancer (TAX 316) 

 

Data from a multi-centre open-label randomised study support the use of docetaxel for the adjuvant 

treatment of patients with operable node-positive breast cancer and KPS ≥ 80%, between 18 and 

70 years of age. After stratification according to the number of positive lymph nodes (1-3, 

4+), 1491 patients were randomised to receive either docetaxel 75 mg/m2 administered 1-hour after 

doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (TAC arm), or doxorubicin 50 mg/m2 

followed by fluorouracil 500 mg/m2 and cyclosphosphamide 500 mg/m2 (FAC arm). Both regimens 

were administered once every 3 weeks for 6 cycles. Docetaxel was administered as a 1-hour infusion, 

all other medicinal products were given as intravenous bolus on day one. G-CSF was administered as 

secondary prophylaxis to patients who experienced complicated neutropenia (febrile neutropenia, 

prolonged neutropenia, or infection). Patients on the TAC arm received antibiotic prophylaxis with 

ciprofloxacin 500 mg orally twice daily for 10 days starting on day 5 of each cycle, or equivalent. In 

both arms, after the last cycle of chemotherapy, patients with positive oestrogen and/or progesterone 



211 

receptors received tamoxifen 20 mg daily for up to 5 years. Adjuvant radiation therapy was prescribed 

according to guidelines in place at participating institutions and was given to 69% of patients who 

received TAC and 72% of patients who received FAC. Two interim analyses and one final analysis 

were performed. The first interim analysis was planned 3 years after the date when half of study 

enrolment was done. The second interim analysis was done after 400 DFS events had been recorded 

overall, which led to a median follow-up of 55 months. The final analysis was performed when all 

patients had reached their 10-year follow-up visit (unless they had a DFS event or were lost to follow 

up before). Disease-free survival (DFS) was the primary efficacy endpoint and Overall survival (OS) 

was the secondary efficacy endpoint. 

 

A final analysis was performed with an actual median follow up of 96 months. Significantly longer 

disease-free survival for the TAC arm compared to the FAC arm was demonstrated. Incidence of 

relapses at 10 years was reduced in patients receiving TAC compared to those who received FAC 

(39% versus 45%, respectively) i.e. an absolute risk reduction by 6% (p = 0.0043). Overall survival at 

10 years was also significantly increased with TAC compared to FAC (76% versus 69%, respectively) 

i.e. an absolute reduction of the risk of death by 7% (p = 0.002). As the benefit observed in patients 

with 4+ nodes was not statistically significant on DFS and OS, the positive benefit/risk ratio for TAC 

in patients with 4+ nodes was not fully demonstrated at the final analysis. 

 

Overall, the study results demonstrate a positive benefit risk ratio for TAC compared to FAC. 

 

TAC-treated patient subsets according to prospectively defined major prognostic factors were 

analysed:  

 

  Disease free survival Overall Survival 

Patient 

subset 

Number 

of patients 

Hazard 

ratio* 

95% CI p = Hazard 

ratio* 

95% CI p = 

No of 

positive 

nodes 

Overall 

1-3 

4+ 

 

 

 

745 

467 

278 

 

 

 

0.80 

0.72 

0.87 

 

 

 

0.68-0.93 

0.58-0.91 

0.70-1.09 

 

 

 

0.0043 

0.0047 

0.2290 

 

 

 

0.74 

0.62 

0.87 

 

 

 

0.61-0.90 

0.46-0.82 

0.67-1.12 

 

 

 

0.0020 

0.0008 

0.2746 

*a hazard ratio of less than 1 indicates that TAC is associated with a longer disease-free survival and 

overall survival compared to FAC  

 

Patients with operable node-negative breast cancer eligible to receive chemotherapy (GEICAM 9805) 

 

Data from a multi-centre open-label randomised trial support the use of DOCETAXEL KABI for the 

adjuvant treatment of patients with operable node-negative breast cancer eligible to receive 

chemotherapy. 1060 patients were randomised to receive either DOCETAXEL KABI 75 mg/m2 

administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (539 patients in 

TAC arm), or doxorubicin 50 mg/m2 followed by fluorouracil 500 mg/m2 and cyclosphosphamide 

500 mg/m2 (521 patients in FAC arm), as adjuvant treatment of operable node-negative breast cancer 

patients with high risk of relapse according to 1998 St. Gallen criteria (tumour size > 2 cm and/or 

negative ER and PR and/or high histological/nuclear grade (grade 2 to 3) and /or age < 35 years).). 

Both regimens were administered once every 3 weeks for 6 cycles. DOCETAXEL KABI was 

administered as a 1-hour infusion, all other medicinal product were given intraveinously on day 1 

every three weeks. Primary prophylactic G-CSF was made mandatory in TAC arm after 230 patients 

were randomised. The incidence of Grade 4 neutropenia, febrile neutropenia and neutropenic infection 

was decreased in patients who received primary G-CSF prophylaxis (see section 4.8). In both arms, 

after the last cycle of chemotherapy, patients with ER+ and/or PgR+ tumours received tamoxifen 

20 mg once a day for up to 5 years. Adjuvant radiation therapy was administered according to 

guidelines in place at participating institutions and was given to 57.3% of patients who received TAC 

and 51.2% of patients who received FAC. 



212 

 

One primary analysis and one updated analysis were performed. The primary analysis was 

done when all patients had a follow-up of greater than 5 years (median follow-up time of 77 

months). The updated analysis was performed when all patients had reached their 10-year 

(median follow up time of 10 years and 5 months) follow-up visit (unless they had a DFS 

event or were lost to follow-up previously). Disease-free survival (DFS) was the primary 

efficacy endpoint and Overall survival (OS) was the secondary efficacy endpoint. 
At the median follow-up was time of 77 months, significantly longer disease-free survival for the TAC 

arm compared to the FAC arm was demonstrated. TAC-treated patients had a 32% reduction in the 

risk of relapse compared to those treated with FAC (hazard ratio = 0.68, 95% CI (0.49-0.93), 

p = 0.01). At the median follow up time of 10 years and 5 months, TAC-treated patients had a 16,5% 

reduction in the risk of relapse compared to those treated with FAC (hazard ratio = 0.84, 95% CI 

(0.65-1.08), p=0.1646). DFS data were not statistically significant but were still associated with a 

positive trend in favour of TAC.   

 

At the median follow-up time of 77 months overall survival (OS) was also longer in the TAC arm with 

TAC-treated patients having a 24% reduction in the risk of death compared to FAC (hazard ratio = 

0.76, 95% CI (0.46-1.26, p = 0.29). However, the distribution of OS was not significantly different 

between the 2 groups. 

At the median follow up time of 10 years and 5 months, TAC-treated patients had a 9% reduction in 

the risk of death compared to FAC-treated patients (hazard ratio = 0.91, 95% CI (0.63-1.32)).  

The survival rate was 93.7% in the TAC arm and 91.4 % in the FAC arm, at the 8-year follow-up time 

point, and 91.3 % in the TAC arm and 89 % in the FAC arm, at the 10-year follow-up time point. 

 

The positive benefit risk ratio for TAC compared to FAC remained unchanged.   

 

TAC-treated patient subsets according to prospectively defined major prognostic factors were analysed 

in the primary analysis (at the median follow-up time of 77 months) (see table below): 
 

Subset Analyses-Adjuvant Therapy in Patients with Node-negative Breast Cancer Study 

(Intent-to-Treat Analysis) 

 

Patient subset Number of patients 

in TAC group 

Disease Free Survival 

Hazard ratio* 95% CI 

Overall 539 0.68 0.49-0.93 

Age category 1 

<50 years  

≥50 years 

 

260 

279  

 

0.67 

0.67  

 

0.43-1.05 

0.43-1.05 

Age category 2 

<35 years 

≥35 years 

 

42 

497 

 

0.31 

0.73 

 

0.11-0.89 

0.52-1.01 

Hormonal receptor 

status 

Negative  

Positive 

 

 

195 

344 

 

 

0.7 

0.62 

 

 

0.45-1.1 

0.4-0.97 

Tumour size 

≤2 cm  

>2 cm 

 

285 

254 

 

0.69 

0.68 

 

0.43-1.1 

0.45-1.04 

Histological grade 

Grade1 (includes grade 

not assessed) 

Grade 2  

Grade 3 

 

64 

 

216 

259 

 

0.79 

 

0.77 

0.59 

 

0.24-2.6 

 

0.46-1.3 

0.39-0.9 

Menopausal status 

Pre-Menopausal  

Post-Menopausal  

 

285 

254 

 

0.64 

0.72 

 

0.40-1 

0.47-1.12 



213 

*a hazard ratio (TAC/FAC) of less than 1 indicates that TAC is associated with a longer disease free 

survival compared to FAC. 

 

Exploratory subgroup analyses for disease-free survival for patients who meet the 2009 St. Gallen 

chemotherapy criteria – (ITT population) were performed and presented here below 

 
 TAC 

 

FAC 

 

Hazard ratio 

(TAC/FAC) 

 

 

Subgroups (n=539) (n=521) (95% CI) p-value 

Meeting relative 

 indication 

for chemotherapya 

    

No 18/214 

(8.4%) 

26/227 

(11.5%) 

0.796 

(0.434 - 1.459) 

0.4593 

Yes 48/325 

(14.8%) 

69/294 

(23.5%) 

0.606 

(0.42 - 0.877) 

0.0072 

TAC = docetaxel, doxorubicin and cyclophosphamide 

FAC = 5-fluorouracil, doxorubicin and cyclophosphamide 

CI = confidence interval 

ER = oestrogen receptor 

PR = progesterone receptor 
a ER/PR-negative or Grade 3 or tumour size > 5 cm 

 

The estimated hazard ratio was using Cox proportional hazard model with treatment group as the 

factor. 

 

DOCETAXEL KABI as single agent 

 

Two randomised phase III comparative studies, involving a total of 326 alkylating or 

392 anthracycline failure metastatic breast cancer patients, have been performed with docetaxel at the 

recommended dose and regimen of 100 mg/m² every 3 weeks. 

 

In alkylating-failure patients, docetaxel was compared to doxorubicin (75 mg/m² every 3 weeks). 

Without affecting overall survival time (docetaxel 15 months vs. doxorubicin 14 months, p = 0.38) or 

time to progression (docetaxel 27 weeks vs. doxorubicin 23 weeks, p = 0.54), docetaxel increased 

response rate (52% vs. 37%, p = 0.01) and shortened time to response (12 weeks vs. 23 weeks, 

p= 0.007). Three docetaxel patients (2%) discontinued the treatment due to fluid retention, whereas 

15 doxorubicin patients (9%) discontinued due to cardiac toxicity (three cases of fatal congestive heart 

failure). 

 

In anthracycline-failure patients, docetaxel was compared to the combination of mitomycin C and 

vinblastine (12 mg/m² every 6 weeks and 6 mg/m² every 3 weeks). Docetaxel increased response rate 

(33% vs. 12%, p < 0.0001), prolonged time to progression (19 weeks vs. 11 weeks, p= 0.0004) and 

prolonged overall survival (11 months vs. 9 months, p= 0.01). 

 

During these two phase III studies, the safety profile of docetaxel was consistent with the safety profile 

observed in phase II studies (see section 4.8). 

 

An open-label, multi-centre, randomised phase III study was conducted to compare docetaxel 

monotherapy and paclitaxel in the treatment of advanced breast cancer in patients whose previous 

therapy should have included an anthracycline. A total of 449 patients were randomised to receive 

either docetaxel monotherapy 100 mg/m² as a 1 hour infusion or paclitaxel 175 mg/m² as a 3 hour 

infusion. Both regimens were administered every 3 weeks. 

Without affecting the primary endpoint, overall response rate (32% vs 25%, p = 0.10), docetaxel 

prolonged median time to progression (24.6 weeks vs 15.6 weeks; p < 0.01) and median survival 

(15.3 months vs 12.7 months; p = 0.03). 



214 

More grade 3/4 adverse events were observed for docetaxel monotherapy (55.4%) compared to 

paclitaxel (23.0%). 

 

DOCETAXEL KABI in combination with doxorubicin 

 

One large randomised phase III study, involving 429 previously untreated patients with metastatic 
disease, has been performed with doxorubicin (50 mg/m²) in combination with docetaxel (75 mg/m²) 

(AT arm) versus doxorubicin (60 mg/m²) in combination with cyclophosphamide (600 mg/m²) (AC 

arm). Both regimens were administered on day 1 every 3 weeks.  

• Time to progression (TTP) was significantly longer in the AT arm versus AC arm, p = 0.0138. 
The median TTP was 37.3 weeks (95% CI: 33.4 - 42.1) in AT arm and 31.9 weeks (95% CI: 27.4 - 

36.0) in AC arm.  

• Overall response rate (ORR) was significantly higher in the AT arm versus AC arm, p = 0.009. 
The ORR was 59.3% (95% CI: 52.8 - 65.9) in AT arm versus 46.5% (95% CI: 39.8 - 53.2) in AC 

arm.  

 

In this study, AT arm showed a higher incidence of severe neutropenia (90% versus 68.6%), febrile 

neutropenia (33.3% versus 10%), infection (8% versus 2.4%), diarrhoea (7.5% versus 1.4%), asthenia 

(8.5% versus 2.4%), and pain (2.8% versus 0%) than AC arm. On the other hand, AC arm showed a 

higher incidence of severe anaemia (15.8% versus 8.5%) than AT arm, and, in addition, a higher 

incidence of severe cardiac toxicity: congestive heart failure (3.8% versus 2.8%), absolute LVEF 

decrease ≥ 20% (13.1% versus 6.1%), absolute LVEF decrease ≥ 30% (6.2% versus 1.1%). Toxic 

deaths occurred in 1 patient in the AT arm (congestive heart failure) and in 4 patients in the AC arm 

(1 due to septic shock and 3 due to congestive heart failure).  

In both arms, quality of life measured by the EORTC questionnaire was comparable and stable during 

treatment and follow-up.  

 

DOCETAXEL KABI in combination with trastuzumab 

 

Docetaxel in combination with trastuzumab was studied for the treatment of patients with metastatic 

breast cancer whose tumours overexpress HER2, and who previously had not received chemotherapy 

for metastatic disease. One hundred eighty six patients were randomised to receive docetaxel 
(100 mg/m2) with or without trastuzumab; 60% of patients received prior anthracycline-based adjuvant 

chemotherapy. Docetaxel plus trastuzumab was efficacious in patients whether or not they had 

received prior adjuvant anthracyclines. The main test method used to determine HER2 positivity in 

this pivotal study was immunohistochemistry (IHC). A minority of patients were tested using 

fluorescence in-situ hybridization (FISH). In this study, 87% of patients had disease that was IHC 3+, 

and 95% of patients entered had disease that was IHC 3+ and/or FISH positive. Efficacy results are 

summarized in the following table:  

 

Parameter Docetaxel plus trastuzumab1 

n = 92 

Docetaxel1 

n = 94 

Response rate 

(95% CI) 

61% 

(50-71) 

34% 

(25-45) 

Median duration of response 

(months) 

(95% CI)  

11.4 

(9.2-15.0) 

5.1 

(4.4-6.2) 

Median TTP (months) 

(95% CI) 

10.6 

(7.6-12.9) 

5.7 

(5.0-6.5) 

Median survival (months) 

(95% CI) 

30.52 

(26.8-ne) 

22.12 

(17.6-28.9) 

TTP = time to progression; “ne” indicates that it could not be estimated or it was not yet reached.  
1Full analysis set (intent-to-treat)  
2 Estimated median survival  



215 

 

DOCETAXEL KABI in combination with capecitabine 

 

Data from onemulti-centre, randomised, controlled phase III clinical study support the use of 
docetaxel in combination with capecitabine for treatment of patients with locally advanced or 

metastatic breast cancer after failure of cytotoxic chemotherapy, including an anthracycline. In this 

study, 255 patients were randomised to treatment with docetaxel (75 mg/m2 as a 1 hour intravenous 

infusion every 3 weeks) and capecitabine (1250 mg/m2 twice daily for 2 weeks followed by 1-week 

rest period). 256 patients were randomised to treatment with docetaxel alone (100 mg/m2 as a 1 hour 

intravenous infusion every 3 weeks). Survival was superior in the docetaxel + capecitabine 

combination arm (p = 0.0126). Median survival was 442 days (docetaxel + capecitabine) vs. 352 days 

(docetaxel alone). The overall objective response rates in the all-randomised population (investigator 

assessment) were 41.6% (docetaxel + capecitabine) vs. 29.7% (docetaxel alone); p = 0.0058. Time to 

progressive disease was superior in the docetaxel + capecitabine combination arm (p < 0.0001). The 

median time to progression was 186 days (docetaxel + capecitabine) vs. 128 days (docetaxel alone). 

 

Non-small cell lung cancer 

 

Patients previously treated with chemotherapy with or without radiotherapy 

 

In a phase III study, in previously treated patients, time to progression (12.3 weeks versus 7 weeks) 

and overall survival were significantly longer for docetaxel at 75 mg/m² compared to Best Supportive 

Care. The 1-year survival rate was also significantly longer in docetaxel (40%) versus BSC (16%). 

There was less use of morphinic analgesic (p < 0.01), non-morphinic analgesics (p < 0.01), other 

disease-related medicinal products (p = 0.06) and radiotherapy (p < 0.01) in patients treated with 

docetaxel at 75 mg/m² compared to those with BSC.  

The overall response rate was 6.8% in the evaluable patients, and the median duration of response was 

26.1 weeks.  

 

DOCETAXEL KABI in combination with platinum agents in chemotherapy-naïve patients 

 

In a phase III study, 1218 patients with unresectable stage IIIB or IV NSCLC, with KPS of 70% or 

greater, and who did not receive previous chemotherapy for this condition, were randomised to either 

docetaxel (T) 75 mg/m2 as a 1 hour infusion immediately followed by cisplatin (Cis) 75 mg/m2 over 

30-60 minutes every 3 weeks (TCis), docetaxel 75 mg/m2 as a 1 hour infusion in combination with 

carboplatin (AUC 6 mg/ml.min) over 30-60 minutes every 3 weeks, or vinorelbine (V) 25 mg/m2 

administered over 6-10 minutes on days 1, 8, 15, 22 followed by cisplatin 100 mg/m2 administered on 

day 1 of cycles repeated every 4 weeks (VCis).  

