Docetaxel Teva

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Docetaxel Teva 20 mg/0.72 ml concentrate and solvent for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each vial of Docetaxel Teva 20 mg/0.72 ml concentrate contains 20 mg docetaxel. Each ml of 
concentrate contains 27.73 mg docetaxel. 
 
Excipients with known effect:  
Each vial of concentrate contains 25.1% (w/w) anhydrous ethanol (181 mg of anhydrous ethanol). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate and solvent for solution for infusion. 
The concentrate is a clear viscous, yellow to brown-yellow solution. 
The solvent is a colourless solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Breast cancer 
 
Docetaxel Teva 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 Teva 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 Teva 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 Teva 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 Teva 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. 
 
Non-small cell lung cancer 
 



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Docetaxel Teva is indicated for the treatment of patients with locally advanced or metastatic non-small 
cell lung cancer after failure of prior chemotherapy. 
 
Docetaxel Teva 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 Teva in combination with prednisone or prednisolone is indicated for the treatment of 
patients with hormone refractory metastatic prostate cancer. 
 
Gastric adenocarcinoma 
 
Docetaxel Teva 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 Teva 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 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). 
 
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). 
 
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. 



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In combination with capecitabine, the recommended dose of docetaxel is 75 mg/m2 every three weeks, 
combined with capecitabine at 1,250 mg/m2 twice daily (within 30 minutes after a meal) for 2 weeks 
followed by a 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 
The recommended dose of docetaxel is 75 mg/m2. Prednisone or prednisolone 5 mg orally twice daily 
is administered continuously (see section 5.1). 
 
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. 

 
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 



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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%.  

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. 
 



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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 Teva 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 Teva 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. 
 
Docetaxel must not be used in patients with baseline neutrophil count of <1,500 cells/mm3. 
 
Docetaxel must not be used in patients with severe liver impairment since there is no data available 
(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 
 



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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, 
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). 
 
Fluid retention 
 
Patients with severe fluid retention such as pleural effusion, pericardial effusion and ascites should be 
monitored closely. 
 
Respiratory disorders 



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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. 
 
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 



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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) 
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 
There are limited data available in patients > 70 years of age on docetaxel use in combination with 
doxorubicin and cyclophosphamide. 
 
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. 
 
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. 



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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. 
Older people treated with TCF should be closely monitored. 
 
Excipients 
 
This medicinal product contains 25.1 % (w/w) ethanol, anhydrous (alcohol), i.e. up to 181 mg ethanol, 
anhydrous per concentrate vial, equivalent to 4.6 ml beer or 1.9 ml wine. 
 
Harmful for those suffering from alcoholism. 
To be taken into account in pregnant or breastfeeding 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. 
 
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 
 
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. As with other 



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cytotoxic medicinal products, docetaxel may cause foetal harm when administered to pregnant 
women. Therefore, docetaxel must not be used during pregnancy unless clearly indicated.  
 
Women of childbearing age receiving docetaxel should be advised to avoid becoming pregnant, and to 
inform the treating physician immediately should this occur. 
 
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. 
 
Contraception in males and females 
 
An effective method of contraception should be used during treatment. 
 
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 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). 

 
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: 



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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 the 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. 
 
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). 
 
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 100 mg/m² single agent 



13 

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%) 

 

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 
phosphatase increased 
(< 4%);  
G3/4 AST increased 

 



14 

MedDRA system 
organ classes  

Very common adverse 
reactions  

Common adverse 
reactions   

Uncommon adverse 
reactions  

(< 3%); 
G3/4 ALT increased 
(< 2%) 

 
Description of selected adverse reactions in breast cancer for Docetaxel 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 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 

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%) 

 



15 

Tabulated list of adverse reactions in breast cancer for Docetaxel 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) 

  

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 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%)   



16 

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 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 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 

 



17 

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  
 
Description of selected adverse reactions in breast cancer for Docetaxel 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 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%); 

Abdominal pain upper; 
Dry mouth 



18 

Vomiting (G3/4: 4%); 
Constipation (G3/4: 1%); 
Abdominal pain (G3/4: 2%); 
Dyspepsia 

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%); 
Oedema peripheral (G3/4: 1%) 

Lethargy; 
Pain 

Investigations  Weight decreased; 
G3/4 Blood bilirubin increased 
(9%) 

 
Tabulated list of adverse reactions in prostate cancer for Docetaxel 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 
tissue 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%) 

 

 
Tabulated list of adverse reactions for adjuvant therapy with Docetaxel 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 



19 

 
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 system 
and breast disorders 
 

Amenorrhoea (G3/4: 
NA) 

  



20 

MedDRA system 
organ classes 

Very common 
adverse reactions  

Common adverse 
reactions 

Uncommon adverse 
reactions 

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 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 
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%) 



21 

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 in 19 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) 
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) 



22 

 
Tabulated list of adverse reactions in gastric adenocarcinoma cancer for Docetaxel 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 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 
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 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,  Cancer pain (G3/4:  



23 

malignant and 
unspecified (incl cysts 
and polyps) 

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%) 

 

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 Neutropenia (G3/4:   



24 

system disorders 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%); 
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 and 
connective tissue 
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. 
 



25 

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. 
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 
Very rare cases of cutaneous lupus erythematosus and bullous eruptions such as erythema multiforme, 
Stevens-Johnson syndrome, toxic epidermal necrolysis, have been reported with docetaxel. In some 
cases concomitant factors may have contributed to the development of these effects. 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 gastro-
intestinal disorders. 
 



26 

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. 
 
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: Taxanes, ATC Code: L01CD 02 
 
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 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


27 

 
Docetaxel 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+), 
1,491 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 cyclophosphamide 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 
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 745 0.80 0.68-0.93 0.0043 0.74 0.61-0.90 0.0020 
1-3 467 0.72 0.58-0.91 0.0047 0.62 0.46-0.82 0.0008 
4+ 278 0.87 0.70-1.09 0.2290 0.87 0.67-1.12 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 for the adjuvant 
treatment of patients with operable node-negative breast cancer eligible to receive chemotherapy. 
1,060 patients were randomised to receive either Docetaxel 75 mg/m2 administered 1-hour after 



28 

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 was administered as a 1-hour infusion, all other medicinal 
products 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. 
 
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 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    



29 

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 
*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 cyclophospamide 
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 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). 
 



30 

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). 
More grade 3/4 adverse events were observed for docetaxel monotherapy (55.4%) compared to 
paclitaxel (23.0%). 
 
Docetaxel 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 anemia (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 in combination with trastuzumab 
 
Docetaxel in combination with trastuzumab was studied for the treatment of patients with metastatic 
breast cancer whose tumours over express 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 trastuzumab
1 

n=92 
Docetaxel1 

n=94 
Response rate 
(95% CI) 

61% 
(50-71) 

34% 
(25-45) 

Median duration of response 11.4  5.1 



31 

(months) 
(95% CI) 

(9.2-15.0) (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) 
2Estimated median survival 
 
Docetaxel 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 (1,250 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 medications (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 in combination with platinum agents in chemotherapy-naïve patients 
 
In a phase III study, 1,218 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): 

   



32 

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] 
*: 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 
 
The safety and efficacy of docetaxel in combination with prednisone or prednisolone in patients with 
hormone refractory metastatic prostate cancer were evaluated in a randomised multi-centre phase III 
study. A total of 1,006 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 141 134 137 



33 

Tumour response rate (%) 
95% CI 
p-value* 

12.1 
(7.2-18.6) 

0.1112 

8.2 
(4.2-14.2) 

0.5853 

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. 
 
No statistical differences were observed between treatment groups for Global Quality of Life. 
 
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 (1,000 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) 

5.6 
(4.86-5.91) 

3.7 
(3.45-4.47) 

Hazard ratio 
(95% CI) 
*p-value 

1.473 
(1.189-1.825) 

0.0004 
Median survival (months)  
(95% CI) 
2-year estimate (%) 

9.2 
(8.38-10.58) 

18.4 

8.6 
(7.16-9.46) 

8.8 
Hazard ratio 
(95% CI) 
*p-value 

1.293 
(1.041-1.606) 

0.0201 
Overall response rate (CR+PR) (%) 36.7 25.4 
p-value 0.0106 
Progressive disease as best overall 
Response (%) 

16.7 25.9 

*Unstratified log rank 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. 
 