 

Survival data, median time to progression and response rates for two arms of the study are illustrated 

in the following table:  

 

 TCis 

n = 408 

VCis 

n = 404 

Statistical analysis 

Overall survival 

(Primary end-point): 

   

Median survival (months) 11.3 10.1 Hazard Ratio: 1.122 

 [97.2% CI: 0.937; 1.342]* 

1-year Survival (%) 46 41 Treatment difference: 5.4% 

[95% CI: -1.1; 12.0] 

2 year Survival (%) 21 14 Treatment difference: 6.2% 

[95% CI: 0.2; 12.3] 

Median time to progression 

(weeks): 

22.0 23.0 Hazard Ratio: 1.032  

[95% CI: 0.876; 1.216] 

Overall response rate (%): 31.6 24.5 Treatment difference: 7.1% 

[95% CI: 0.7; 13.5] 



216 

*: Corrected for multiple comparisons and adjusted for stratification factors (stage of disease and 

region of treatment), based on evaluable patient population. 

Secondary end-points included change of pain, global rating of quality of life by EuroQoL-5D, Lung 

Cancer Symptom Scale, and changes in Karnosfky performance status. Results on these end-points 

were supportive of the primary end-points results.  

 

For docetaxel/carboplatin combination, neither equivalent nor non-inferior efficacy could be proven 

compared to the reference treatment combination VCis.  

 

Prostate cancer 

Metastatic castration-resistant prostate cancer 

 

The safety and efficacy of docetaxel in combination with prednisone or prednisolone in patients with 

metastatic castration-resistant prostate cancer were evaluated in a randomised multi-centrephase III 

study (TAX 327). A total of 1006 patients with KPS ≥ 60 were randomised to the following treatment 
groups:  

• Docetaxel 75 mg/m2 every 3 weeks for 10 cycles. 

• Docetaxel 30 mg/m2 administered weekly for the first 5 weeks in a 6 week cycle for 5 cycles. 

• Mitoxantrone 12 mg/m2 every 3 weeks for 10 cycles. 
All 3 regimens were administered in combination with prednisone or prednisolone 5 mg twice daily, 

continuously. 

 

Patients who received docetaxel every three weeks demonstrated significantly longer overall survival 

compared to those treated with mitoxantrone. The increase in survival seen in the docetaxel weekly 

arm was not statistically significant compared to the mitoxantrone control arm. Efficacy endpoints for 

the docetaxel arms versus the control arm are summarized in the following table:  

 

Endpoint 

 

Docetaxel every 3 

weeks 

Docetaxel every 

week 

Mitoxantrone 

every 3 weeks 

Number of patients 

Median survival (months) 

95% CI 

Hazard ratio 

95% CI 

p-value† * 

335 

18.9 

(17.0-21.2) 

0.761 

(0.619-0.936) 

0.0094 

334 

17.4 

(15.7-19.0) 

0.912 

(0.747-1.113) 

0.3624 

337 

16.5 

(14.4-18.6) 

- 

- 

- 

Number of patients 

PSA** response rate (%) 

95% CI 

p-value* 

291 

45.4 

(39.5-51.3) 

0.0005 

282 

47.9 

(41.9-53.9) 

< 0.0001 

300 

31.7 

(26.4-37.3) 

- 

Number of patients 

Pain response rate (%) 

95% CI 

p-value* 

153 

34.6 

(27.1-42.7) 

0.0107 

154 

31.2 

(24.0-39.1) 

0.0798 

157 

21.7 

(15.5-28.9) 

- 

Number of patients 

Tumor response rate (%) 

95% CI 

p-value* 

141 

12.1 

(7.2-18.6) 

0.1112 

134 

8.2 

(4.2-14.2) 

0.5853 

137 

6.6 

(3.0-12.1) 

- 

†Stratified log-rank test  
*Threshold for statistical significance = 0.0175  

**PSA: Prostate-Specific Antigen  

 

Given the fact that docetaxel every week presented a slightly better safety profile than docetaxel every 

3 weeks, it is possible that certain patients may benefit from docetaxel every week.  

 



217 

No statistical differences were observed between treatment groups for Global Quality of Life. 

 

Metastatic hormone-sensitive prostate cancer 

 

STAMPEDE study 

 

The safety and efficacy of docetaxel administered concomitantly with standard of care (ADT) in 

patients with high-risk locally advanced or metastatic hormone-sensitive prostate cancer were 

evaluated in a randomised multi-centre, multi-arm multi-stage (MAMS) study with a seamless phase 

II/III design (STAMPEDE – MRC PR08). A total of 1776 male patients were allocated to the 
treatment arms of interest:  

• Standard of care + docetaxel 75 mg/m², administered every 3 weeks for 6 cycles 

• Standard of care alone  

Docetaxel regimen was administered in combination with prednisone or prednisolone 5 mg twice daily 

continuously.  

Among the 1776 randomised patients 1086 (61%) had metastatic disease, 362 were randomised to 

docetaxel in combination with standard of care, 724 received standard of care alone.  

 

In these metastatic prostate cancer patients, the median overall survival was significantly longer in 

docetaxel treatment groups than in the standard of care alone group, with a median overall survival 19 

months longer with the addition of docetaxel to standard of care (HR =  0.76, 95% CI = 0.62-0.92, 

p=0.005).  

 

Efficacy results in metastatic prostate cancer patients for docetaxel arm versus control arm are 

summarized in the following table: 

 

Efficacy of docetaxel in combination with prednisone or prednisolone and standard of care in the 

treatment of patients with metastatic hormone-sensitive prostate cancer (STAMPEDE) 

 

Endpoint 

 

Docetaxel + standard of care 

 

Standard of care alone 

Number of metastatic prostate 

cancer patients 

 

Median overall survival (months)  

95% CI 

362 

 

 

62 

51-73 

724 

 

 

43 

40-48 

Adjusted hazard ratio 

95% CI 

p-valuea 

0.76 

(0.62-0.92) 

0.005 

Failure-Free survivalb    

Median (months) 

95% CI 

20.4 

16.8-25.2 

12 

9.6-12 

Adjusted hazard ratio 

95% CI 

p-valuea 

0.66 

(0.57-0.76) 

< 0.001 

a p-value calculated from the likelihood ratio test and adjusted for all stratification factors 

(except center and planned hormone therapy) and stratified by trial period 
b Failure-free survival: time from randomization to first evidence of at least one of: biochemical 

failure (defined as a rise in PSA of 50% above the within-24-week nadir and above 4 ng/mL 

and confirmed by retest or treatment); progression either locally, in lymph nodes, or in distant 

metastases; skeletal-related event; or death from prostate cancer. 

 

 



218 

CHAARTED study 

 

The safety and efficacy of docetaxel administered at the beginning of androgen-deprivation therapy 

(ADT) in patients with metastatic hormone-sensitive prostate cancer were evaluated in a randomised 

Phase III multi-centre study (CHAARTED). A total of 790 male patients were allocated to the 2 

treatment groups.  

• ADT + docetaxel 75 mg/m² given at the beginning of ADT, administered every 3 weeks 

for 6 cycles 

• ADT alone   

 

The median overall survival was significantly longer in docetaxel treatment group than in the ADT 

alone group, with a median overall survival 13.6 months longer with the addition of docetaxel to ADT 

(hazard ratio (HR) = 0.61, 95% confidence interval (CI) = 0.47-0.80, p=0.0003).  

 

Efficacy results or the docetaxel arm versus the control arm are summarized in the following table: 

 

Efficacy of docetaxel and ADT in the treatment of patients with metastatic hormone-sensitive prostate 

cancer (CHAARTED) 

 

Endpoint 

 

Docetaxel +ADT  

 

ADT alone 

Number of patients 

Median overall survival (months) 

All patients 

95% CIAdjusted hazard ratio 

397 

 

57.6 

49.1-72.8 

0.61 

393 

 

44.0 

34.4-49.1 

-- 

95% CI (0.47-0.80)  -- 

p-valuea 0.0003 -- 

Progression Free Survival 

Median (months) 

95% CI 

Adjusted hazard ratio 
95% CI 

p-value* 

 

19.8 

16.7-22.8 

0.60 

0.51-0.72 

P<0.0001 

 

11.6 

10.8-14.3 

-- 

-- 

-- 

PSA response** at 6 months – N(%) 

p-valuea* 

127 (32.0) 

<0.0001 

77 (19.6) 

-- 

PSA response** at 12 months – N(%) 

p-valuea* 

110 (27.7) 

<0.0001 

66 (16.8) 

-- 

Time to castration-resistant prostate cancerb   

Median (months)  

95% CI 

Adjusted hazard ratio 

20.2 

(17.2-23.6) 

0.61 

11.7 

(10.8-14.7) 

-- 

95% CI (0.51-0.72) -- 

p-valuea* <0.0001 -- 

Time to clinical progressionc    

Median (months)  33.0 19.8 

95% CI (27.3-41.2) (17.9-22.8) 

Adjusted hazard ratio 0.61 -- 

95% CI (0.50-0.75) -- 

p-valuea* <0.0001 -- 



219 

a Time to event variables: Stratified log-rank test.  

  Response rate variables: Fisher's Exact test  

* p-value for descriptive purpose. 

** PSA response: Prostate-Specific Antigen response: PSA level <0.2 ng/mL measured for two 

consecutive measurements at least 4 weeks apart. 

b Time to castration-resistant prostate cancer = time from randomization to PSA progression or 

clinical progression (i.e., increasing symptomatic bone metastases, progression per Response 

Evaluation Criteria in Solid Tumours (RECIST) criteria, or clinical deterioration due to cancer 

per the Investigator’s opinion), whichever occurred first. 
c The time to clinical progression = the time from randomization until clinical progression (i.e., 

increased symptoms of bone metastases; progression according to RECIST; or clinical deterioration 

due to cancer according to the investigator’s opinion). 

 

Gastric adenocarcinoma 

 

A multi-centre, open-label, randomised study, was conducted to evaluate the safety and efficacy of 
docetaxel for the treatment of patients with metastatic gastric adenocarcinoma, including 

adenocarcinoma of the gastroesophageal junction, who had not received prior chemotherapy for 

metastatic disease. A total of 445 patients with KPS > 70 were treated with either docetaxel (T) 

(75 mg/m2 on day 1) in combination with cisplatin (C) (75 mg/m2 on day 1) and 5-fluorouracil (F) 

(750 mg/m2 per day for 5 days) or cisplatin (100 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2 per 

day for 5 days). The length of a treatment cycle was 3 weeks for the TCF arm and 4 weeks for the CF 

arm. The median number of cycles administered per patient was 6 (with a range of 1-16) for the TCF 

arm compared to 4 (with a range of 1-12) for the CF arm. Time to progression (TTP) was the primary 

endpoint. The risk reduction of progression was 32.1% and was associated with a significantly longer 

TTP (p = 0.0004) in favour of the TCF arm. Overall survival was also significantly longer 

(p = 0.0201) in favour of the TCF arm with a risk reduction of mortality of 22.7%. Efficacy results are 
summarized in the following table: 

 

Efficacy of docetaxel in the treatment of patients with gastric adenocarcinoma 

 

Endpoint TCF 

n = 221 

CF 

n = 224 

Median TTP (months) 

(95% CI) 

Hazard ratio 

(95% CI) 

*p-value 

5.6 

(4.86-5.91) 

3.7 

(3.45-4.47) 

1.473 

(1.189-1.825) 

0.0004 

Median survival (months) 

(95% CI) 

2-year estimate (%) 

Hazard ratio 

(95% CI) 

*p-value 

9.2 

(8.38-10.58) 

18.4 

8.6 

(7.16-9.46) 

8.8 

1.293 

(1.041-1.606) 

0.0201 

Overall Response Rate (CR+PR) (%) 

p-value 

36.7 25.4 

0.0106 

Progressive Disease as Best Overall Response (%) 16.7 25.9 

*Unstratified logrank test  

 

Subgroup analyses across age, gender and race consistently favoured the TCF arm compared to the 
CF arm.  



220 

 

A survival update analysis conducted with a median follow-up time of 41.6 months no longer showed 

a statistically significant difference although always in favour of the TCF regimen and showed that the 

benefit of TCF over CF is clearly observed between 18 and 30 months of follow up.  

 

Overall, quality of life (QoL) and clinical benefit results consistently indicated improvement in favour 
of the TCF arm. Patients treated with TCF had a longer time to 5% definitive deterioration of global 

health status on the QLQ-C30 questionnaire (p = 0.0121) and a longer time to definitive worsening of 

Karnofsky performance status (p = 0.0088) compared to patients treated with CF. 

 

Head and neck cancer 

 

• Induction chemotherapy followed by radiotherapy (TAX323)  
The safety and efficacy of docetaxel in the induction treatment of patients with squamous cell 

carcinoma of the head and neck (SCCHN) was evaluated in a phase III, multi-centre, open-label, 

randomised study (TAX323). In this study, 358 patients with inoperable locally advanced SCCHN, 

and WHO performance status 0 or 1, were randomised to one of two treatment arms. Patients on the 
docetaxel arm received docetaxel (T) 75 mg/m2 followed by cisplatin (P) 75 mg/m2 followed by 

5-fluorouracil (F) 750 mg/m2 per day as a continuous infusion for 5 days. This regimen was 

administered every three weeks for 4 cycles in case at least a minor response (≥ 25% reduction in 

bidimensionally measured tumour size) was observed after 2 cycles. At the end of chemotherapy, with 

a minimal interval of 4 weeks and a maximal interval of 7 weeks, patients whose disease did not 

progress received radiotherapy (RT) according to institutional guidelines for 7 weeks (TPF/RT). 

Patients on the comparator arm received cisplatin (P) 100 mg/m2 followed by 5-fluorouracil (F) 

1000 mg/m2 per day for 5 days. This regimen was administered every three weeks for 4 cycles in case 

at least a minor response (≥ 25% reduction in bidimensionally measured tumour size) was observed 

after 2 cycles. At the end of chemotherapy, with a minimal interval of 4 weeks and a maximal interval 

of 7 weeks, patients whose disease did not progress received radiotherapy (RT) according to 

institutional guidelines for 7 weeks (PF/RT). Locoregional therapy with radiation was delivered either 

with a conventional fraction (1.8 Gy - 2.0 Gy once a day, 5 days per week for a total dose of 66 to 

70 Gy), or accelerated/hyperfractionated regimens of radiation therapy (twice a day, with a minimum 

interfraction interval of 6 hours, 5 days per week). A total of 70 Gy was recommended for accelerated 

regimens and 74 Gy for hyperfractionated schemes. Surgical resection was allowed following 

chemotherapy, before or after radiotherapy. Patients on the TPF arm received antibiotic prophylaxis 

with ciprofloxacin 500 mg orally twice daily for 10 days starting on day 5 of each cycle, or equivalent. 

The primary endpoint in this study, progression-free survival (PFS), was significantly longer in the 

TPF arm compared to the PF arm, p = 0.0042 (median PFS: 11.4 vs. 8.3 months respectively) with an 

overall median follow up time of 33.7 months. Median overall survival was also significantly longer in 

favour of the TPF arm compared to the PF arm (median OS: 18.6 vs. 14.5 months respectively) with a 
28% risk reduction of mortality, p = 0.0128. Efficacy results are presented in the table below:  

 

Efficacy of docetaxel in the induction treatment of patients with inoperable locally advanced SCCHN 

(Intent-to-Treat Analysis) 

 

Endpoint Docetaxel + 

Cis + 5-FU 

n = 177 

Cis + 5-FU 

 

n = 181 

Median progression free survival (months) 

(95% CI) 

Adjusted Hazard ratio 

(95% CI) 

*p-value 

11.4 

(10.1-14.0) 

8.3 

(7.4-9.1) 

0.70 

(0.55-0.89) 

0.0042 

Median survival (months) 

(95% CI) 

18.6 

(15.7-24.0) 

14.5 

(11.6-18.7) 



221 

Endpoint Docetaxel + 

Cis + 5-FU 

n = 177 

Cis + 5-FU 

 

n = 181 

Hazard ratio 

(95% CI) 

**p-value 

0.72 

(0.56-0.93) 

0.0128 

Best overall response to chemotherapy (%) 

(95% CI)  

***p-value 

67.8 

(60.4-74.6) 

53.6 

(46.0-61.0) 

0.006 

Best overall response to study treatment [chemotherapy 

+/- radiotherapy] (%) 

(95% CI)  

***p-value 

72.3 

(65.1-78.8) 

58.6 

(51.0-65.8) 

0.006 

 Median duration of response to chemotherapy ± 

radiotherapy (months) 

(95% CI)  

Hazard ratio 

(95% CI) 

**p-value 

n = 128 

15.7 

(13.4-24.6) 

n = 106 

11.7 

(10.2-17.4) 

0.72 

(0.52-0.99) 

0.0457 

A hazard ratio of less than 1 favours docetaxel + cisplatin + 5-FU 
*Cox model (adjustment for Primary tumour site, T and N clinical stages and PSWHO) 

**Logrank test  

*** Chi-square test  

 

Quality of life parameters 

 

Patients treated with TPF experienced significantly less deterioration of their Global health score 

compared to those treated with PF (p = 0.01, using the EORTC QLQ-C30 scale). 

 

Clinical benefit parameters 

 

The performance status scale, for head and neck (PSS-HN) subscales designed to measure 

understandability of speech, ability to eat in public, and normalcy of diet, was significantly in favour 
of TPF as compared to PF. 

Median time to first deterioration of WHO performance status was significantly longer in the TPF arm 

compared to PF. Pain intensity score improved during treatment in both groups indicating adequate 

pain management.  

 

• Induction chemotherapy followed by chemoradiotherapy (TAX324)  
The safety and efficacy of docetaxel in the induction treatment of patients with locally advanced 

squamous cell carcinoma of the head and neck (SCCHN) was evaluated in a randomised, multi-

centre open-label, phase III, study (TAX324). In this study, 501 patients, with locally advanced 

SCCHN, and a WHO performance status of 0 or 1, were randomised to one of two arms. The study 
population comprised patients with technically unresectable disease, patients with low probability of 

surgical cure and patients aiming at organ preservation. The efficacy and safety evaluation solely 

addressed survival endpoints and the success of organ preservation was not formally addressed. 

Patients on the docetaxel arm received docetaxel (T) 75 mg/m² by intravenous infusion on day 1 

followed by cisplatin (P) 100 mg/m² administered as a 30-minute to three-hour intravenous infusion, 

followed by the continuous intravenous infusion of 5-fluorouracil (F) 1000 mg/m²/day from day 1 to 

day 4. The cycles were repeated every 3 weeks for 3 cycles. All patients who did not have progressive 

disease were to receive chemoradiotherapy (CRT) as per protocol (TPF/CRT). Patients on the 

comparator arm received cisplatin (P) 100 mg/m² as a 30-minute to three-hour intravenous infusion on 

day 1 followed by the continuous intravenous infusion of 5-fluorouracil (F) 1000 mg/m²/day from day 



222 

1 to day 5. The cycles were repeated every 3 weeks for 3 cycles. All patients who did not have 

progressive disease were to receive CRT as per protocol (PF/CRT).  

Patients in both treatment arms were to receive 7 weeks of CRT following induction chemotherapy 

with a minimum interval of 3 weeks and no later than 8 weeks after start of the last cycle (day 22 to 

day 56 of last cycle). During radiotherapy, carboplatin (AUC 1.5) was given weekly as a one-hour 

intravenous infusion for a maximum of 7 doses. Radiation was delivered with megavoltage equipment 

using once daily fractionation (2 Gy per day, 5 days per week for 7 weeks, for a total dose of 

70-72 Gy). Surgery on the primary site of disease and/or neck could be considered at anytime 

following completion of CRT. All patients on the docetaxel-containing arm of the study received 

prophylactic antibiotics. The primary efficacy endpoint in this study, overall survival (OS) was 

significantly longer (log-rank test, p = 0.0058) with the docetaxel-containing regimen compared to PF 

(median OS: 70.6 versus 30.1 months respectively), with a 30% risk reduction in mortality compared 

to PF (hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.54-0.90) with an overall median 

follow up time of 41.9 months. The secondary endpoint, PFS, demonstrated a 29% risk reduction of 

progression or death and a 22 month improvement in median PFS (35.5 months for TPF and 13.1 for 

PF). This was also statistically significant with an HR of 0.71; 95% CI 0.56-0.90; log-rank test 

p = 0.004. Efficacy results are presented in the table below: 

 

Efficacy of docetaxel in the induction treatment of patients with locally advanced SCCHN (Intent-to-

Treat Analysis) 

 

Endpoint Docetaxel + Cis + 5-FU 

n = 255 

Cis + 5-FU 

n = 246 

Median overall survival (months) 

(95% CI) 

Hazard ratio: 

(95% CI) 

*p-value  

70.6 

(49.0-NA) 

30.1 

(20.9-51.5) 

0.70 

(0.54-0.90) 

0.0058 

Median PFS (months) 

(95% CI) 

Hazard ratio: 

(95% CI) 

**p-value  

35.5 

(19.3-NA) 

13.1 

(10.6-20.2) 

0.71 

(0.56 - 0.90) 

0.004 

Best overall response (CR + PR) to 

chemotherapy (%) 

(95% CI)  

***p-value 

71.8 

(65.8-77.2) 

64.2 

(57.9-70.2) 

0.070 

Best overall response (CR + PR) to study 

treatment [chemotherapy +/- 

chemoradiotherapy] (%) 

(95% CI) 

***p-value 

 

76.5 

(70.8-81.5) 

 

71.5 

(65.5-77.1) 

0.209 

A hazard ratio of less than 1 favoursdocetaxel + cisplatin + fluorouracil  
*un-adjusted log-rank test  

**un-adjusted log-rank test, not adjusted for multiple comparisons  

***Chi square test, not adjusted for multiple comparisons  

NA-not applicable 

 

 

 

 

 

 



223 

5.2 Pharmacokinetic properties 

 

Absorption 

 

The pharmacokinetics of docetaxel have been evaluated in cancer patients after administration of 20-

115 mg/m2 in phase I studies. The kinetic profile of docetaxel is dose independent and consistent with 

a three-compartment pharmacokinetic model with half lives for the α, β and γ phases of 4 min, 36 min 

and 11.1 h, respectively. The late phase is due, in part, to a relatively slow efflux of docetaxel from the 

peripheral compartment. 

 

Distribution 

 

Following the administration of a 100 mg/m2 dose given as a one-hour infusion a mean peak plasma 

level of 3.7 μg/ml was obtained with a corresponding AUC of 4.6 h.μg/ml. Mean values for total body 

clearance and steady-state volume of distribution were 21 l/h/m2 and 113 l, respectively. Inter 

individual variation in total body clearance was approximately 50%. Docetaxel is more than 95% 

bound to plasma proteins. 

 

Elimination 

 

A study of 14C-docetaxel has been conducted in three cancer patients. Docetaxel was eliminated in 

both the urine and faeces following cytochrome P450-mediated oxidative metabolism of the tert-butyl 

ester group, within seven days, the urinary and faecal excretion accounted for about 6% and 75% of 

the administered radioactivity, respectively. About 80% of the radioactivity recovered in faeces is 

excreted during the first 48 hours as one major inactive metabolite and 3 minor inactive metabolites 

and very low amounts of unchanged medicinal product.  

 

Special populations 

 

Age and gender 

A population pharmacokinetic analysis has been performed with docetaxel in 577 patients. 

Pharmacokinetic parameters estimated by the model were very close to those estimated from phase I 

studies. The pharmacokinetics of docetaxel were not altered by the age or sex of the patient. 

 

Hepatic impairment 

In a small number of patients (n = 23) with clinical chemistry data suggestive of mild to moderate liver 

function impairment (ALT, AST ≥ 1.5 times the ULN associated with alkaline phosphatase ≥ 2.5 

times the ULN), total clearance was lowered by 27% on average (see section 4.2). 

 

Fluid retention 

Docetaxel clearance was not modified in patients with mild to moderate fluid retention and there are 

no data available in patients with severe fluid retention. 

 

Combination therapy 

 

Doxorubicin 

When used in combination, docetaxel does not influence the clearance of doxorubicin and the plasma 

levels of doxorubicinol (a doxorubicin metabolite). The pharmacokinetics of docetaxel, doxorubicin 

and cyclophosphamide were not influenced by their co-administration.  

 

Capecitabine 

Phase I study evaluating the effect of capecitabine on the pharmacokinetics of docetaxel and vice versa 

showed no effect by capecitabine on the pharmacokinetics of docetaxel (Cmax and AUC) and no 

effect by docetaxel on the pharmacokinetics of a relevant capecitabine metabolite 5'-DFUR.  

 

 

 



224 

Cisplatin 

Clearance of docetaxel in combination therapy with cisplatin was similar to that observed following 

monotherapy. The pharmacokinetic profile of cisplatin administered shortly after docetaxel infusion is 

similar to that observed with cisplatin alone.  

 

Cisplatin and 5-fluorouracil 

The combined administration of docetaxel, cisplatin and 5-fluorouracil in 12 patients with solid 

tumours had no influence on the pharmacokinetics of each individual medicinal product.  

 

Prednisone and dexamethasone 

The effect of prednisone on the pharmacokinetics of docetaxel administered with standard 

dexamethasone premedication has been studied in 42 patients. 

 

Prednisone 

No effect of prednisone on the pharmacokinetics of docetaxel was observed. 

 

 

5.3  Preclinical safety data 

 

The carcinogenic potential of docetaxel has not been studied. 

Docetaxel has been shown to be mutagenic in the in vitro micronucleus and chromosome aberration 

test in CHO-K1 cells and in the in vivo micronucleus test in the mouse. However, it did not induce 

mutagenicity in the Ames test or the CHO/HGPRT gene mutation assay. These results are consistent 

with the pharmacological activity of docetaxel.  

 

It was shown that docetaxel was embryotoxic and fetotoxic in rats and rabbits. Undesirable effects on 

the testis observed in rodent toxicity studies suggest that docetaxel may impair male fertility. 

 

 

6. PHARMACEUTICAL PARTICULARS 
 

6.1 List of excipients 

 

Polysorbate 80 

Ethanol anhydrous 

Anhydrous citric acid (pH adjustment) 

 

 

6.2 Incompatibilities 

 

This medicinal product must not be mixed with other medicinal products except those mentioned in 

section 6.6. 

 

 

6.3 Shelf life 

 

Unopened vial 

2 years. 

 

After opening of the vial 

Each vial is for single use and should be used immediately after opening. If not used immediately, 

in-use storage times and conditions are the responsibility of the user. 

 

Once added to the infusion bag 

From a microbiological point of view, reconstitution/dilution must take place in controlled and aseptic 

conditions and the medicinal product should be used immediately. If not used immediately, in-use 

storage times and conditions are the responsibility of the user. 



225 

 

Once added as recommended into the infusion bag, the docetaxel infusion solution, if stored below 

25°C, is stable for 6 hours. It should be used within 6 hours (including the one hour infusion 

intravenous administration). 

 

In addition, physical and chemical in-use stability of the infusion solution prepared as recommended 

has been demonstrated in non-PVC bags up to 48 hours when stored between 2 to 8°C. 

 

 

6.4 Special precautions for storage 

 

Do not store above 25°C.  

Store in the original package in order to protect from light.  

 

For storage conditions of the diluted medicinal product, see section 6.3. 

 

 

6.5 Nature and contents of container 

 

10 ml clear, colourless Type-I glass vial, closed with flurotec rubber stopper and a orange flip-off 

aluminium over seal containing 9 ml of concentrate. 

 

Each box contains one vial. 

 

 

6.6 Special precautions for disposal and other handling 

 

DOCETAXEL KABI is an antineoplastic agent and, as with other potentially toxic compounds, 

caution should be exercised when handling it and preparing the solution. The use of gloves is 

recommended. 

 

If DOCETAXEL KABI concentrate or infusion solution should come into contact with skin, wash 

immediately and thoroughly with soap and water. If DOCETAXEL KABI concentrate or infusion 

solution should come into contact with mucous membranes, wash immediately and thoroughly with 

water. 

 

Preparation for the intravenous administration 
 

Preparation of the infusion solution 

DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 

with this medicinal product (DOCETAXEL KABI 180 mg/9 ml concentrate for solution for 

infusion, which contains only 1 vial). 

 

DOCETAXEL KABI 180 mg/9 ml concentrate for solution for infusion requires NO prior 

dilution with a solvent and is ready to add to the infusion solution. 

 

Each vial is for single use and should be used immediately. 

 

If the vials are stored under refrigeration, allow the required number of boxes of DOCETAXEL KABI 

concentrate for solution for infusion to stand below 25°C for 5 minutes before use. More than one vial 

of DOCETAXEL KABI concentrate for solution for infusion may be necessary to obtain the required 

dose for the patient. Aseptically withdraw the required amount of DOCETAXEL KABI concentrate 

for solution for infusion using a calibrated syringe.  

 

In DOCETAXEL KABI 180 mg/9 ml vial the concentration of docetaxel is 20 mg/ml. 



226 

The required volume of DOCETAXEL KABI concentrate for solution for infusion must be injected 

via a single injection (one shot) into a 250 ml infusion bag or bottle containing either 5% glucose 

solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. 

 

If a dose greater than 190 mg of docetaxel is required, use a larger volume of the infusion vehicle so 

that a concentration of 0.74 mg/ml docetaxel is not exceeded. 

 

Mix the infusion bag or bottle manually using a rocking motion. 

 

The infusion bag solution should be used within 6 hours below 25°C including the one hour infusion 

to the patient. 

 

As with all parenteral products, DOCETAXEL KABI infusion solution should be visually inspected 

prior to use, and solutions containing a precipitate should be discarded. 

 

Docetaxel infusion solution is supersaturated, therefore may crystallize over time. If crystals appear, 

the solution must no longer be used and shall be discarded. 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Fresenius Kabi Deutschland GmbH 

Else-Kröner-Straße 1, 

61352 Bad Homburg v.d.Höhe 

Germany 

 

 

8. MARKETING AUTHORISATION NUMBER 
 

EU/1/12/770/004 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 22nd May 2012 

Date of latest renewal: 23 February 2017 

 

 

10. DATE OF REVISION OF THE TEXT 
 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu  



227 

 
 

 
 

 
 

 
 

 

 
 

 
 

 
 

 
 

 

 
ANNEX II 

 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 



228 

A.  MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 

Name and address of the manufacturers responsible for batch release 

 

Fresenius Kabi Deutschland GmbH 

Pfingstweide 53 

61169 Friedberg 

Germany  

 

Or 

 

Fresenius Kabi Oncology Plc 

Lion Court 

Farnham Road, Bordon 

Hampshire, GU35 0NF 

United Kingdom 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch. 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 

Characteristics, section 4.2). 

 

 

C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  

 

•  Periodic Safety Update Reports (PSURs) 
 

The requirements for submission of PSUR for this medicinal product are set out in the list of 

Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 

and any subsequent updates published on the European medicines web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 

        USE OF THE MEDICINAL PRODUCT 

 

• Risk management plan (RMP) 
 

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 

activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 

Marketing Authorisation and any agreed subsequent updates of the RMP. 

 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of  
new information being received that may lead to a significant change to the  

benefit/risk profile or as the result of an important (pharmacovigilance or risk 

minimisation) milestone being reached. 

 

 

 



229 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 



230 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 



231 

PARTICULARS TO APPEAR ON OUTER PACKAGING 

 

OUTER CARTON  

 

1. NAME OF THE MEDICINAL PRODUCT 

 

DOCETAXEL KABI 20 mg/1 ml concentrate for solution for infusion 

 

docetaxel 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each ml of concentrate contains 20 mg docetaxel anhydrous. 

One vial of 1 ml of concentrate contains 20 mg of docetaxel. 

 

3. LIST OF EXCIPIENTS 

 

Excipients: polysorbate 80, ethanol anhydrous (see leaflet for further information), anhydrous citric 

acid (for pH adjustment).  
 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Concentrate for solution for infusion  

 

1 vial with 20 mg/1 ml 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Ready to add to infusion solution. 

 

Read the package leaflet before use. 

Intravenous use 

Single-use vial. 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

Cytotoxic 

 

8. EXPIRY DATE 

 

Exp: 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C.  

Store in the original package in order to protect from light. 

 

 



232 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

 

Fresenius Kabi Deutschland GmbH 

Else-Kröner-Straße 1, 

61352 Bad Homburg v.d.Höhe 

Germany 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/12/770/005 

 

13. BATCH NUMBER 

 

Lot: 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC:  

SN:  

NN:  

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 



233 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

DOCETAXEL KABI 20 mg/1 ml concentrate for solution for infusion 

 

docetaxel 

 

Intravenous use. 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

Exp:  

 

4. BATCH NUMBER 

 

Lot: 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

20 mg/1 ml  

 

6. OTHER 

 

Cytotoxic 



234 

PARTICULARS TO APPEAR ON OUTER PACKAGING 

 

OUTER CARTON  

 

1. NAME OF THE MEDICINAL PRODUCT 

 

DOCETAXEL KABI 80 mg/4 ml concentrate for solution for infusion 

 

docetaxel 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each ml of concentrate contains 20 mg docetaxel anhydrous. 

One vial of 4 ml of concentrate contains 80 mg of docetaxel. 

 

3. LIST OF EXCIPIENTS 

 

Excipients: polysorbate 80, ethanol anhydrous (see leaflet for further information), anhydrous citric 

acid (for pH adjustment).  

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Concentrate for solution for infusion  

 

1 vial with 80 mg/4 ml 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Ready to add to infusion solution. 

 

Read the package leaflet before use. 

Intravenous use 

Single-use vial. 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

Cytotoxic 

 

8. EXPIRY DATE 

 

Exp: 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C.  

Store in the original package in order to protect from light. 

 



235 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Fresenius Kabi Deutschland GmbH 

Else-Kröner-Straße 1, 

61352 Bad Homburg v.d.Höhe 

Germany 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/12/770/001 

 

13. BATCH NUMBER 

 

Lot: 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC:  

SN:  

NN:  



236 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

DOCETAXEL KABI 80 mg/4 ml concentrate for solution for infusion 

 

docetaxel 

 

Intravenous use. 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

Exp:  

 

4. BATCH NUMBER 

 

Lot: 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

80 mg/4 ml  

 

6. OTHER 

 

Cytotoxic 



237 

PARTICULARS TO APPEAR ON OUTER PACKAGING 

 

OUTER CARTON  

 

1. NAME OF THE MEDICINAL PRODUCT 

 

DOCETAXEL KABI 120 mg/6 ml concentrate for solution for infusion 

 

docetaxel 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each ml of concentrate contains 20 mg docetaxel anhydrous. 

One vial of 6 ml of concentrate contains 120 mg of docetaxel. 

 

3. LIST OF EXCIPIENTS 

 

Excipients: polysorbate 80, ethanol anhydrous (see leaflet for further information), anhydrous citric 

acid (for pH adjustment).  

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Concentrate for solution for infusion  

 

1 vial with 120 mg/6 ml 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Ready to add to infusion solution. 

 

Read the package leaflet before use. 

Intravenous use 

Single-use vial. 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

Cytotoxic 

 

8. EXPIRY DATE 

 

Exp: 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C.  

Store in the original package in order to protect from light. 

 

 



238 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

 

Fresenius Kabi Deutschland GmbH 

Else-Kröner-Straße 1, 

61352 Bad Homburg v.d.Höhe 

Germany 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/12/770/002 

 

13. BATCH NUMBER 

 

Lot: 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC:  

SN:  

NN:  

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 



239 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

DOCETAXEL KABI 120 mg/6 ml concentrate for solution for infusion 

 

docetaxel 

 

Intravenous use. 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

Exp:  

 

4. BATCH NUMBER 

 

Lot: 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

120 mg/6 ml  

 

6. OTHER 

 

Cytotoxic 



240 

PARTICULARS TO APPEAR ON OUTER PACKAGING 

 

OUTER CARTON  

 

1. NAME OF THE MEDICINAL PRODUCT 

 

DOCETAXEL KABI 160 mg/8 ml concentrate for solution for infusion 

 

docetaxel 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each ml of concentrate contains 20 mg docetaxel anhydrous. 