34 

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) 

11.4 
(10.1-14.0) 

8.3 
(7.4-9.1) 

Adjusted hazard ratio  
(95% CI) 
*p-value 

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) 

Hazard ratio 
(95% CI) 
**p-value 

0.72 
(0.56-0.93) 

0.0128 
Best overall response to chemotherapy (%) 
(95% CI) 

67.8 
(60.4-74.6) 

53.6 
(46.0-61.0) 

***p-value 0.006 
Best overall response to study treatment   



35 

[chemotherapy +/- radiotherapy] (%) 
(95% CI) 

72.3 
(65.1-78.8) 

58.6 
(51.0-65.8) 

***p-value 0.006 
Median duration of response to 
chemotherapy ± radiotherapy (months) 
(95% CI) 

n=128 
15.7 

(13.4-24.6) 

n=106 
11.7 

(10.2-17.4) 
Hazard ratio 
(95% CI) 
**p-value 

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) 
**Log rank 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) 1,000 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) 1,000 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 



36 

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) 

70.6 
(49.0-NA) 

30.1 
(20.9-51.5) 

Hazard ratio  
(95% CI) 
*p-value 

0.70 
(0.54-0.90) 

0.0058 
Median PFS (months)  
(95% CI) 

35.5 
(19.3-NA) 

13.1 
(10.6-20.2) 

Hazard ratio 
(95% CI) 
**p-value 

0.71 
(0.56-0.90) 

0.004 
Best overall response (CR + PR) to 
chemotherapy (%) 
(95%CI) 

71.8 
(65.8-77.2) 

64.2 
(57.9-70.2) 

***p-value 0.070 
Best overall response (CR + PR) to study 
treatment [chemotherapy +/- 
chemoradiotherapy] (%) 
(95%CI) 

 
76.5 

(70.8-81.5) 

 
71.5 

(65.5-77.1) 

***p-value 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 
 
Paediatric Population  
 
The European Medicines Agency has waived the obligation to submit the results of studies with the 
reference medicinal product containing docetaxel in all subsets of the paediatric population in breast 
cancer, non-small cell lung cancer, prostated cancer, gastric carcinoma and head and neck cancer, not 
including type II and III less differentiated nasopharyngeal carcinoma (see section 4.2 for information 
on paediatric use). 
 
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 



37 

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 coadministration. 
 
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 



38 

 
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. 
 
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 
 
Concentrate vial:  
Polysorbate 80 
Ethanol, anhydrous 
 
Solvent vial:  
Water for injections 
 
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 
 
• 18 months. 
• Premix solution: Chemical and physical in-use stability has been demonstrated for 8 hours when 

stored either between 2°C and 8°C or at room temperature (below 25°C). From a 
microbiological point of view, the product should be used immediately. If not used immediately, 
in-use storage times and conditions prior to use are the responsibility of the user and would 
normally not be longer than 24 hours at 2 to 8°C, unless dilution has taken place in controlled 
and validated aseptic conditions. 

• Infusion solution: Chemical and physical in-use stability has been demonstrated for 4 hours at 
room temperature (below 25°C). From a microbiological point of view, the product should be 
used immediately. If not used immediately, in-use storage times and conditions prior to use are 
the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless 
dilution has taken place in controlled and validated aseptic conditions. 

 
6.4 Special precautions for storage 
 

Do not store above 25°C. 
Do not freeze. 
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  
 
Each carton contains: 
• One vial of concentrate and, 
• One vial of solvent 
 



39 

• Docetaxel Teva 20 mg/0.72 ml concentrate for solution for infusion vial  
6 ml clear glass Type I vial with a bromobutyl rubber stopper and a flip-off cap. 

 
This vial contains 0.72 ml of a 27.73 mg/ml solution of docetaxel in polysorbate 80 (fill volume: 
24.4 mg/0.88 ml). This fill volume has been established during the development of docetaxel to 
compensate for liquid loss during preparation of the premix due to foaming, adhesion to the 
walls of the vial and "dead-volume". This overfill ensures that after dilution with the entire 
contents of the accompanying solvent for docetaxel vial, there is a minimal extractable premix 
volume of 2 ml containing 10 mg/ml docetaxel which corresponds to the labelled amount of 
20 mg/0.72 ml per vial. 

 
Solvent vial 
6 ml clear glass Type I vial with a bromobutyl rubber stopper and a flip-off cap. 
 
Solvent vial contains 1.28 ml of water for injections (fill volume: 1.71 ml). The addition of the 
entire contents of the solvent vial to the contents of the Docetaxel Teva 20 mg/0.72 ml 
concentrate for solution for infusion vial ensures a premix concentration of 10 mg/ml docetaxel. 

 
6.6 Special precautions for disposal and other handling 
 
Docetaxel Teva is an antineoplastic agent and, as with other potentially toxic compounds, caution 
should be exercised when handling it and preparing Docetaxel solutions. The use of gloves is 
recommended. 
 
If Docetaxel Teva concentrate, premix solution or infusion solution should come into contact with 
skin, wash immediately and thoroughly with soap and water. If Docetaxel concentrate, premix solution 
or infusion solution should come into contact with mucous membranes, wash immediately and 
thoroughly with water. 
 
Preparation for the intravenous administration 

a) Preparation of the Docetaxel Teva premix solution (10 mg docetaxel/ml) 

If the vials are stored under refrigeration, allow the required number of Docetaxel Teva boxes to stand 
at room temperature (below 25°C) for 5 minutes. 
 
Using a syringe fitted with a needle, aseptically withdraw the entire contents of the solvent for 
Docetaxel Teva vial by partially inverting the vial. 
 
Inject the entire contents of the syringe into the corresponding Docetaxel Teva vial. 
 
Remove the syringe and needle and mix manually by repeated inversions for at least 45 seconds. Do 
not shake. 
 
Allow the premix vial to stand for 5 minutes at room temperature (below 25°C) and then check that 
the solution is homogenous and clear (foaming is normal even after 5 minutes due to the presence of 
polysorbate 80 in the formulation). 
 
The premix solution contains 10 mg/ml docetaxel and should be used immediately after preparation. 
However the chemical and physical stability of the premix solution has been demonstrated for 8 hours 
when stored either between 2°C and 8°C or at room temperature (below 25°C). 
 
b) Preparation of the infusion solution 

More than one premix vial may be necessary to obtain the required dose for the patient. Based on the 
required dose for the patient expressed in mg, aseptically withdraw the corresponding premix volume 
containing 10 mg/ml docetaxel from the appropriate number of premix vials using graduated syringes 



40 

fitted with a needle. For example, a dose of 140 mg docetaxel would require 14 ml docetaxel premix 
solution. 
 
Inject the required premix volume into a non-PVC 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 200 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 Docetaxel Teva infusion solution should be used within 4 hours and should be aseptically 
administered as a 1-hour infusion under room temperature (below 25°C) and normal lighting 
conditions. 
 
As with all parenteral products, Docetaxel Teva premix solution and infusion solution should be 
visually inspected prior to use, solutions containing a precipitate should be discarded. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Teva B.V. 
Swensweg 5 
2031 GA Haarlem 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/611/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 26 January 2010 
Date of latest renewal: 22 May 2014 
 
 
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 



41 

1. NAME OF THE MEDICINAL PRODUCT 
 
Docetaxel Teva 80 mg/2.88 ml concentrate and solvent for solution for infusion 
 

 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each vial of Docetaxel Teva 80 mg/2.88 ml concentrate contains 80 mg docetaxel. Each ml of 
concentrate contains 27.73 mg docetaxel. 
 
Excipients with known effect:  
Each vial of concentrate contains 25.1% (w/w) anhydrous ethanol (723 mg of anhydrous ethanol).   
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 

Concentrate and solvent for solution for infusion. 
The concentrate is a clear viscous, yellow to brown-yellow solution. 
The solvent is a colourless solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Breast cancer 
 
Docetaxel Teva 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 Teva 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 Teva 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 Teva 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 Teva 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. 
 
Non-small cell lung cancer 
 



42 

Docetaxel Teva is indicated for the treatment of patients with locally advanced or metastatic non-small 
cell lung cancer after failure of prior chemotherapy. 
 
Docetaxel Teva 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 Teva in combination with prednisone or prednisolone is indicated for the treatment of 
patients with hormone refractory metastatic prostate cancer. 
 
Gastric adenocarcinoma 
 
Docetaxel Teva 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 Teva 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 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). 
 
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). 
 
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. 



43 

 
In combination with capecitabine, the recommended dose of docetaxel is 75 mg/m2 every three weeks, 
combined with capecitabine at 1,250 mg/m2 twice daily (within 30 minutes after a meal) for 2 weeks 
followed by a 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 
The recommended dose of docetaxel is 75 mg/m2. Prednisone or prednisolone 5 mg orally twice daily 
is administered continuously (see section 5.1). 
 