One vial of 8 ml of concentrate contains 160 mg of docetaxel. 

 

3. LIST OF EXCIPIENTS 

 

Excipients: polysorbate 80, ethanol anhydrous (see leaflet for further information), anhydrous citric 

acid (for pH adjustment).  

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Concentrate for solution for infusion  

 

1 vial with 160 mg/8 ml 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Ready to add to infusion solution. 

 

Read the package leaflet before use. 

Intravenous use 

Single-use vial. 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

Cytotoxic 

 

8. EXPIRY DATE 

 

Exp: 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C.  

Store in the original package in order to protect from light. 

 



241 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Fresenius Kabi Deutschland GmbH 

Else-Kröner-Straße 1, 

61352 Bad Homburg v.d.Höhe 

Germany 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/12/770/003 

 

13. BATCH NUMBER 

 

Lot: 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN:  

NN:  



242 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

DOCETAXEL KABI 160 mg/8 ml concentrate for solution for infusion 

 

docetaxel 

 

Intravenous use. 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

Exp:  

 

4. BATCH NUMBER 

 

Lot: 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

160 mg/8 ml  

 

6. OTHER 

 

Cytotoxic 



243 

PARTICULARS TO APPEAR ON OUTER PACKAGING 

 

OUTER CARTON  

 

1. NAME OF THE MEDICINAL PRODUCT 

 

DOCETAXEL KABI 180 mg/9 ml concentrate for solution for infusion 

 

docetaxel 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each ml of concentrate contains 20 mg docetaxel anhydrous. 

One vial of 9 ml of concentrate contains 180 mg of docetaxel. 

 

3. LIST OF EXCIPIENTS 

 

Excipients: polysorbate 80, ethanol anhydrous (see leaflet for further information), anhydrous citric 

acid (for pH adjustment). 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Concentrate for solution for infusion  

 

1 vial with 180 mg/9 ml 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Ready to add to infusion solution. 

 

Read the package leaflet before use. 

Intravenous use 

Single-use vial. 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

Cytotoxic 

 

8. EXPIRY DATE 

 

Exp: 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C.  

Store in the original package in order to protect from light. 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 



244 

 

 

 

Fresenius Kabi Deutschland GmbH 

Else-Kröner-Straße 1, 

61352 Bad Homburg v.d.Höhe 

Germany 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/12/770/004 

 

13. BATCH NUMBER 

 

Lot: 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN:  

NN:  

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 



245 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

DOCETAXEL KABI 180 mg/9 ml concentrate for solution for infusion 

 

docetaxel 

 

Intravenous use. 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

Exp:  

 

4. BATCH NUMBER 

 

Lot: 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

180 mg/9 ml  

 

6. OTHER 

 

Cytotoxic 



246 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



247 

Package leaflet: Information for the patient 

 

DOCETAXEL KABI 20 mg/1 ml concentrate for solution for infusion 

docetaxel 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor, hospital pharmacist or nurse. 

- If you get any side effects, talk to your doctor, hospital pharmacist or nurse. This includes any 
 possible side effects not listed in this leaflet. See section 4. 

 

What is in this leaflet: 

 

1. What DOCETAXEL KABI is and what it is used for 

2.  What you need to know before you use DOCETAXEL KABI 

3.  How to use DOCETAXEL KABI 

4.  Possible side effects 

5.  How to store DOCETAXEL KABI 

6.  Contents of the pack and other information 

 

 

1. What DOCETAXEL KABI is and what it is used for 
 

The name of this medicine is DOCETAXEL KABI. Its common name is docetaxel. Docetaxel is a 

substance derived from the needles of yew trees. 

Docetaxel belongs to the group of anti-cancer medicines called taxoids. 

 

DOCETAXEL KABI has been prescribed by your doctor for the treatment of breast cancer, special 

forms of lung cancer (non-small cell lung cancer), prostate cancer, gastric cancer or head and neck 

cancer: 

- For the treatment of advanced breast cancer, DOCETAXEL KABI could be administered either 
alone or in combination with doxorubicin, or trastuzumab, or capecitabine. 

- For the treatment of early breast cancer with or without lymph node involvement, DOCETAXEL 
KABI could be administered in combination with doxorubicin and cyclophosphamide. 

- For the treatment of lung cancer, DOCETAXEL KABI could be administered either alone or in 
combination with cisplatin. 

- For the treatment of prostate cancer, DOCETAXEL KABI is administered in combination with 
prednisone or prednisolone. 

- For the treatment of metastatic gastric cancer, DOCETAXEL KABI is administered in 
combination with cisplatin and 5-fluorouracil. 

- For the treatment of head and neck cancer, DOCETAXEL KABI is administered in combination 
with cisplatin and 5-fluorouracil. 

 

 

2. What you need to know before you use DOCETAXEL KABI  
 

You must not be given DOCETAXEL KABI: 

 

• if you are allergic (hypersensitive) to docetaxel or any of the other ingredients of DOCETAXEL 
KABI (listed in section 6). 

• if the number of white blood cells is too low. 

• if you have a severe liver disease. 



248 

Warnings and precautions 

 

Before each treatment with DOCETAXEL KABI, you will have blood tests to check that you have 

enough blood cells and sufficient liver function to receive DOCETAXEL KABI. In case of white 

blood cells disturbances, you may experience associated fever or infections. 

 

Tell your doctor, hospital pharmacist, or nurse immediately if you have abdominal pain or tenderness, 

diarrhoea, rectal haemorrhage, blood in stool or fever. These symptoms may be the first signs of a 

serious gastrointestinal toxicity, which could be fatal. Your doctor should address them immediately. 

 

Tell your doctor, hospital pharmacist or nurse if you have vision problems. In case of vision problems, 

in particular blurred vision, you should immediately have your eyes and vision examined.  

 

Tell your doctor, hospital pharmacist or nurse if you have experienced an allergic reaction to previous 

paclitaxel therapy. 

 

Tell your doctor, hospital pharmacist or nurse if you have heart problems.  

 

If you develop acute or worsening problems with your lungs (fever, shortness of breath or cough), 

please tell your doctor, hospital pharmacist or nurse immediately. Your doctor may stop your 

treatment immediately. 

 

You will be asked to take premedication consisting of an oral corticosteroid such as dexamethasone, 

one day prior to DOCETAXEL KABI administration and to continue for one or two days after it in 

order to minimise certain undesirable effects which may occur after the infusion of DOCETAXEL 

KABI in particular allergic reactions and fluid retention (swelling of the hands, feet, legs or weight 

gain). 

 

During treatment, you may be given other medicines to maintain the number of your blood cells. 

 

Severe skin problems such as Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), 

Acute Generalized Exanthematous Pustulosis (AGEP) have been reported with DOCETAXEL KABI:  

- SJS/TEN symptoms may include blistering, peeling or bleeding on any part of your skin 
(including your lips, eyes, mouth, nose, genitals, hands or feet) with or without a rash. You 

may also have flu-like symptoms at the same time, such as fever, chills or aching muscles. 

- AGEP symptoms may include a red, scaly widespread rash with bumps under the swollen skin 
(including your skin folds, trunk, and upper extremities) and blisters accompanied by fever.  

If you develop severe skin reactions or any of the reactions listed above, immediately contact your 

doctor or healthcare professional. 

 

DOCETAXEL KABI contains alcohol. Discuss with your doctor if you suffer from alcohol 

dependency, epilepsy or liver impairment. See also section “DOCETAXEL KABI contains ethanol 

(alcohol)” below.  

 

Other medicines and DOCETAXEL KABI 
 

Please tell your doctor or hospital pharmacist if you are taking or have recently taken any other 

medicine, including medicines obtained without a prescription. This is because DOCETAXEL KABI 

or the other medicine may not work as well as expected and you may be more likely to get a side 

effect. The amount of alcohol in this medicinal product may alter the effects of other medicines. 

 

Pregnancy, breast-feeding and fertility 

 

Ask your doctor for advice before being given any medicine. 

 

DOCETAXEL KABI must NOT be administered if you are pregnant unless clearly indicated by your 

doctor. 



249 

 

You must not become pregnant during treatment with this medicine and must use an effective method 

of contraception during therapy, because DOCETAXEL KABI may be harmful for the unborn baby. If 

pregnancy occurs during your treatment, you must immediately inform your doctor. 

 

You must not breast-feed while you are treated with DOCETAXEL KABI. 

 

If you are a man being treated with DOCETAXEL KABI you are advised not to father a child during 

and up to 6 months after treatment and to seek advice on conservation of sperm prior to treatment 

because docetaxel may alter male fertility. 

 

Driving and using machines 

 

The amount of alcohol in this medicinal product may impair your ability to drive or use machines. 

You may experience side effects of this medicine that may impair your ability to drive, use tools or 

operate machines (see section 4 Possible side effects). If this happens, do not drive or use any tools or 

machines before discussing with your doctor, nurse or hospital pharmacist. 

 

DOCETAXEL KABI contains ethanol (alcohol). 

 

This medicine contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 395 mg ethanol anhydrous per 

vial, equivalent to 10 ml of beer or 4 ml wine. 

Harmful for those suffering from alcoholism. 

To be taken into account in pregnant or breast-feeding women, in children and high-risk groups such 

as patients with liver disease, or epilepsy. 

 

The amount of alcohol in this medicine may have effects on the central nervous system (the part of the 

nervous system that includes the brain and spinal cord). 

 

 

3. How to use DOCETAXEL KABI  
 

DOCETAXEL KABI will be administered to you by a healthcare professional. 

 

Usual dose 

 

The dose will depend on your weight and your general condition. Your doctor will calculate your body 

surface area in square meters (m²) and will determine the dose you should receive. 

 

Method and route of administration 

 

DOCETAXEL KABI will be given by infusion into one of your veins (intravenous use). The infusion 

will last approximately one hour during which you will be in the hospital. 

 

Frequency of administration 

 

You should usually receive your infusion once every 3 weeks. 

 

Your doctor may change the dose and frequency of dosing depending on your blood tests, your general 

condition and your response to DOCETAXEL KABI. In particular, please inform your doctor in case 

of diarrhoea, sores in the mouth, feeling of numbness or pins and needles, fever and give her/him 

results of your blood tests. Such information will allow her/him to decide whether a dose reduction is 

needed. If you have any further questions on the use of this medicine, ask your doctor, or hospital 

pharmacist. 

 

 

 



250 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Your doctor will discuss these with you and will explain the potential risks and benefits of your 

treatment. 

 

The most commonly reported adverse reactions of DOCETAXEL KABI alone are: decrease in the 

number of red blood cells or white blood cells, alopecia, nausea, vomiting, sores in the mouth, 

diarrhoea and tiredness. 

 

The severity of adverse events of DOCETAXEL KABI may be increased when DOCETAXEL KABI 

is given in combination with other chemotherapeutic agents. 

 

During the infusion at the hospital the following allergic reactions may occur (may affect more than 1 

in 10 people): 

• flushing, skin reactions, itching 

• chest tightness; difficulty in breathing 

• fever or chills 

• back pain 

• low blood pressure. 
More severe reactions may occur. 

If you had an allergic reaction to paclitaxel, you may also experience an allergic reaction to docetaxel, 

which may be more severe. 

 

The hospital staff will monitor your condition closely during treatment. Tell them immediately if you 

notice any of these effects. 

 

Between infusions of DOCETAXEL KABI the following may occur, and the frequency may vary with 

the combinations of medicines that are received 

 

Very common (may affect more than 1 in 10 people): 

• infections, decrease in the number of red (anaemia), or white blood cells (which are important in 
fighting infection) and platelets 

• fever: if this happens you must tell your doctor immediately 

• allergic reactions as described above 

• loss of appetite (anorexia) 

• insomnia 

• feeling of numbness or pins and needles or pain in the joints or muscles 

• headache 

• alteration in sense of taste 

• inflammation of the eye or increased tearing of the eyes 

• swelling caused by faulty lymphatic drainage 

• shortness of breath 

• nasal drainage; inflammation of the throat and nose; cough 

• bleeding from the nose 

• sores in the mouth 

• stomach upsets including nausea, vomiting and diarrhoea, constipation 

• abdominal pain 

• indigestion 

• hair loss: in most cases normal hair growth should return. In some cases (frequency not known) 
permanent hair loss has been observed 

• redness and swelling of the palms of your hands or soles of your feet which may cause your skin to 
peel (this may also occur on the arms, face, or body) 

• change in the colour of your nails, which may detach 



251 

• muscle aches and pains; back pain or bone pain 

• change or absence of menstrual period 

• swelling of the hands, feet, legs 

• tiredness; or flu-like symptoms 

• weight gain or loss. 

• infection of the upper respiratory tract. 
 

Common (may affect up to 1 in 10 people): 

• oral candidiasis 

• dehydration 

• dizziness 

• hearing impaired 

• decrease in blood pressure; irregular or rapid heart beat 

• heart failure 

• oesophagitis 

• dry mouth 

• difficulty or painful swallowing 

• haemorrhage 

• raised liver enzymes (hence the need for regular blood tests). 

• rises in blood sugar levels (diabetes) 

• decrease of the potassium, calcium and/or phosphate in your blood.  
 

Uncommon (may affect up to 1 in 100 people): 

• fainting 

• at the injection site, skin reactions, phlebitis (inflammation of the vein) or swelling 

• blood clots. 

• acute myeloid leukemia and myelodysplastic syndrome (types of blood cancer) may occur in 
patients who are treated with docetaxel together with certain other anticancer treatments. 

 

Rare (may affect up to 1 in 1,000 people): 

• inflammation of the colon, small intestine, which could be fatal (frequency not known); intestinal 
perforation. 

 

Frequency not known (cannot be estimated from the available data): 

• interstitial lung disease (inflammation of the lungs causing coughing and difficulty breathing. 
Inflammation of the lungs can also develop when docetaxel therapy is used with radiotherapy) 

• pneumonia (infection of the lungs) 

• pulmonary fibrosis (scarring and thickening in the lungs with shortness of breath). 

• blurred vision due to swelling of the retina within the eye (cystoid macular oedema) 

• decrease of the sodium and/or magnesium in your blood (electrolyte balance disorders). 

• ventricular arrhythmia or ventricular tachycardia (manifested as irregular and/or rapid heartbeat, 
severe shortness of breath, dizziness, and/or fainting). Some of these symptoms can be serious. If 

this happens, you must tell your doctor immediately  

• injection site reactions at the site of a previous reaction. 

• non-Hodgkin lymphoma (a cancer affecting the immune system) and other cancers may occur in 
patients who are treated with docetaxel together with certain other anticancer treatments. 

• Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) (blistering, 
peeling or bleeding on any part of your skin (including your lips, eyes, mouth, nose, 

genitals, hands or feet) with or without a rash. You may also have flu-like symptoms at the 

same time, such as fever, chills or aching muscles.) 

• Acute Generalized Exanthematous Pustulosis (AGEP) (red, scaly widespread rash with 
bumps under the swollen skin (including your skin folds, trunk, and upper extremities) and 

blisters accompanied by fever.) 
 



252 

Reporting of side effects 

If you get any side effects, talk to your doctor, hospital pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. You can also report side effects directly via the national reporting 

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 
 

5. How to store DOCETAXEL KABI  
 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the outer carton and on the label of 

the vial after Exp. The expiry date refers to the last day of that month. 

 

Do not store above 25°C. 

Store in the original package in order to protect from light. 

 

Use the vial immediately after its opening. If not used immediately, in-use storage times and 

conditions are the responsibility of the user.  

 

From a microbiological point of view, reconstitution/dilution must take place in controlled and aseptic 

conditions. 

 

Use immediately the medicine once added into the infusion bag. If not used immediately, in-use 

storage times and conditions are the responsibility of the user and would normally not be longer than 6 

hours below 25°C including the one hour infusion. 

 

Docetaxel infusion solution is supersaturated, therefore may cristallize over time. If crystals appear, 

the solution must no longer be used and shall be discarded. 

 

Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines 

you no longer use. These measures will help protect the environment 

 

 

6. Contents of the pack and other information 
 

What DOCETAXEL KABI contains 

- The active substance is docetaxel anhydrous. Each ml of concentrate for solution for infusion 
contains 20 mg docetaxel. 

- The other ingredients are polysorbate 80, ethanol anhydrous (see section 2) and anhydrous citric 
acid (for pH adjustment). 

 

What DOCETAXEL KABI looks like and contents of the pack 

DOCETAXEL KABI concentrate for solution for infusion is a clear, colourless to pale yellow 

solution. 

 

6 ml clear, colourless Type-I glass vial, closed with flurotec rubber stopper and a green flip-off 

aluminium over seal containing 1 ml of concentrate. 

 

Each box contains one vial of 1 ml concentrate (20 mg docetaxel). 

 

Marketing Authorisation Holder  

 

Fresenius Kabi Deutschland GmbH 

Else-Kröner-Straße 1, 

61352 Bad Homburg v.d.Höhe 

Germany 



253 

 
Manufacturer 

Fresenius Kabi Deutschland GmbH 

Pfingstweide 53 

61169 Friedberg 

Germany  

 

Or 
Fresenius Kabi Oncology Plc. 

Lion Court, Farnham Road, Bordon 

Hampshire, GU35 0NF 

United Kingdom 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

This leaflet was last revised in {MM/YYYY} 



254 

The following information is intended for healthcare professionals only: 

 

PREPARATION GUIDE FOR USE WITH DOCETAXEL KABI 20 mg/1 ml CONCENTRATE 

FOR SOLUTION FOR INFUSION  

 

 

It is important that you read the entire contents of this guide prior to the preparation of the 

DOCETAXEL KABI infusion solution. 

 

Recommendations for the safe handling 

Docetaxel is an antineoplastic agent and, as with other potentially toxic compounds, caution should be 

exercised when handling it and preparing its solutions. The use of gloves is recommended. 