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. 

 
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 



44 

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%.  

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. 
 



45 

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 Teva 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 Teva 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. 
 
Docetaxel must not be used in patients with baseline neutrophil count of <1,500 cells/mm3. 
 
Docetaxel must not be used in patients with severe liver impairment since there is no data available 
(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 
 



46 

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, 
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). 
 
Fluid retention 
 
Patients with severe fluid retention such as pleural effusion, pericardial effusion and ascites should be 
monitored closely. 
 
Respiratory disorders 



47 

 
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. 
 
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 



48 

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) 
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 
There are limited data available in patients > 70 years of age on docetaxel use in combination with 
doxorubicin and cyclophosphamide. 
 
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. 
 
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. 



49 

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. 
Older people treated with TCF should be closely monitored. 
 
Excipients 
 
This medicinal product contains 25.1 % (w/w) ethanol, anhydrous (alcohol), i.e. up to 723 mg ethanol, 
anhydrous per concentrate vial, equivalent to 18.3 ml beer or 7.6 ml wine. 
 
Harmful for those suffering from alcoholism. 
To be taken into account in pregnant or breastfeeding 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. 
 
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 
 
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. As with other 



50 

cytotoxic medicinal products, docetaxel may cause foetal harm when administered to pregnant 
women. Therefore, docetaxel must not be used during pregnancy unless clearly indicated.  
 
Women of childbearing age receiving docetaxel should be advised to avoid becoming pregnant, and to 
inform the treating physician immediately should this occur. 
 
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. 
 
Contraception in males and females 
 
An effective method of contraception should be used during treatment. 
 
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 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). 

 
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: 



51 

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 the 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. 
 
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). 
 
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 100 mg/m² single agent 
MedDRA system 
organ classes  

Very common adverse 
reactions  

Common adverse 
reactions   

Uncommon adverse 
reactions  



52 

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%) 

 

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 
phosphatase increased 

 



53 

MedDRA system 
organ classes  

Very common adverse 
reactions  

Common adverse 
reactions   

Uncommon adverse 
reactions  

(< 4%);  
G3/4 AST increased 
(< 3%); 
G3/4 ALT increased 
(< 2%) 

 
Description of selected adverse reactions in breast cancer for Docetaxel 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 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 

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%) 



54 

 

Tabulated list of adverse reactions in breast cancer for Docetaxel 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) 

  

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%) 

 



55 

Tabulated list of adverse reactions in non-small cell lung cancer for Docetaxel 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 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 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 

 



56 

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  
 
Description of selected adverse reactions in breast cancer for Docetaxel 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 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%); 



57 

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%); 
Oedema peripheral (G3/4: 1%) 

Lethargy; 
Pain 

Investigations  Weight decreased; 
G3/4 Blood bilirubin increased 
(9%) 

 
Tabulated list of adverse reactions in prostate cancer for Docetaxel 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%) 



58 

 
Musculoskeletal and connective 
tissue 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%) 

 

 

Tabulated list of adverse reactions in breast cancer for adjuvant therapy with Docetaxel 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 
 
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: 

  



59 

MedDRA system 
organ classes 

Very common 
adverse reactions   

Common adverse 
reactions 

Uncommon adverse 
reactions 

0.4%) 
Musculoskeletal and 
connective tissue 
disorders 

Myalgia (G3/4: 0.7%); 
Arthralgia (G3/4: 
0.2%) 

  

Reproductive system 
and breast disorders 
 

Amenorrhoea (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 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. 
 



60 

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 in 19 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 
With primary 

G-CSF prophylaxis 



61 

(n = 111) 
n (%) 

(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 cancer for Docetaxel 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 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 
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 75 mg/m² in combination 
with cisplatin and 5-fluorouracil 
 



62 

• 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%) 

 

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 



63 

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%); 
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 
and connective 
tissue 
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. 
 



64 

 
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. 
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 
Very rare cases of cutaneous lupus erythematosus and bullous eruptions such as erythema multiforme, 
Stevens-Johnson syndrome, toxic epidermal necrolysis, have been reported with docetaxel. In some 
cases concomitant factors may have contributed to the development of these effects. Scleroderma-like 
changes usually preceded by peripheral lymphoedema have been reported with docetaxel.  Cases of 
permanent alopecia (frequency not known) have been reported. 



65 

 
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 gastro-
intestinal 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. 
 
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: Taxanes, ATC Code: L01CD 02 
 
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 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


66 

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 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+), 
1,491 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 cyclophosphamide 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 
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 745 0.80 0.68-0.93 0.0043 0.74 0.61-0.90 0.0020 
1-3 467 0.72 0.58-0.91 0.0047 0.62 0.46-0.82 0.0008 
4+ 278 0.87 0.70-1.09 0.2290 0.87 0.67-1.12 0.2746 



67 

*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 for the adjuvant 
treatment of patients with operable node-negative breast cancer eligible to receive chemotherapy. 
1,060 patients were randomised to receive either Docetaxel 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 was administered as a 1-hour infusion, all other medicinal 
products were given as 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. 
 
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 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 



68 

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 
*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 chemotherapy a 

    

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 cyclophospamide 
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 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 



69 

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). 
More grade 3/4 adverse events were observed for docetaxel monotherapy (55.4%) compared to 
paclitaxel (23.0%). 
 
Docetaxel 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 anemia (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 in combination with trastuzumab 
 
Docetaxel in combination with trastuzumab was studied for the treatment of patients with metastatic 
breast cancer whose tumours over express 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+, 



70 

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 trastuzumab
1 

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 
 
Docetaxel 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 (1,250 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 medications (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 in combination with platinum agents in chemotherapy-naïve patients 
 
In a phase III study, 1,218 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). 
 



71 

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] 
*: 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 
 
The safety and efficacy of docetaxel in combination with prednisone or prednisolone in patients with 
hormone refractory metastatic prostate cancer were evaluated in a randomised multi-centre phase III 
study. A total of 1,006 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 291 282 300 



72 

PSA** response rate (%) 
95% CI  
p-value* 

45.4 
(39.5-51.3) 

0.0005 

47.9 
(41.9-53.9) 

<0.0001 

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 
Tumour 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. 
 
No statistical differences were observed between treatment groups for Global Quality of Life. 
 
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 (1,000 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) 

5.6 
(4.86-5.91) 

3.7 
(3.45-4.47) 

Hazard ratio 
(95% CI) 
*p-value 

1.473 
(1.189-1.825) 

0.0004 
Median survival (months)  
(95% CI) 
2-year estimate (%) 

9.2 
(8.38-10.58) 

18.4 

8.6 
(7.16-9.46) 

8.8 
Hazard ratio 
(95% CI) 
*p-value 

1.293 
(1.041-1.606) 

0.0201 
Overall response rate (CR+PR) (%) 36.7 25.4 
p-value 0.0106 
Progressive disease as best overall 
Response (%) 

16.7 25.9 

*Unstratified log rank test 



73 

 
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) 

11.4 
(10.1-14.0) 

8.3 
(7.4-9.1) 

Adjusted hazard ratio  
(95% CI) 
*p-value 

0.70 
(0.55-0.89) 

0.0042 
Median survival (months)  18.6 14.5 



74 

(95% CI) (15.7-24.0) (11.6-18.7) 
Hazard ratio 
(95% CI) 
**p-value 

0.72 
(0.56-0.93) 

0.0128 
Best overall response to chemotherapy (%) 
(95%CI) 

67.8 
(60.4-74.6) 

53.6 
(46.0-61.0) 

***p-value 0.006 
Best overall response to study treatment 
[chemotherapy +/- radiotherapy] (%) 
(95%CI) 

 
72.3 

(65.1-78.8) 

 
58.6 

(51.0-65.8) 
***p-value 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) 
**Log rank 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) 1,000 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) 1,000 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 



75 

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) 

70.6 
(49.0-NA) 

30.1 
(20.9-51.5) 

Hazard ratio  
(95% CI) 
*p-value 

0.70 
(0.54-0.90) 

0.0058 
Median PFS (months)  
(95% CI) 

35.5 
(19.3-NA) 

13.1 
(10.6-20.2) 

Hazard ratio 
(95% CI) 
**p-value 

0.71 
(0.56-0.90) 

0.004 
Best overall response (CR + PR) to 
chemotherapy (%) 
(95%CI) 

71.8 
(65.8-77.2) 

64.2 
(57.9-70.2) 

***p-value 0.070 
Best overall response (CR + PR) to study 
treatment [chemotherapy +/- 
chemoradiotherapy] (%) 
(95%CI) 

 
76.5 

(70.8-81.5) 

 
71.5 

(65.5-77.1) 

***p-value 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 
 
Paediatric population 
 
The European Medicines Agency has waived the obligation to submit the results of studies with the 
reference medicinal product containing docetaxel in all subsets of the paediatric population in breast 
cancer, non-small cell lung cancer, prostated cancer, gastric carcinoma and head and neck cancer, not 
including type II and III less differentiated nasopharyngeal carcinoma (see section 4.2 for information 
on paediatric use). 
 