 

If DOCETAXEL KABI concentrate or infusion solution should come into contact with skin, wash 

immediately and thoroughly with soap and water. If it should come into contact with mucous 

membranes, wash immediately and thoroughly with water. 

 

Preparation of the intravenous administration 

 

Preparation of the infusion solution 

DO NOT use other docetaxel medicine consisting of 2 vials (concentrate and solvent) with this 

medicine (DOCETAXEL KABI 20 mg/1 ml concentrate for solution for infusion, which contains 

only 1 vial). 

 

DOCETAXEL KABI 20 mg/1 ml concentrate for solution for infusion requires NO prior 

dilution with a solvent and is ready to add to the infusion solution. 

• Each vial is for single use and should be used immediately after opening. If not used immediately, 
in-use storage times and conditions are the responsibility of the user. More than one vial of 

concentrate for solution for infusion may be necessary to obtain the required dose for the patient. 

For example, a dose of 140 mg docetaxel would require 7 ml docetaxel concentrate for solution. 

• Aseptically withdraw the required amount of concentrate for solution for infusion with a calibrated 
syringe. 

In DOCETAXEL KABI 20 mg/1 ml vial the concentration of docetaxel is 20 mg/ml. 

• Then, inject via a single injection (one shot) into a 250 ml infusion bag or bottle containing either 
5% glucose solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. If a dose greater 

than 190 mg of docetaxel is required, use a larger volume of the infusion vehicle so that a 

concentration of 0.74 mg/ml docetaxel is not exceeded. 

• Mix the infusion bag or bottle manually using a rocking motion. 

• From a microbiological point of view, reconstitution /dilution must take place in controlled and 
aseptic conditions and the infusion solution should be used immediately. If not used immediately, 

in-use storage times and conditions are the responsibility of the user. 

Once added as recommended into the infusion bag, the docetaxel infusion solution, if stored below 

25°C, is stable for 6 hours. It should be used within 6 hours (including the one hour infusion 

intravenous administration). 

Docetaxel infusion solution is supersaturated, therefore may crystallize over time. If crystals 

appear, the solution must no longer be used and shall be discarded. 

• As with all parenteral products, infusion solution should be visually inspected prior to use, 
solutions containing a precipitate should be discarded. 

 

Disposal 

All materials that have been utilised for dilution and administration should be disposed of according to 

standard procedures. Do not throw away any medicines via wastewater. Ask your pharmacist how to 

throw away medicines you no longer use. These measures will help protect the environment. 



255 

Package leaflet: Information for the patient 

 

DOCETAXEL KABI 80 mg/4 ml concentrate for solution for infusion 

docetaxel 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor, hospital pharmacist or nurse. 

- If you get any side effects, talk to your doctor, hospital pharmacist or nurse. This includes any 
 possible side effects not listed in this leaflet. See section 4. 

 

What is in this leaflet: 

 

1. What DOCETAXEL KABI is and what it is used for 

2.  What you need to know before you use DOCETAXEL KABI 

3.  How to use DOCETAXEL KABI 

4.  Possible side effects 

5.  How to store DOCETAXEL KABI 

6.  Contents of the pack and other information 

 

 

1. What DOCETAXEL KABI is and what it is used for 
 

The name of this medicine is DOCETAXEL KABI. Its common name is docetaxel. Docetaxel is a 

substance derived from the needles of yew trees. 

Docetaxel belongs to the group of anti-cancer medicines called taxoids. 

 

DOCETAXEL KABI has been prescribed by your doctor for the treatment of breast cancer, special 

forms of lung cancer (non-small cell lung cancer), prostate cancer, gastric cancer or head and neck 

cancer: 

- For the treatment of advanced breast cancer, DOCETAXEL KABI could be administered either 
alone or in combination with doxorubicin, or trastuzumab, or capecitabine. 

- For the treatment of early breast cancer with or without lymph node involvement, DOCETAXEL 
KABI could be administered in combination with doxorubicin and cyclophosphamide. 

- For the treatment of lung cancer, DOCETAXEL KABI could be administered either alone or in 
combination with cisplatin. 

- For the treatment of prostate cancer, DOCETAXEL KABI is administered in combination with 
prednisone or prednisolone. 

- For the treatment of metastatic gastric cancer, DOCETAXEL KABI is administered in 
combination with cisplatin and 5-fluorouracil. 

- For the treatment of head and neck cancer, DOCETAXEL KABI is administered in combination 
with cisplatin and 5-fluorouracil. 

 

 

2. What you need to know before you use DOCETAXEL KABI  
 

You must not be given DOCETAXEL KABI: 

 

• if you are allergic (hypersensitive) to docetaxel or any of the other ingredients of DOCETAXEL 
KABI (listed in section 6). 

• if the number of white blood cells is too low. 

• if you have a severe liver disease. 



256 

Warnings and precautions 

 

Before each treatment with DOCETAXEL KABI, you will have blood tests to check that you have 

enough blood cells and sufficient liver function to receive DOCETAXEL KABI. In case of white 

blood cells disturbances, you may experience associated fever or infections. 

 

Tell your doctor, hospital pharmacist, or nurse immediately if you have abdominal pain or tenderness, 

diarrhoea, rectal haemorrhage, blood in stool or fever. These symptoms may be the first signs of a 

serious gastrointestinal toxicity, which could be fatal. Your doctor should address them immediately. 

 

Tell your doctor, hospital pharmacist or nurse if you have vision problems. In case of vision problems, 

in particular blurred vision, you should immediately have your eyes and vision examined. 

 

Tell your doctor, hospital pharmacist or nurse if you have experienced an allergic reaction to previous 

paclitaxel therapy. 

 

Tell your doctor, hospital pharmacist or nurse if you have heart problems.  

 

If you develop acute or worsening problems with your lungs (fever, shortness of breath or cough), 

please tell your doctor, hospital pharmacist or nurse immediately. Your doctor may stop your 

treatment immediately. 

 

You will be asked to take premedication consisting of an oral corticosteroid such as dexamethasone, 

one day prior to DOCETAXEL KABI administration and to continue for one or two days after it in 

order to minimise certain undesirable effects which may occur after the infusion of DOCETAXEL 

KABI in particular allergic reactions and fluid retention (swelling of the hands, feet, legs or weight 

gain). 

 

During treatment, you may be given other medicines to maintain the number of your blood cells. 

 

Severe skin problems such as Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), 

Acute Generalized Exanthematous Pustulosis (AGEP) have been reported with DOCETAXEL KABI:  

- SJS/TEN symptoms may include blistering, peeling or bleeding on any part of your skin 
(including your lips, eyes, mouth, nose, genitals, hands or feet) with or without a rash. You 

may also have flu-like symptoms at the same time, such as fever, chills or aching muscles. 

- AGEP symptoms may include a red, scaly widespread rash with bumps under the swollen skin 
(including your skin folds, trunk, and upper extremities) and blisters accompanied by fever.  

If you develop severe skin reactions or any of the reactions listed above, immediately contact your 

doctor or healthcare professional. 

 

DOCETAXEL KABI contains alcohol. Discuss with your doctor if you suffer from alcohol 

dependency, epilepsy or liver impairment. See also section “DOCETAXEL KABI contains ethanol 

(alcohol)” below.  

 

Other medicines and DOCETAXEL KABI 
 

Please tell your doctor or hospital pharmacist if you are taking or have recently taken any other 

medicine, including medicines obtained without a prescription. This is because DOCETAXEL KABI 

or the other medicine may not work as well as expected and you may be more likely to get a side 

effect. The amount of alcohol in this medicinal product may alter the effects of other medicines. 

 

Pregnancy, breast-feeding and fertility 

 

Ask your doctor for advice before being given any medicine. 

 

DOCETAXEL KABI must NOT be administered if you are pregnant unless clearly indicated by your 

doctor. 



257 

 

You must not become pregnant during treatment with this medicine and must use an effective method 

of contraception during therapy, because DOCETAXEL KABI may be harmful for the unborn baby. If 

pregnancy occurs during your treatment, you must immediately inform your doctor. 

 

You must not breast-feed while you are treated with DOCETAXEL KABI. 

 

If you are a man being treated with DOCETAXEL KABI you are advised not to father a child during 

and up to 6 months after treatment and to seek advice on conservation of sperm prior to treatment 

because docetaxel may alter male fertility. 

 

Driving and using machines 

 

The amount of alcohol in this medicinal product may impair your ability to drive or use machines. 

You may experience side effects of this medicine that may impair your ability to drive, use tools or 

operate machines (see section 4 Possible side effects). If this happens, do not drive or use any tools or 

machines before discussing with your doctor, nurse or hospital pharmacist. 

 

DOCETAXEL KABI contains ethanol (alcohol). 

 

This medicine contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 1.58 g ethanol anhydrous per 

vial, equivalent to 40 ml of beer or 17 ml wine. 

Harmful for those suffering from alcoholism. 

To be taken into account in pregnant or breast-feeding women, in children and high-risk groups such 

as patients with liver disease, or epilepsy. 

 

The amount of alcohol in this medicine may have effects on the central nervous system (the part of the 

nervous system that includes the brain and spinal cord). 

 

 

3. How to use DOCETAXEL KABI  
 

DOCETAXEL KABI will be administered to you by a healthcare professional. 

 

Usual dose 

 

The dose will depend on your weight and your general condition. Your doctor will calculate your body 

surface area in square meters (m²) and will determine the dose you should receive. 

 

Method and route of administration 

 

DOCETAXEL KABI will be given by infusion into one of your veins (intravenous use). The infusion 

will last approximately one hour during which you will be in the hospital. 

 

Frequency of administration 

 

You should usually receive your infusion once every 3 weeks. 

 

Your doctor may change the dose and frequency of dosing depending on your blood tests, your general 

condition and your response to DOCETAXEL KABI. In particular, please inform your doctor in case 

of diarrhoea, sores in the mouth, feeling of numbness or pins and needles, fever and give her/him 

results of your blood tests. Such information will allow her/him to decide whether a dose reduction is 

needed. If you have any further questions on the use of this medicine, ask your doctor, or hospital 

pharmacist. 

 

 

 



258 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Your doctor will discuss these with you and will explain the potential risks and benefits of your 

treatment. 

 

The most commonly reported adverse reactions of DOCETAXEL KABI alone are: decrease in the 

number of red blood cells or white blood cells, alopecia, nausea, vomiting, sores in the mouth, 

diarrhoea and tiredness. 

 

The severity of adverse events of DOCETAXEL KABI may be increased when DOCETAXEL KABI 

is given in combination with other chemotherapeutic agents. 

 

During the infusion at the hospital the following allergic reactions may occur (may affect more than 1 
in 10 people): 

• flushing, skin reactions, itching 

• chest tightness; difficulty in breathing 

• fever or chills 

• back pain 

• low blood pressure. 
More severe reactions may occur. 

If you had an allergic reaction to paclitaxel, you may also experience an allergic reaction to docetaxel, 

which may be more severe. 

 

The hospital staff will monitor your condition closely during treatment. Tell them immediately if you 

notice any of these effects. 

 

Between infusions of DOCETAXEL KABI the following may occur, and the frequency may vary with 

the combinations of medicines that are received 

 

Very common (may affect more than 1 in 10 people): 

• infections, decrease in the number of red (anaemia), or white blood cells (which are important in 
fighting infection) and platelets 

• fever: if this happens you must tell your doctor immediately 

• allergic reactions as described above 

• loss of appetite (anorexia) 

• insomnia 

• feeling of numbness or pins and needles or pain in the joints or muscles 

• headache 

• alteration in sense of taste 

• inflammation of the eye or increased tearing of the eyes 

• swelling caused by faulty lymphatic drainage 

• shortness of breath 

• nasal drainage; inflammation of the throat and nose; cough 

• bleeding from the nose 

• sores in the mouth 

• stomach upsets including nausea, vomiting and diarrhoea, constipation 

• abdominal pain 

• indigestion 

• hair loss: in most cases normal hair growth should return. In some cases (frequency not known) 
permanent hair loss has been observed 

• redness and swelling of the palms of your hands or soles of your feet which may cause your skin to 
peel (this may also occur on the arms, face, or body) 

• change in the colour of your nails, which may detach 



259 

• muscle aches and pains; back pain or bone pain 

• change or absence of menstrual period 

• swelling of the hands, feet, legs 

• tiredness; or flu-like symptoms 

• weight gain or loss. 

• infection of the upper respiratory tract. 
 

Common (may affect up to 1 in 10 people): 

• oral candidiasis 

• dehydration 

• dizziness 

• hearing impaired 

• decrease in blood pressure; irregular or rapid heart beat 

• heart failure 

• oesophagitis 

• dry mouth 

• difficulty or painful swallowing 

• haemorrhage 

• raised liver enzymes (hence the need for regular blood tests). 

• rises in blood sugar levels (diabetes) 

• decrease of the potassium, calcium and/or phosphate in your blood.  
 

Uncommon (may affect up to 1 in 100 people): 

• fainting 

• at the injection site, skin reactions, phlebitis (inflammation of the vein) or swelling 

• blood clots. 

• acute myeloid leukemia and myelodysplastic syndrome (types of blood cancer) may occur in 
patients who are treated with docetaxel together with certain other anticancer treatments. 

 

Rare (may affect up to 1 in 1,000 people): 

• inflammation of the colon, small intestine, which could be fatal (frequency not known); intestinal 
perforation. 

 

Frequency not known (cannot be estimated from the available data): 

• interstitial lung disease (inflammation of the lungs causing coughing and difficulty breathing. 
Inflammation of the lungs can also develop when docetaxel therapy is used with radiotherapy) 

• pneumonia (infection of the lungs) 

• pulmonary fibrosis (scarring and thickening in the lungs with shortness of breath). 

• blurred vision due to swelling of the retina within the eye (cystoid macular oedema) 

• decrease of the sodium and/or magnesium in your blood (electrolyte balance disorders). 
• ventricular arrhythmia or ventricular tachycardia (manifested as irregular and/or rapid heartbeat, 

severe shortness of breath, dizziness, and/or fainting). Some of these symptoms can be serious. If 

this happens, you must tell your doctor immediately 

• injection site reactions at the site of a previous reaction. 

• non-Hodgkin lymphoma (a cancer affecting the immune system) and other cancers may occur in 
patients who are treated with docetaxel together with certain other anticancer treatments. 

• Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) (blistering, 
peeling or bleeding on any part of your skin (including your lips, eyes, mouth, nose, 

genitals, hands or feet) with or without a rash. You may also have flu-like symptoms at the 

same time, such as fever, chills or aching muscles.) 

• Acute Generalized Exanthematous Pustulosis (AGEP) (red, scaly widespread rash with 
bumps under the swollen skin (including your skin folds, trunk, and upper extremities) and 

blisters accompanied by fever.) 
 



260 

Reporting of side effects 

If you get any side effects, talk to your doctor, hospital pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. You can also report side effects directly via the national reporting 

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 
 

5. How to store DOCETAXEL KABI  
 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the outer carton and on the label of 

the vial after Exp. The expiry date refers to the last day of that month. 

 

Do not store above 25°C. 

Store in the original package in order to protect from light. 

 

Use the vial immediately after its opening. If not used immediately, in-use storage times and 

conditions are the responsibility of the user.  

 

From a microbiological point of view, reconstitution/dilution must take place in controlled and aseptic 

conditions. 

 

Use immediately the medicine once added into the infusion bag. If not used immediately, in-use 

storage times and conditions are the responsibility of the user and would normally not be longer than 6 

hours below 25°C including the one hour infusion. 

 

Docetaxel infusion solution is supersaturated, therefore may cristallize over time. If crystals appear, 

the solution must no longer be used and shall be discarded. 

 

Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines 

you no longer use. These measures will help protect the environment 

 

 

6. Contents of the pack and other information 
 

What DOCETAXEL KABI contains 

- The active substance is docetaxel anhydrous. Each ml of concentrate for solution for infusion 
contains 20 mg docetaxel. 

- The other ingredients are polysorbate 80, ethanol anhydrous (see section 2) and anhydrous citric 
acid (for pH adjustment). 

 

What DOCETAXEL KABI looks like and contents of the pack 

DOCETAXEL KABI concentrate for solution for infusion is a clear, colourless to pale yellow 

solution. 

 

6 ml clear, colourless Type-I glass vial, closed with flurotec rubber stopper and a blue flip-off 

aluminium over seal containing 4 ml of concentrate. 

 

Each box contains one vial of 4 ml concentrate (80 mg docetaxel). 

 

Marketing Authorisation Holder  

Fresenius Kabi Deutschland GmbH 

Else-Kröner-Straße 1, 

61352 Bad Homburg v.d.Höhe 

Germany 

 



261 

Manufacturer 

Fresenius Kabi Deutschland GmbH 

Pfingstweide 53 

61169 Friedberg 

Germany  

 

Or 
Fresenius Kabi Oncology Plc. 

Lion Court, Farnham Road, Bordon 

Hampshire, GU35 0NF 

United Kingdom 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

This leaflet was last revised in {MM/YYYY} 



262 

The following information is intended for healthcare professionals only: 

 

PREPARATION GUIDE FOR USE WITH DOCETAXEL KABI 80 mg/4 ml CONCENTRATE 

FOR SOLUTION FOR INFUSION  

 

 

It is important that you read the entire contents of this guide prior to the preparation of the 

DOCETAXEL KABI infusion solution. 

 

Recommendations for the safe handling 

Docetaxel is an antineoplastic agent and, as with other potentially toxic compounds, caution should be 

exercised when handling it and preparing its solutions. The use of gloves is recommended. 

 

If DOCETAXEL KABI concentrate or infusion solution should come into contact with skin, wash 

immediately and thoroughly with soap and water. If it should come into contact with mucous 

membranes, wash immediately and thoroughly with water. 

 

Preparation of the intravenous administration 

 

Preparation of the infusion solution 

DO NOT use other docetaxel medicine consisting of 2 vials (concentrate and solvent) with this 

medicine (DOCETAXEL KABI 80 mg/4 ml concentrate for solution for infusion, which contains 

only 1 vial). 

 

DOCETAXEL KABI 80 mg/4 ml concentrate for solution for infusion requires NO prior 

dilution with a solvent and is ready to add to the infusion solution. 