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.  



76 

 
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 coadministration. 
 
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 



77 

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. 
 
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 
 
Concentrate vial:  
Polysorbate 80 
Ethanol, anhydrous 
 
Solvent vial:  
Water for injections 
 
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 
 
• 18 months. 
• Premix solution: Chemical and physical in-use stability has been demonstrated for 8 hours when 

stored either between 2°C and 8°C or at room temperature (below 25°C). From a 
microbiological point of view, the product should be used immediately. If not used immediately, 
in-use storage times and conditions prior to use are the responsibility of the user and would 
normally not be longer than 24 hours at 2 to 8°C, unless dilution has taken place in controlled 
and validated aseptic conditions. 

• Infusion solution: Chemical and physical in-use stability has been demonstrated for 4 hours at 
room temperature (below 25°C). From a microbiological point of view, the product should be 
used immediately. If not used immediately, in-use storage times and conditions prior to use are 
the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless 
dilution has taken place in controlled and validated aseptic conditions. 

 
6.4 Special precautions for storage and other handling 
 

Do not store above 25°C. 
Do not freeze. 
Store in the original package in order to protect from light. 
For storage conditions of the diluted medicinal product, see section 6.3. 

 



78 

6.5 Nature and contents of container 
 
Each carton contains: 
• One vial of concentrate and, 
• One vial of solvent 
 
• Docetaxel Teva 80 mg/2.88 ml concentrate for solution for infusion vial  
 15 ml clear glass Type I vial with a bromobutyl rubber stopper and a flip-off cap. 

 
This vial contains 2.88 ml of a 27.73 mg/ml solution of docetaxel in polysorbate 80 (fill volume: 
94.4 mg/3.40 ml). This fill volume has been established during the development of docetaxel to 
compensate for liquid loss during preparation of the premix due to foaming, adhesion to the 
walls of the vial and "dead-volume". This overfill ensures that after dilution with the entire 
contents of the accompanying solvent for docetaxel vial, there is a minimal extractable premix 
volume of 8 ml containing 10 mg/ml docetaxel which corresponds to the labelled amount of 
80 mg/2.88 ml per vial. 
 
Solvent vial 
15 ml clear glass Type I vial with a bromobutyl rubber stopper and a flip-off cap. 
 
Solvent vial contains 5.12 ml of water for injections (fill volume: 6.29 ml). The addition of the 
entire contents of the solvent vial to the contents of the Docetaxel Teva 80 mg/2.88 ml 
concentrate for solution for infusion vial ensures a premix concentration of 10 mg/ml docetaxel. 

 

6.6 Special precautions for disposal and other handling 
 
Docetaxel Teva is an antineoplastic agent and, as with other potentially toxic compounds, caution 
should be exercised when handling it and preparing Docetaxel solutions. The use of gloves is 
recommended. 
 
If Docetaxel Teva concentrate, premix solution or infusion solution should come into contact with 
skin, wash immediately and thoroughly with soap and water. If Docetaxel concentrate, premix solution 
or infusion solution should come into contact with mucous membranes, wash immediately and 
thoroughly with water. 
 
Preparation for the intravenous administration 

a) Preparation of the Docetaxel Teva premix solution (10 mg docetaxel/ml) 

If the vials are stored under refrigeration, allow the required number of Docetaxel Teva boxes to stand 
at room temperature (below 25°C) for 5 minutes. 
 
Using a syringe fitted with a needle, aseptically withdraw the entire contents of the solvent for 
Docetaxel Teva vial by partially inverting the vial. 
 
Inject the entire contents of the syringe into the corresponding Docetaxel Teva vial. 
 
Remove the syringe and needle and mix manually by repeated inversions for at least 45 seconds. Do 
not shake. 
 