• Each vial is for single use and should be used immediately after opening. If not used immediately, 
in-use storage times and conditions are the responsibility of the user. More than one vial of 

concentrate for solution for infusion may be necessary to obtain the required dose for the patient. 

For example, a dose of 140 mg docetaxel would require 7 ml docetaxel concentrate for solution. 

• Aseptically withdraw the required amount of concentrate for solution for infusion with a calibrated 
syringe. 

In DOCETAXEL KABI 80 mg/4 ml vial the concentration of docetaxel is 20 mg/ml. 

• Then, inject via a single injection (one shot) into a 250 ml infusion bag or bottle containing either 
5% glucose solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. If a dose greater 

than 190 mg of docetaxel is required, use a larger volume of the infusion vehicle so that a 

concentration of 0.74 mg/ml docetaxel is not exceeded. 

• Mix the infusion bag or bottle manually using a rocking motion. 

• From a microbiological point of view, reconstitution /dilution must take place in controlled and 
aseptic conditions and the infusion solution should be used immediately. If not used immediately, 

in-use storage times and conditions are the responsibility of the user. 

Once added as recommended into the infusion bag, the docetaxel infusion solution, if stored below 

25°C, is stable for 6 hours. It should be used within 6 hours (including the one hour infusion 

intravenous administration). 

Docetaxel infusion solution is supersaturated, therefore may crystallize over time. If crystals 

appear, the solution must no longer be used and shall be discarded. 

• As with all parenteral products, infusion solution should be visually inspected prior to use, 
solutions containing a precipitate should be discarded. 

 

Disposal 

All materials that have been utilised for dilution and administration should be disposed of according to 

standard procedures. Do not throw away any medicines via wastewater. Ask your pharmacist how to 

throw away medicines you no longer use. These measures will help protect the environment. 



263 

Package leaflet: Information for the patient 

 

DOCETAXEL KABI 120 mg/6 ml concentrate for solution for infusion 

docetaxel 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor, hospital pharmacist or nurse. 

- If you get any side effects, talk to your doctor, hospital pharmacist or nurse. This includes any 
 possible side effects not listed in this leaflet. See section 4. 

 

What is in this leaflet: 

 

1. What DOCETAXEL KABI is and what it is used for 

2.  What you need to know before you use DOCETAXEL KABI 

3.  How to use DOCETAXEL KABI 

4.  Possible side effects 

5.  How to store DOCETAXEL KABI 

6.  Contents of the pack and other information 

 

 

1. What DOCETAXEL KABI is and what it is used for 
 

The name of this medicine is DOCETAXEL KABI. Its common name is docetaxel. Docetaxel is a 

substance derived from the needles of yew trees. 

Docetaxel belongs to the group of anti-cancer medicines called taxoids. 

 

DOCETAXEL KABI has been prescribed by your doctor for the treatment of breast cancer, special 

forms of lung cancer (non-small cell lung cancer), prostate cancer, gastric cancer or head and neck 

cancer: 

- For the treatment of advanced breast cancer, DOCETAXEL KABI could be administered either 
alone or in combination with doxorubicin, or trastuzumab, or capecitabine. 

- For the treatment of early breast cancer with or without lymph node involvement, DOCETAXEL 
KABI could be administered in combination with doxorubicin and cyclophosphamide. 

- For the treatment of lung cancer, DOCETAXEL KABI could be administered either alone or in 
combination with cisplatin. 

- For the treatment of prostate cancer, DOCETAXEL KABI is administered in combination with 
prednisone or prednisolone. 

- For the treatment of metastatic gastric cancer, DOCETAXEL KABI is administered in 
combination with cisplatin and 5-fluorouracil. 

- For the treatment of head and neck cancer, DOCETAXEL KABI is administered in combination 
with cisplatin and 5-fluorouracil. 

 

 

2. What you need to know before you use DOCETAXEL KABI  
 

You must not be given DOCETAXEL KABI 

 

• if you are allergic (hypersensitive) to docetaxel or any of the other ingredients of DOCETAXEL 
KABI (listed in section 6). 

• if the number of white blood cells is too low. 

• if you have a severe liver disease. 



264 

Warnings and precautions 

 

Before each treatment with DOCETAXEL KABI, you will have blood tests to check that you have 

enough blood cells and sufficient liver function to receive DOCETAXEL KABI. In case of white 

blood cells disturbances, you may experience associated fever or infections. 

 

Tell your doctor, hospital pharmacist, or nurse immediately if you have abdominal pain or tenderness, 

diarrhoea, rectal haemorrhage, blood in stool or fever. These symptoms may be the first signs of a 

serious gastrointestinal toxicity, which could be fatal. Your doctor should address them immediately. 

 

Tell your doctor, hospital pharmacist or nurse if you have vision problems. In case of vision 

problems, in particular blurred vision, you should immediately have your eyes and vision examined.  

 

Tell your doctor, hospital pharmacist or nurse if you have experienced an allergic reaction to previous 

paclitaxel therapy. 

 

Tell your doctor, hospital pharmacist or nurse if you have heart problems. 

 

If you develop acute or worsening problems with your lungs (fever, shortness of breath or cough), 

please tell your doctor, hospital pharmacist or nurse immediately. Your doctor may stop your 

treatment immediately. 

 

You will be asked to take premedication consisting of an oral corticosteroid such as dexamethasone, 

one day prior to DOCETAXEL KABI administration and to continue for one or two days after it in 

order to minimise certain undesirable effects which may occur after the infusion of DOCETAXEL 

KABI in particular allergic reactions and fluid retention (swelling of the hands, feet, legs or weight 

gain). 

 

During treatment, you may be given other medicines to maintain the number of your blood cells. 

 

Severe skin problems such as Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), 

Acute Generalized Exanthematous Pustulosis (AGEP) have been reported with DOCETAXEL KABI:  

- SJS/TEN symptoms may include blistering, peeling or bleeding on any part of your skin 
(including your lips, eyes, mouth, nose, genitals, hands or feet) with or without a rash. You 

may also have flu-like symptoms at the same time, such as fever, chills or aching muscles. 

- AGEP symptoms may include a red, scaly widespread rash with bumps under the swollen skin 
(including your skin folds, trunk, and upper extremities) and blisters accompanied by fever.  

If you develop severe skin reactions or any of the reactions listed above, immediately contact your 

doctor or healthcare professional. 

 

DOCETAXEL KABI contains alcohol. Discuss with your doctor if you suffer from alcohol 

dependency epilepsy or liver impairment. See also section “DOCETAXEL KABI contains ethanol 

(alcohol)” below.  

 

Other medicines and DOCETAXEL KABI 
 

Please tell your doctor or hospital pharmacist if you are taking or have recently taken any other 

medicine, including medicines obtained without a prescription. This is because DOCETAXEL KABI 

or the other medicine may not work as well as expected and you may be more likely to get a side 

effect. The amount of alcohol in this medicinal product may alter the effects of other 

medicines. 
 

Pregnancy, breast-feeding and fertility 

 

Ask your doctor for advice before being given any medicine. 

 



265 

DOCETAXEL KABI must NOT be administered if you are pregnant unless clearly indicated by your 

doctor. 

 

You must not become pregnant during treatment with this medicine and must use an effective method 

of contraception during therapy, because DOCETAXEL KABI may be harmful for the unborn baby. If 

pregnancy occurs during your treatment, you must immediately inform your doctor. 

 

You must not breast-feed while you are treated with DOCETAXEL KABI. 

 

If you are a man being treated with DOCETAXEL KABI you are advised not to father a child during 

and up to 6 months after treatment and to seek advice on conservation of sperm prior to treatment 

because docetaxel may alter male fertility. 

 

Driving and using machines 

 

The amount of alcohol in this medicinal product may impair your ability to drive or use machines. 

You may experience side effects of this medicine that may impair your ability to drive, use tools or 

operate machines (see section 4 Possible side effects). If this happens, do not drive or use any tools or 

machines before discussing with your doctor, nurse or hospital pharmacist. 

 

DOCETAXEL KABI contains ethanol (alcohol). 

 

This medicine contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 2.37 g ethanol anhydrous per 

vial, equivalent to 60 ml of beer or 24 ml wine. 

Harmful for those suffering from alcoholism. 

To be taken into account in pregnant or breast-feeding women, in children and high-risk groups such 

as patients with liver disease, or epilepsy. 

 

The amount of alcohol in this medicine may have effects on the central nervous system (the part of the 

nervous system that includes the brain and spinal cord). 

 

 

3. How to use DOCETAXEL KABI  
 

DOCETAXEL KABI will be administered to you by a healthcare professional. 

 

Usual dose 

 

The dose will depend on your weight and your general condition. Your doctor will calculate your body 

surface area in square meters (m²) and will determine the dose you should receive. 

 

Method and route of administration 

 

DOCETAXEL KABI will be given by infusion into one of your veins (intravenous use). The infusion 

will last approximately one hour during which you will be in the hospital. 

 

Frequency of administration 

 

You should usually receive your infusion once every 3 weeks. 

 

Your doctor may change the dose and frequency of dosing depending on your blood tests, your general 

condition and your response to DOCETAXEL KABI. In particular, please inform your doctor in case 

of diarrhoea, sores in the mouth, feeling of numbness or pins and needles, fever and give her/him 

results of your blood tests. Such information will allow her/him to decide whether a dose reduction is 

needed. If you have any further questions on the use of this medicine, ask your doctor, or hospital 

pharmacist. 

 



266 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Your doctor will discuss these with you and will explain the potential risks and benefits of your 

treatment. 

 

The most commonly reported adverse reactions of DOCETAXEL KABI alone are: decrease in the 

number of red blood cells or white blood cells, alopecia, nausea, vomiting, sores in the mouth, 

diarrhoea and tiredness. 

 

The severity of adverse events of DOCETAXEL KABI may be increased when DOCETAXEL KABI 

is given in combination with other chemotherapeutic agents. 

 

During the infusion at the hospital the following allergic reactions may occur (may affect more than 1 
in 10 people): 

• flushing, skin reactions, itching 

• chest tightness; difficulty in breathing 

• fever or chills 

• back pain 

• low blood pressure. 
More severe reactions may occur. 

If you had an allergic reaction to paclitaxel, you may also experience an allergic reaction to docetaxel, 

which may be more severe. 

 

The hospital staff will monitor your condition closely during treatment. Tell them immediately if you 

notice any of these effects. 

 

Between infusions of DOCETAXEL KABI the following may occur, and the frequency may vary with 

the combinations of medicines that are received 

 

Very common (may affect more than 1 in 10 people): 

• infections, decrease in the number of red (anaemia), or white blood cells (which are important in 
fighting infection) and platelets 

• fever: if this happens you must tell your doctor immediately 

• allergic reactions as described above 

• loss of appetite (anorexia) 

• insomnia 

• feeling of numbness or pins and needles or pain in the joints or muscles 

• headache 

• alteration in sense of taste 

• inflammation of the eye or increased tearing of the eyes 

• swelling caused by faulty lymphatic drainage 

• shortness of breath 

• nasal drainage; inflammation of the throat and nose; cough 

• bleeding from the nose 

• sores in the mouth 

• stomach upsets including nausea, vomiting and diarrhoea, constipation 

• abdominal pain 

• indigestion 

• hair loss: in most cases normal hair growth should return. In some cases (frequency not known) 
permanent hair loss has been observed 

• redness and swelling of the palms of your hands or soles of your feet which may cause your skin to 
peel (this may also occur on the arms, face, or body) 

• change in the colour of your nails, which may detach 



267 

• muscle aches and pains; back pain or bone pain 

• change or absence of menstrual period 

• swelling of the hands, feet, legs 

• tiredness; or flu-like symptoms 

• weight gain or loss. 

• infection of the upper respiratory tract. 
 

Common (may affect up to 1 in 10 people): 

• oral candidiasis 

• dehydration 

• dizziness 

• hearing impaired 

• decrease in blood pressure; irregular or rapid heart beat 

• heart failure 

• oesophagitis 

• dry mouth 

• difficulty or painful swallowing 

• haemorrhage 

• raised liver enzymes (hence the need for regular blood tests). 

• rises in blood sugar levels (diabetes) 

• decrease of the potassium, calcium and/or phosphate in your blood.  
 

Uncommon (may affect up to 1 in 100 people): 

• fainting 

• at the injection site, skin reactions, phlebitis (inflammation of the vein) or swelling 

• blood clots. 

• acute myeloid leukemia and myelodysplastic syndrome (types of blood cancer) may occur in 
patients who are treated with docetaxel together with certain other anticancer treatments. 

 

Rare (may affect up to 1 in 1,000 people): 

• inflammation of the colon, small intestine, which could be fatal (frequency not known); intestinal 
perforation. 

 

Frequency not known (cannot be estimated from the available data): 

• interstitial lung disease (inflammation of the lungs causing coughing and difficulty breathing. 
Inflammation of the lungs can also develop when docetaxel therapy is used with radiotherapy) 

• pneumonia (infection of the lungs) 

• pulmonary fibrosis (scarring and thickening in the lungs with shortness of breath). 

• blurred vision due to swelling of the retina within the eye (cystoid macular oedema) 

• decrease of the sodium and/or magnesium in your blood (electrolyte balance disorders). 
• ventricular arrhythmia or ventricular tachycardia (manifested as irregular and/or rapid heartbeat, 

severe shortness of breath, dizziness, and/or fainting). Some of these symptoms can be serious. If 

this happens, you must tell your doctor immediately 

• injection site reactions at the site of a previous reaction. 

• non-Hodgkin lymphoma (a cancer affecting the immune system) and other cancers may occur in 
patients who are treated with docetaxel together with certain other anticancer treatments. 

• Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) (blistering, 
peeling or bleeding on any part of your skin (including your lips, eyes, mouth, nose, 

genitals, hands or feet) with or without a rash. You may also have flu-like symptoms at the 

same time, such as fever, chills or aching muscles.) 

• Acute Generalized Exanthematous Pustulosis (AGEP) (red, scaly widespread rash with 
bumps under the swollen skin (including your skin folds, trunk, and upper extremities) and 

blisters accompanied by fever.) 
 



268 

Reporting of adverse effects 

If you get any side effects, talk to your doctor, hospital pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. You can also report side effects directly via the national reporting 

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 

 

5. How to store DOCETAXEL KABI  
 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the outer carton and on the label of 

the vial after Exp. The expiry date refers to the last day of that month. 

 

Do not store above 25°C. 

Store in the original package in order to protect from light. 

 

Use the vial immediately after its opening. If not used immediately, in-use storage times and 

conditions are the responsibility of the user.  

 

From a microbiological point of view, reconstitution/dilution must take place in controlled and aseptic 

conditions. 

 

Use immediately the medicine once added into the infusion bag. If not used immediately, in-use 

storage times and conditions are the responsibility of the user and would normally not be longer than 6 

hours below 25°C including the one hour infusion. 

 

Docetaxel infusion solution is supersaturated, therefore may cristallize over time. If crystals appear, 

the solution must no longer be used and shall be discarded. 

 

Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines 

you no longer use. These measures will help protect the environment 

 

 

6. Contents of the pack and other information 
 

What DOCETAXEL KABI contains 

- The active substance is docetaxel anhydrous. Each ml of concentrate for solution for infusion 
contains 20 mg docetaxel. 

- The other ingredients are polysorbate 80, ethanol anhydrous (see section 2) and anhydrous citric 
acid (for pH adjustment). 

 

What DOCETAXEL KABI looks like and contents of the pack 

DOCETAXEL KABI concentrate for solution for infusion is a clear, colourless to pale yellow 

solution. 

 

6 ml clear, colourless Type-I glass vial, closed with flurotec rubber stopper and a red flip-off 

aluminium over seal containing 6 ml of concentrate. 

 

Each box contains one vial of 6 ml concentrate (120 mg docetaxel). 

 

Marketing Authorisation Holder  

Fresenius Kabi Deutschland GmbH 

Else-Kröner-Straße 1, 

61352 Bad Homburg v.d.Höhe 

Germany 

 



269 

Manufacturer 

Fresenius Kabi Deutschland GmbH 

Pfingstweide 53 

61169 Friedberg 

Germany  

 

Or 
Fresenius Kabi Oncology Plc. 

Lion Court, Farnham Road, Bordon 

Hampshire, GU35 0NF 

United Kingdom 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

This leaflet was last revised in {MM/YYYY} 



270 

The following information is intended for healthcare professionals only: 

 

PREPARATION GUIDE FOR USE WITH DOCETAXEL KABI 120 mg/6 ml 

CONCENTRATE FOR SOLUTION FOR INFUSION  

 

 

It is important that you read the entire contents of this guide prior to the preparation of the 

DOCETAXEL KABI infusion solution. 

 

Recommendations for the safe handling 

Docetaxel is an antineoplastic agent and, as with other potentially toxic compounds, caution should be 

exercised when handling it and preparing its solutions. The use of gloves is recommended. 

 

If DOCETAXEL KABI concentrate or infusion solution should come into contact with skin, wash 

immediately and thoroughly with soap and water. If it should come into contact with mucous 

membranes, wash immediately and thoroughly with water. 

 

Preparation of the intravenous administration 

 

Preparation of the infusion solution 

DO NOT use other docetaxel medicine consisting of 2 vials (concentrate and solvent) with this 

medicine (DOCETAXEL KABI 120 mg/6 ml concentrate for solution for infusion, which 

contains only 1 vial). 

 

DOCETAXEL KABI 120 mg/6 ml concentrate for solution for infusion requires NO prior 

dilution with a solvent and is ready to add to the infusion solution. 

• Each vial is for single use and should be used immediately after opening. If not used immediately, 
in-use storage times and conditions are the responsibility of the user. More than one vial of 

concentrate for solution for infusion may be necessary to obtain the required dose for the patient. 

For example, a dose of 140 mg docetaxel would require 7 ml docetaxel concentrate for solution. 

• Aseptically withdraw the required amount of concentrate for solution for infusion with a calibrated 
syringe. 

In DOCETAXEL KABI 120 mg/6 ml vial the concentration of docetaxel is 20 mg/ml. 