Allow the premix vial to stand for 5 minutes at room temperature (below 25°C) and then check that 
the solution is homogenous and clear (foaming is normal even after 5 minutes due to the presence of 
polysorbate 80 in the formulation). 
 
The premix solution contains 10 mg/ml docetaxel and should be used immediately after preparation. 
However the chemical and physical stability of the premix solution has been demonstrated for 8 hours 
when stored either between 2°C and 8°C or at room temperature (below 25°C). 



79 

 
b) Preparation of the infusion solution 

More than one premix vial may be necessary to obtain the required dose for the patient. Based on the 
required dose for the patient expressed in mg, aseptically withdraw the corresponding premix volume 
containing 10 mg/ml docetaxel from the appropriate number of premix vials using graduated syringes 
fitted with a needle. For example, a dose of 140 mg docetaxel would require 14 ml docetaxel premix 
solution. 
 
Inject the required premix volume into a non-PVC 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 200 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 Docetaxel Teva infusion solution should be used within 4 hours and should be aseptically 
administered as a 1-hour infusion under room temperature (below 25°C) and normal lighting 
conditions. 
 
As with all parenteral products, Docetaxel Teva premix solution and infusion solution should be 
visually inspected prior to use, solutions containing a precipitate should be discarded. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 

 
 

7. MARKETING AUTHORISATION HOLDER 

Teva B.V. 
Swensweg 5 
2031 GA Haarlem 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER 
 
EU/1/09/611/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 26 January 2010 
Date of latest renewal: 22 May 2014 
 
 
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   



80 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

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 



81 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Pharmachemie BV. 
Swensweg 5, Postbus 552, 2003 RN Haarlem 
The Netherlands 
 
TEVA Pharmaceutical Works Private Limited Company 
H-2100 Gödöllő, Táncsics Mihály út 82 
Hungary 
 
 
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 
 
The marketing authorisation holder shall submit periodic safety update reports for this product in 
accordance with the requirements set out in the list of Union reference dates (EURD list) provided for 
under Article 107c(7) of Directive 2001/83/EC and 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) 
 
Not applicable. 
 
• Obligation to conduct post-authorisation measures 
 
Not applicable 
 
  



82 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 

 
  



83 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



84 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON – 20 mg/0.72 ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Docetaxel Teva 20 mg/0.72 ml concentrate and solvent for solution for infusion 
docetaxel 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial of Docetaxel Teva 20 mg/0.72 ml concentrate contains 20 mg docetaxel. Each ml of 
concentrate contains 27.73 mg docetaxel. 
 
 
3. LIST OF EXCIPIENTS 
 
Docetaxel concentrate vial: 
polysorbate 80, anhydrous ethanol (see leaflet for further information). 
 
Solvent vial: 
water for injections. 
 

 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate and solvent for solution for infusion. 
Each carton contains: 
• one vial of 0.72 ml concentrate (20 mg of docetaxel), 
• one vial of 1.28 ml solvent (water for injections). 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intravenous use.  
CAUTION: Dilution of concentrate required using the entire contents of the solvent vial. 
Reconstituted solution must be further diluted in the infusion diluent before administration. 
Read the package leaflet before use. 
 
 
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. To be administered under the supervision of a physician experienced in the use of 
cytotoxic agents. 
 
 
8. EXPIRY DATE 



85 

 
EXP 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
Do not freeze. 
 
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 
 
Single-use vials. 
Discard unused contents appropriately. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Teva B.V. 
Swensweg 5 
2031 GA Haarlem 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/611/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
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 
 



86 

PC: {number} 
SN: {number} 
NN: {number] 
  



87 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL – CONCENTRATE 20 mg/0.72 ml 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Docetaxel Teva 20 mg/0.72 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 
 
0.72 ml (Fill: 0.88 ml) 
 
 
6. OTHER 
 
 
  



88 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL – SOLVENT FOR 20 mg/0.72 ml 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Solvent for Docetaxel Teva 20 mg/0.72 ml 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
water for injections 
1.28 ml (Fill: 1.71 ml) 
 
 
6. OTHER 
 
 
 
  



89 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON – 80 mg/2.88 ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Docetaxel Teva 80 mg/2.88 ml concentrate and solvent for solution for infusion 
docetaxel 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial of Docetaxel Teva 80 mg/2.