• Then, inject via a single injection (one shot) into a 250 ml infusion bag or bottle containing either 
5% glucose solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. If a dose greater 

than 190 mg of docetaxel is required, use a larger volume of the infusion vehicle so that a 

concentration of 0.74 mg/ml docetaxel is not exceeded. 

• Mix the infusion bag or bottle manually using a rocking motion. 

• From a microbiological point of view, reconstitution /dilution must take place in controlled and 
aseptic conditions and the infusion solution should be used immediately. If not used immediately, 

in-use storage times and conditions are the responsibility of the user. 

Once added as recommended into the infusion bag, the docetaxel infusion solution, if stored below 

25°C, is stable for 6 hours. It should be used within 6 hours (including the one hour infusion 

intravenous administration). 

Docetaxel infusion solution is supersaturated, therefore may crystallize over time. If crystals 

appear, the solution must no longer be used and shall be discarded. 

• As with all parenteral products, infusion solution should be visually inspected prior to use, 
solutions containing a precipitate should be discarded. 

 

Disposal 

All materials that have been utilised for dilution and administration should be disposed of according to 

standard procedures. Do not throw away any medicines via wastewater. Ask your pharmacist how to 

throw away medicines you no longer use. These measures will help protect the environment. 



271 

Package leaflet: Information for the patient 

 

DOCETAXEL KABI 160 mg/8 ml concentrate for solution for infusion 

docetaxel 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor, hospital pharmacist or nurse. 

- If you get any side effects, talk to your doctor, hospital pharmacist or nurse. This includes any 
 possible side effects not listed in this leaflet. See section 4.  

 

What is in this leaflet: 

 

1. What DOCETAXEL KABI is and what it is used for 

2.  What you need to know before you use DOCETAXEL KABI 

3.  How to use DOCETAXEL KABI 

4.  Possible side effects 

5.  How to store DOCETAXEL KABI 

6.  Contents of the pack and other information 

 

 

1. What DOCETAXEL KABI is and what it is used for 
 

The name of this medicine is DOCETAXEL KABI. Its common name is docetaxel. Docetaxel is a 

substance derived from the needles of yew trees. 

Docetaxel belongs to the group of anti-cancer medicines called taxoids. 

 

DOCETAXEL KABI has been prescribed by your doctor for the treatment of breast cancer, special 

forms of lung cancer (non-small cell lung cancer), prostate cancer, gastric cancer or head and neck 

cancer: 

- For the treatment of advanced breast cancer, DOCETAXEL KABI could be administered either 
alone or in combination with doxorubicin, or trastuzumab, or capecitabine. 

- For the treatment of early breast cancer with or without lymph node involvement, DOCETAXEL 
KABI could be administered in combination with doxorubicin and cyclophosphamide. 

- For the treatment of lung cancer, DOCETAXEL KABI could be administered either alone or in 
combination with cisplatin. 

- For the treatment of prostate cancer, DOCETAXEL KABI is administered in combination with 
prednisone or prednisolone. 

- For the treatment of metastatic gastric cancer, DOCETAXEL KABI is administered in 
combination with cisplatin and 5-fluorouracil. 

- For the treatment of head and neck cancer, DOCETAXEL KABI is administered in combination 
with cisplatin and 5-fluorouracil. 

 

 

2. What you need to know before you use DOCETAXEL KABI  
 

You must not be given DOCETAXEL KABI: 

 

• if you are allergic (hypersensitive) to docetaxel or any of the other ingredients of DOCETAXEL 
KABI (listed in section 6). 

• if the number of white blood cells is too low. 

• if you have a severe liver disease. 



272 

Warnings and precautions 

 

Before each treatment with DOCETAXEL KABI, you will have blood tests to check that you have 

enough blood cells and sufficient liver function to receive DOCETAXEL KABI. In case of white 

blood cells disturbances, you may experience associated fever or infections. 

 

Tell your doctor, hospital pharmacist, or nurse immediately if you have abdominal pain or tenderness, 

diarrhoea, rectal haemorrhage, blood in stool or fever. These symptoms may be the first signs of a 

serious gastrointestinal toxicity, which could be fatal. Your doctor should address them immediately. 

 

Tell your doctor, hospital pharmacist or nurse if you have vision problems. In case of vision 

problems, in particular blurred vision, you should immediately have your eyes and vision examined.  

 

Tell your doctor, hospital pharmacist or nurse if you have experienced an allergic reaction to previous 

paclitaxel therapy. 

 

Tell your doctor, hospital pharmacist or nurse if you have heart problems.  

 

If you develop acute or worsening problems with your lungs (fever, shortness of breath or cough), 

please tell your doctor, hospital pharmacist or nurse immediately. Your doctor may stop your 

treatment immediately. 

 

You will be asked to take premedication consisting of an oral corticosteroid such as dexamethasone, 

one day prior to DOCETAXEL KABI administration and to continue for one or two days after it in 

order to minimise certain undesirable effects which may occur after the infusion of DOCETAXEL 

KABI in particular allergic reactions and fluid retention (swelling of the hands, feet, legs or weight 

gain). 

 

During treatment, you may be given other medicines to maintain the number of your blood cells. 

 

Severe skin problems such as Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), 

Acute Generalized Exanthematous Pustulosis (AGEP) have been reported with DOCETAXEL KABI:  

- SJS/TEN symptoms may include blistering, peeling or bleeding on any part of your skin 
(including your lips, eyes, mouth, nose, genitals, hands or feet) with or without a rash. You 

may also have flu-like symptoms at the same time, such as fever, chills or aching muscles. 

- AGEP symptoms may include a red, scaly widespread rash with bumps under the swollen skin 
(including your skin folds, trunk, and upper extremities) and blisters accompanied by fever.  

If you develop severe skin reactions or any of the reactions listed above, immediately contact your 

doctor or healthcare professional. 

 

DOCETAXEL KABI contains alcohol. Discuss with your doctor if you suffer from alcohol 

dependency, epilepsy or liver impairment. See also section “DOCETAXEL KABI contains ethanol 

(alcohol)” below.  

 

Other medicines and DOCETAXEL KABI 
 

Please tell your doctor or hospital pharmacist if you are taking or have recently taken any other 

medicine, including medicines obtained without a prescription. This is because DOCETAXEL KABI 

or the other medicine may not work as well as expected and you may be more likely to get a side 

effect. The amount of alcohol in this medicinal product may alter the effects of other medicines. 

 

Pregnancy, breast-feeding and fertility 

 

Ask your doctor for advice before being given any medicine. 

 

DOCETAXEL KABI must NOT be administered if you are pregnant unless clearly indicated by your 

doctor. 



273 

 

You must not become pregnant during treatment with this medicine and must use an effective method 

of contraception during therapy, because DOCETAXEL KABI may be harmful for the unborn baby. If 

pregnancy occurs during your treatment, you must immediately inform your doctor. 

 

You must not breast-feed while you are treated with DOCETAXEL KABI. 

 

If you are a man being treated with DOCETAXEL KABI you are advised not to father a child during 

and up to 6 months after treatment and to seek advice on conservation of sperm prior to treatment 

because docetaxel may alter male fertility. 

Driving and using machines 

 

The amount of alcohol in this medicinal product may impair your ability to drive or use machines. 

You may experience side effects of this medicine that may impair your ability to drive, use tools or 

operate machines (see section 4 Possible side effects). If this happens, do not drive or use any tools or 

machines before discussing with your doctor, nurse or hospital pharmacist. 

 

DOCETAXEL KABI contains ethanol (alcohol). 

 

This medicine contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 3.16 g ethanol anhydrous per 

vial, equivalent to 80 ml of beer or 32 ml wine. 

Harmful for those suffering from alcoholism. 

To be taken into account in pregnant or breast-feeding women, in children and high-risk groups such 

as patients with liver disease, or epilepsy. 

 

The amount of alcohol in this medicine may have effects on the central nervous system (the part of the 

nervous system that includes the brain and spinal cord). 

 

 

3. How to use DOCETAXEL KABI  
 

DOCETAXEL KABI will be administered to you by a healthcare professional. 

 

Usual dose 

 

The dose will depend on your weight and your general condition. Your doctor will calculate your body 

surface area in square meters (m²) and will determine the dose you should receive. 

 

Method and route of administration 

 

DOCETAXEL KABI will be given by infusion into one of your veins (intravenous use). The infusion 

will last approximately one hour during which you will be in the hospital. 

 

Frequency of administration 

 

You should usually receive your infusion once every 3 weeks. 

 

Your doctor may change the dose and frequency of dosing depending on your blood tests, your general 

condition and your response to DOCETAXEL KABI. In particular, please inform your doctor in case 

of diarrhoea, sores in the mouth, feeling of numbness or pins and needles, fever and give her/him 

results of your blood tests. Such information will allow her/him to decide whether a dose reduction is 

needed. If you have any further questions on the use of this medicine, ask your doctor, or hospital 

pharmacist. 

 

 

 

 



274 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Your doctor will discuss these with you and will explain the potential risks and benefits of your 

treatment. 

 

The most commonly reported adverse reactions of DOCETAXEL KABI alone are: decrease in the 

number of red blood cells or white blood cells, alopecia, nausea, vomiting, sores in the mouth, 

diarrhoea and tiredness. 

 

The severity of adverse events of DOCETAXEL KABI may be increased when DOCETAXEL KABI 

is given in combination with other chemotherapeutic agents. 

 

During the infusion at the hospital the following allergic reactions may occur (may affect more than 1 
in 10 people): 

• flushing, skin reactions, itching 

• chest tightness; difficulty in breathing 

• fever or chills 

• back pain 

• low blood pressure. 
More severe reactions may occur. 

If you had an allergic reaction to paclitaxel, you may also experience an allergic reaction to docetaxel, 

which may be more severe. 

 

The hospital staff will monitor your condition closely during treatment. Tell them immediately if you 

notice any of these effects. 

 

Between infusions of DOCETAXEL KABI the following may occur, and the frequency may vary with 

the combinations of medicines that are received 

 

Very common (may affect more than 1 in 10 people): 

• infections, decrease in the number of red (anaemia), or white blood cells (which are important in 
fighting infection) and platelets 

• fever: if this happens you must tell your doctor immediately 

• allergic reactions as described above 

• loss of appetite (anorexia) 

• insomnia 

• feeling of numbness or pins and needles or pain in the joints or muscles 

• headache 

• alteration in sense of taste 

• inflammation of the eye or increased tearing of the eyes 

• swelling caused by faulty lymphatic drainage 

• shortness of breath 

• nasal drainage; inflammation of the throat and nose; cough 

• bleeding from the nose 

• sores in the mouth 

• stomach upsets including nausea, vomiting and diarrhoea, constipation 

• abdominal pain 

• indigestion 

• hair loss: in most cases normal hair growth should return. In some cases (frequency not known) 
permanent hair loss has been observed 

• redness and swelling of the palms of your hands or soles of your feet which may cause your skin to 
peel (this may also occur on the arms, face, or body) 

• change in the colour of your nails, which may detach 



275 

• muscle aches and pains; back pain or bone pain 

• change or absence of menstrual period 

• swelling of the hands, feet, legs 

• tiredness; or flu-like symptoms 

• weight gain or loss. 

• infection of the upper respiratory tract. 
 

Common (may affect up to 1 in 10 people): 

• oral candidiasis 

• dehydration 

• dizziness 

• hearing impaired 

• decrease in blood pressure; irregular or rapid heart beat 

• heart failure 

• oesophagitis 

• dry mouth 

• difficulty or painful swallowing 

• haemorrhage 

• raised liver enzymes (hence the need for regular blood tests). 

• rises in blood sugar levels (diabetes) 

• decrease of the potassium, calcium and/or phosphate in your blood.  
 

Uncommon (may affect up to 1 in 100 people): 

• fainting 

• at the injection site, skin reactions, phlebitis (inflammation of the vein) or swelling 

• blood clots. 

• acute myeloid leukemia and myelodysplastic syndrome (types of blood cancer) may occur in 
patients who are treated with docetaxel together with certain other anticancer treatments. 

 

Rare (may affect up to 1 in 1,000 people): 

• inflammation of the colon, small intestine, which could be fatal (frequency not known); intestinal 
perforation. 

 

Frequency not known (cannot be estimated from the available data): 

• interstitial lung disease (inflammation of the lungs causing coughing and difficulty breathing. 
Inflammation of the lungs can also develop when docetaxel therapy is used with radiotherapy) 

• pneumonia (infection of the lungs) 

• pulmonary fibrosis (scarring and thickening in the lungs with shortness of breath). 

• blurred vision due to swelling of the retina within the eye (cystoid macular oedema) 

• decrease of the sodium and/or magnesium in your blood (electrolyte balance disorders). 
• ventricular arrhythmia or ventricular tachycardia (manifested as irregular and/or rapid heartbeat, 

severe shortness of breath, dizziness, and/or fainting). Some of these symptoms can be serious. If 

this happens, you must tell your doctor immediately 

• injection site reactions at the site of a previous reaction. 

• non-Hodgkin lymphoma (a cancer affecting the immune system) and other cancers may occur in 
patients who are treated with docetaxel together with certain other anticancer treatments. 

• Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) (blistering, 
peeling or bleeding on any part of your skin (including your lips, eyes, mouth, nose, 

genitals, hands or feet) with or without a rash. You may also have flu-like symptoms at the 

same time, such as fever, chills or aching muscles.) 

• Acute Generalized Exanthematous Pustulosis (AGEP) (red, scaly widespread rash with 
bumps under the swollen skin (including your skin folds, trunk, and upper extremities) and 

blisters accompanied by fever.) 
 



276 

Reporting of adverse effects 

If you get any side effects, talk to your doctor, hospital pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. You can also report side effects directly via the national reporting 

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 

 

5. How to store DOCETAXEL KABI  
 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the outer carton and on the label of 

the vial after Exp. The expiry date refers to the last day of that month. 

 

Do not store above 25°C. 

Store in the original package in order to protect from light. 

 

Use the vial immediately after its opening. If not used immediately, in-use storage times and 

conditions are the responsibility of the user.  

 

From a microbiological point of view, reconstitution/dilution must take place in controlled and aseptic 

conditions. 

 

Use immediately the medicine once added into the infusion bag. If not used immediately, in-use 

storage times and conditions are the responsibility of the user and would normally not be longer than 6 

hours below 25°C including the one hour infusion. 

 

Docetaxel infusion solution is supersaturated, therefore may cristallize over time. If crystals appear, 

the solution must no longer be used and shall be discarded. 

 

Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines 

you no longer use. These measures will help protect the environment 

 

 

6. Contents of the pack and other information 
 

What DOCETAXEL KABI contains 

- The active substance is docetaxel anhydrous. Each ml of concentrate for solution for infusion 
contains 20 mg docetaxel. 

- The other ingredients are polysorbate 80, ethanol anhydrous (see section 2) and anhydrous citric 
acid (for pH adjustment). 

 

What DOCETAXEL KABI looks like and contents of the pack 

DOCETAXEL KABI concentrate for solution for infusion is a clear, colourless to pale yellow 

solution. 

 

10 ml clear, colourless Type-I glass vial, closed with flurotec rubber stopper and a yellow flip-off 

aluminium over seal containing 8 ml of concentrate. 

 

Each box contains one vial of 8 ml concentrate (160 mg docetaxel). 

 

Marketing Authorisation Holder  

Fresenius Kabi Deutschland GmbH 

Else-Kröner-Straße 1, 

61352 Bad Homburg v.d.Höhe 

Germany 

 



277 

Manufacturer 

Fresenius Kabi Deutschland GmbH 

Pfingstweide 53 

61169 Friedberg 

Germany  

 

Or 

 
Fresenius Kabi Oncology Plc. 

Lion Court, Farnham Road, Bordon 

Hampshire, GU35 0NF 

United Kingdom 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

This leaflet was last revised in {MM/YYYY} 



278 

The following information is intended for healthcare professionals only: 

 

PREPARATION GUIDE FOR USE WITH DOCETAXEL KABI 160 mg/8 ml 

CONCENTRATE FOR SOLUTION FOR INFUSION  

 

 

It is important that you read the entire contents of this guide prior to the preparation of the 

DOCETAXEL KABI infusion solution. 

 

Recommendations for the safe handling 

Docetaxel is an antineoplastic agent and, as with other potentially toxic compounds, caution should be 

exercised when handling it and preparing its solutions. The use of gloves is recommended. 

 

If DOCETAXEL KABI concentrate or infusion solution should come into contact with skin, wash 

immediately and thoroughly with soap and water. If it should come into contact with mucous 

membranes, wash immediately and thoroughly with water. 

 

Preparation of the intravenous administration 

 

Preparation of the infusion solution 

DO NOT use other docetaxel medicine consisting of 2 vials (concentrate and solvent) with this 

medicine (DOCETAXEL KABI 160 mg/8 ml concentrate for solution for infusion, which 

contains only 1 vial). 

 

DOCETAXEL KABI 160 mg/8 ml concentrate for solution for infusion requires NO prior 

dilution with a solvent and is ready to add to the infusion solution. 

• Each vial is for single use and should be used immediately after opening. If not used immediately, 
in-use storage times and conditions are the responsibility of the user. More than one vial of 

concentrate for solution for infusion may be necessary to obtain the required dose for the patient. 

For example, a dose of 140 mg docetaxel would require 7 ml docetaxel concentrate for solution. 

• Aseptically withdraw the required amount of concentrate for solution for infusion with a calibrated 
syringe. 

In DOCETAXEL KABI 160 mg/8 ml vial the concentration of docetaxel is 20 mg/ml. 

• Then, inject via a single injection (one shot) into a 250 ml infusion bag or bottle containing either 
5% glucose solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. If a dose greater 

than 190 mg of docetaxel is required, use a larger volume of the infusion vehicle so that a 

concentration of 0.74 mg/ml docetaxel is not exceeded. 

• Mix the infusion bag or bottle manually using a rocking motion. 

• From a microbiological point of view, reconstitution /dilution must take place in controlled and 
aseptic conditions and the infusion solution should be used immediately. If not used immediately, 

in-use storage times and conditions are the responsibility of the user. 

Once added as recommended into the infusion bag, the docetaxel infusion solution, if stored below 

25°C, is stable for 6 hours. It should be used within 6 hours (including the one hour infusion 

intravenous administration). 

Docetaxel infusion solution is supersaturated, therefore may crystallize over time. If crystals 

appear, the solution must no longer be used and shall be discarded. 

• As with all parenteral products, infusion solution should be visually inspected prior to use, 
solutions containing a precipitate should be discarded. 

 

Disposal 

All materials that have been utilised for dilution and administration should be disposed of according to 

standard procedures. Do not throw away any medicines via wastewater. Ask your pharmacist how to 

throw away medicines you no longer use. These measures will help protect the environment. 



279 

Package leaflet: Information for the patient 

 

DOCETAXEL KABI 180 mg/9 ml concentrate for solution for infusion 

docetaxel 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor, hospital pharmacist or nurse. 

- If you get any side effects, talk to your doctor, hospital pharmacist or nurse. This includes any 
 possible side effects not listed in this leaflet. See section 4. 

 

What is in this leaflet: 

 

1. What DOCETAXEL KABI is and what it is used for 

2.  What you need to know before you use DOCETAXEL KABI 

3.  How to use DOCETAXEL KABI 

4.  Possible side effects 

5.  How to store DOCETAXEL KABI 

6.  Contents of the pack and other information 

 

 

1. What DOCETAXEL KABI is and what it is used for 
 

The name of this medicine is DOCETAXEL KABI. Its common name is docetaxel. Docetaxel is a 

substance derived from the needles of yew trees. 

Docetaxel belongs to the group of anti-cancer medicines called taxoids. 

 

DOCETAXEL KABI has been prescribed by your doctor for the treatment of breast cancer, special 

forms of lung cancer (non-small cell lung cancer), prostate cancer, gastric cancer or head and neck 

cancer: 

- For the treatment of advanced breast cancer, DOCETAXEL KABI could be administered either 
alone or in combination with doxorubicin, or trastuzumab, or capecitabine. 

- For the treatment of early breast cancer with or without lymph node involvement, DOCETAXEL 
KABI could be administered in combination with doxorubicin and cyclophosphamide. 

- For the treatment of lung cancer, DOCETAXEL KABI could be administered either alone or in 
combination with cisplatin. 

- For the treatment of prostate cancer, DOCETAXEL KABI is administered in combination with 
prednisone or prednisolone. 

- For the treatment of metastatic gastric cancer, DOCETAXEL KABI is administered in 
combination with cisplatin and 5-fluorouracil. 

- For the treatment of head and neck cancer, DOCETAXEL KABI is administered in combination 
with cisplatin and 5-fluorouracil. 

 

 

2. What you need to know before you use DOCETAXEL KABI  
 

You must not be given DOCETAXEL KABI: 

 

• if you are allergic (hypersensitive) to docetaxel or any of the other ingredients of DOCETAXEL 
KABI (listed in section 6). 

• if the number of white blood cells is too low. 

• if you have a severe liver disease. 



280 

Warnings and precautions 

 

Before each treatment with DOCETAXEL KABI, you will have blood tests to check that you have 

enough blood cells and sufficient liver function to receive DOCETAXEL KABI. In case of white 

blood cells disturbances, you may experience associated fever or infections. 

 

Tell your doctor, hospital pharmacist, or nurse immediately if you have abdominal pain or tenderness, 

diarrhoea, rectal haemorrhage, blood in stool or fever. These symptoms may be the first signs of a 

serious gastrointestinal toxicity, which could be fatal. Your doctor should address them immediately. 

 

Tell your doctor, hospital pharmacist or nurse if you have vision problems. In case of vision 

problems, in particular blurred vision, you should immediately have your eyes and vision examined.  

 

Tell your doctor, hospital pharmacist or nurse if you have experienced an allergic reaction to previous 

paclitaxel therapy. 

 

Tell your doctor, hospital pharmacist or nurse if you have heart problems. 

 

If you develop acute or worsening problems with your lungs (fever, shortness of breath or cough), 

please tell your doctor, hospital pharmacist or nurse immediately. Your doctor may stop your 

treatment immediately. 

 

You will be asked to take premedication consisting of an oral corticosteroid such as dexamethasone, 

one day prior to DOCETAXEL KABI administration and to continue for one or two days after it in 

order to minimise certain undesirable effects which may occur after the infusion of DOCETAXEL 

KABI in particular allergic reactions and fluid retention (swelling of the hands, feet, legs or weight 

gain). 

 

During treatment, you may be given other medicines to maintain the number of your blood cells. 

 

Severe skin problems such as Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), 

Acute Generalized Exanthematous Pustulosis (AGEP) have been reported with DOCETAXEL KABI:  

- SJS/TEN symptoms may include blistering, peeling or bleeding on any part of your skin 
(including your lips, eyes, mouth, nose, genitals, hands or feet) with or without a rash. You 

may also have flu-like symptoms at the same time, such as fever, chills or aching muscles. 

- AGEP symptoms may include a red, scaly widespread rash with bumps under the swollen skin 
(including your skin folds, trunk, and upper extremities) and blisters accompanied by fever.  

If you develop severe skin reactions or any of the reactions listed above, immediately contact your 

doctor or healthcare professional. 

 

DOCETAXEL KABI contains alcohol. Discuss with your doctor if you suffer from alcohol 

dependency, epilepsy or liver impairment. See also section “DOCETAXEL KABI contains ethanol 

(alcohol)” below.  

 

Other medicines and DOCETAXEL KABI 
 

Please tell your doctor or hospital pharmacist if you are taking or have recently taken any other 

medicine, including medicines obtained without a prescription. This is because DOCETAXEL KABI 

or the other medicine may not work as well as expected and you may be more likely to get a side 

effect. The amount of alcohol in this medicinal product may alter the effects of other medicines. 

 

Pregnancy, breast-feeding and fertility 

 

Ask your doctor for advice before being given any medicine. 

 

DOCETAXEL KABI must NOT be administered if you are pregnant unless clearly indicated by your 

doctor. 



281 

 

You must not become pregnant during treatment with this medicine and must use an effective method 

of contraception during therapy, because DOCETAXEL KABI may be harmful for the unborn baby. If 

pregnancy occurs during your treatment, you must immediately inform your doctor. 

 

You must not breast-feed while you are treated with DOCETAXEL KABI. 

 

If you are a man being treated with DOCETAXEL KABI you are advised not to father a child during 

and up to 6 months after treatment and to seek advice on conservation of sperm prior to treatment 

because docetaxel may alter male fertility. 

 

Driving and using machines 

 

The amount of alcohol in this medicinal product may impair your ability to drive or use machines. 

You may experience side effects of this medicine that may impair your ability to drive, use tools or 

operate machines (see section 4 Possible side effects). If this happens, do not drive or use any tools or 

machines before discussing with your doctor, nurse or hospital pharmacist. 
 

DOCETAXEL KABI contains ethanol (alcohol). 

 

This medicine contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 3.55 g ethanol anhydrous per 

vial, equivalent to 90 ml of beer or 36 ml wine. 

Harmful for those suffering from alcoholism. 

To be taken into account in pregnant or breast-feeding women, in children and high-risk groups such 

as patients with liver disease, or epilepsy. 

 

The amount of alcohol in this medicine may have effects on the central nervous system (the part of the 

nervous system that includes the brain and spinal cord). 

 

 

3. How to use DOCETAXEL KABI  
 

DOCETAXEL KABI will be administered to you by a healthcare professional. 

 

Usual dose 

 

The dose will depend on your weight and your general condition. Your doctor will calculate your body 

surface area in square meters (m²) and will determine the dose you should receive. 

 

Method and route of administration 

 

DOCETAXEL KABI will be given by infusion into one of your veins (intravenous use). The infusion 

will last approximately one hour during which you will be in the hospital. 

 

Frequency of administration 

 

You should usually receive your infusion once every 3 weeks. 

 

Your doctor may change the dose and frequency of dosing depending on your blood tests, your general 

condition and your response to DOCETAXEL KABI. In particular, please inform your doctor in case 

of diarrhoea, sores in the mouth, feeling of numbness or pins and needles, fever and give her/him 

results of your blood tests. Such information will allow her/him to decide whether a dose reduction is 

needed. If you have any further questions on the use of this medicine, ask your doctor, or hospital 

pharmacist. 

 

 

 



282 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Your doctor will discuss these with you and will explain the potential risks and benefits of your 

treatment. 

 

The most commonly reported adverse reactions of DOCETAXEL KABI alone are: decrease in the 

number of red blood cells or white blood cells, alopecia, nausea, vomiting, sores in the mouth, 

diarrhoea and tiredness. 

 

The severity of adverse events of DOCETAXEL KABI may be increased when DOCETAXEL KABI 

is given in combination with other chemotherapeutic agents. 

 

During the infusion at the hospital the following allergic reactions may occur (may affect more than 1 
in 10 people): 

• flushing, skin reactions, itching 

• chest tightness; difficulty in breathing 

• fever or chills 

• back pain 

• low blood pressure. 
More severe reactions may occur. 

If you had an allergic reaction to paclitaxel, you may also experience an allergic reaction to docetaxel, 

which may be more severe. 

 

The hospital staff will monitor your condition closely during treatment. Tell them immediately if you 

notice any of these effects. 

 

Between infusions of DOCETAXEL KABI the following may occur, and the frequency may vary with 

the combinations of medicines that are received 

 

Very common (may affect more than 1 in 10 people): 

• infections, decrease in the number of red (anaemia), or white blood cells (which are important in 
fighting infection) and platelets 

• fever: if this happens you must tell your doctor immediately 

• allergic reactions as described above 

• loss of appetite (anorexia) 

• insomnia 

• feeling of numbness or pins and needles or pain in the joints or muscles 

• headache 

• alteration in sense of taste 

• inflammation of the eye or increased tearing of the eyes 

• swelling caused by faulty lymphatic drainage 

• shortness of breath 

• nasal drainage; inflammation of the throat and nose; cough 

• bleeding from the nose 

• sores in the mouth 

• stomach upsets including nausea, vomiting and diarrhoea, constipation 

• abdominal pain 

• indigestion 

• hair loss: in most cases normal hair growth should return. In some cases (frequency not known) 
permanent hair loss has been observed 

• redness and swelling of the palms of your hands or soles of your feet which may cause your skin to 
peel (this may also occur on the arms, face, or body) 

• change in the colour of your nails, which may detach 



283 

• muscle aches and pains; back pain or bone pain 

• change or absence of menstrual period 

• swelling of the hands, feet, legs 

• tiredness; or flu-like symptoms 

• weight gain or loss. 

• infection of the upper respiratory tract. 
 

Common (may affect up to 1 in 10 people): 

• oral candidiasis 

• dehydration 

• dizziness 

• hearing impaired 

• decrease in blood pressure; irregular or rapid heart beat 

• heart failure 

• oesophagitis 

• dry mouth 

• difficulty or painful swallowing 

• haemorrhage 

• raised liver enzymes (hence the need for regular blood tests). 

• rises in blood sugar levels (diabetes) 

• decrease of the potassium, calcium and/or phosphate in your blood.  
 

Uncommon (may affect up to 1 in 100 people): 

• fainting 

• at the injection site, skin reactions, phlebitis (inflammation of the vein) or swelling 

• blood clots. 

• acute myeloid leukemia and myelodysplastic syndrome (types of blood cancer) may occur in 
patients who are treated with docetaxel together with certain other anticancer treatments. 

 

Rare (may affect up to 1 in 1,000 people): 

• inflammation of the colon, small intestine, which could be fatal (frequency not known); intestinal 
perforation. 

 

Frequency not known (cannot be estimated from the available data): 

• interstitial lung disease (inflammation of the lungs causing coughing and difficulty breathing. 
Inflammation of the lungs can also develop when docetaxel therapy is used with radiotherapy) 

• pneumonia (infection of the lungs) 

• pulmonary fibrosis (scarring and thickening in the lungs with shortness of breath). 

• blurred vision due to swelling of the retina within the eye (cystoid macular oedema) 

• decrease of the sodium and/or magnesium in your blood (electrolyte balance disorders). 
• ventricular arrhythmia or ventricular tachycardia (manifested as irregular and/or rapid heartbeat, 

severe shortness of breath, dizziness, and/or fainting). Some of these symptoms can be serious. If 

this happens, you must tell your doctor immediately 

• injection site reactions at the site of a previous reaction. 

• non-Hodgkin lymphoma (a cancer affecting the immune system) and other cancers may occur in 
patients who are treated with docetaxel together with certain other anticancer treatments. 

• Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) (blistering, 
peeling or bleeding on any part of your skin (including your lips, eyes, mouth, nose, 

genitals, hands or feet) with or without a rash. You may also have flu-like symptoms at the 

same time, such as fever, chills or aching muscles.) 

• Acute Generalized Exanthematous Pustulosis (AGEP) (red, scaly widespread rash with 
bumps under the swollen skin (including your skin folds, trunk, and upper extremities) and 

blisters accompanied by fever.) 
 



284 

Reporting of adverse effects 

If you get any side effects, talk to your doctor, hospital pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. You can also report side effects directly via the national reporting 

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 

 

5. How to store DOCETAXEL KABI  
 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the outer carton and on the label of 

the vial after Exp. The expiry date refers to the last day of that month. 

 

Do not store above 25°C. 

Store in the original package in order to protect from light. 

 

Use the vial immediately after its opening. If not used immediately, in-use storage times and 

conditions are the responsibility of the user.  

 

From a microbiological point of view, reconstitution/dilution must take place in controlled and aseptic 

conditions. 

 

Use immediately the medicine once added into the infusion bag. If not used immediately, in-use 

storage times and conditions are the responsibility of the user and would normally not be longer than 6 

hours below 25°C including the one hour infusion. 

 

Docetaxel infusion solution is supersaturated, therefore may cristallize over time. If crystals appear, 

the solution must no longer be used and shall be discarded. 

 

Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines 

you no longer use. These measures will help protect the environment 

 

 

6. Contents of the pack and other information 
 

What DOCETAXEL KABI contains 

- The active substance is docetaxel anhydrous. Each ml of concentrate for solution for infusion 
contains 20 mg docetaxel. 

- The other ingredients are polysorbate 80, ethanol anhydrous (see section 2) and anhydrous citric 
acid (for pH adjustment). 

 

What DOCETAXEL KABI looks like and contents of the pack 

DOCETAXEL KABI concentrate for solution for infusion is a clear, colourless to pale yellow 

solution. 

 

10 ml clear, colourless Type-I glass vial, closed with flurotec rubber stopper and a orange flip-off 

aluminium over seal containing 9 ml of concentrate. 

 

Each box contains one vial of 9 ml concentrate (180 mg docetaxel). 

 

Marketing Authorisation Holder  

Fresenius Kabi Deutschland GmbH 

Else-Kröner-Straße 1, 

61352 Bad Homburg v.d.Höhe 

Germany 

 



285 

Manufacturer 

Fresenius Kabi Deutschland GmbH 

Pfingstweide 53 

61169 Friedberg 

Germany  

 

Or 

 
Fresenius Kabi Oncology Plc. 

Lion Court, Farnham Road, Bordon 

Hampshire, GU35 0NF 

United Kingdom 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

This leaflet was last revised in {MM/YYYY} 



286 

The following information is intended for healthcare professionals only: 

 

PREPARATION GUIDE FOR USE WITH DOCETAXEL KABI 180 mg/9 ml 

CONCENTRATE FOR SOLUTION FOR INFUSION  

 

 

It is important that you read the entire contents of this guide prior to the preparation of the 

DOCETAXEL KABI infusion solution. 

 

Recommendations for the safe handling 

Docetaxel is an antineoplastic agent and, as with other potentially toxic compounds, caution should be 

exercised when handling it and preparing its solutions. The use of gloves is recommended. 

 

If DOCETAXEL KABI concentrate or infusion solution should come into contact with skin, wash 

immediately and thoroughly with soap and water. If it should come into contact with mucous 

membranes, wash immediately and thoroughly with water. 

 

Preparation of the intravenous administration 

 

Preparation of the infusion solution 

DO NOT use other docetaxel medicine consisting of 2 vials (concentrate and solvent) with this 

medicine (DOCETAXEL KABI 180 mg/9 ml concentrate for solution for infusion, which 

contains only 1 vial). 

 

DOCETAXEL KABI 180 mg/9 ml concentrate for solution for infusion requires NO prior 

dilution with a solvent and is ready to add to the infusion solution. 

• Each vial is for single use and should be used immediately after opening. If not used immediately, 
in-use storage times and conditions are the responsibility of the user. More than one vial of 

concentrate for solution for infusion may be necessary to obtain the required dose for the patient. 

For example, a dose of 140 mg docetaxel would require 7 ml docetaxel concentrate for solution. 

• Aseptically withdraw the required amount of concentrate for solution for infusion with a calibrated 
syringe. 

In DOCETAXEL KABI 180 mg/9 ml vial the concentration of docetaxel is 20 mg/ml. 

• Then, inject via a single injection (one shot) into a 250 ml infusion bag or bottle containing either 
5% glucose solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. If a dose greater 

than 190 mg of docetaxel is required, use a larger volume of the infusion vehicle so that a 

concentration of 0.74 mg/ml docetaxel is not exceeded. 

• Mix the infusion bag or bottle manually using a rocking motion. 

• From a microbiological point of view, reconstitution /dilution must take place in controlled and 
aseptic conditions and the infusion solution should be used immediately. If not used immediately, 

in-use storage times and conditions are the responsibility of the user. 

Once added as recommended into the infusion bag, the docetaxel infusion solution, if stored below 

25°C, is stable for 6 hours. It should be used within 6 hours (including the one hour infusion 

intravenous administration). 

Docetaxel infusion solution is supersaturated, therefore may crystallize over time. If crystals 

appear, the solution must no longer be used and shall be discarded. 

• As with all parenteral products, infusion solution should be visually inspected prior to use, 
solutions containing a precipitate should be discarded. 

 

Disposal 

All materials that have been utilised for dilution and administration should be disposed of according to 

standard procedures. Do not throw away any medicines via wastewater. Ask your pharmacist how to 

throw away medicines you no longer use. These measures will help protect the environment. 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET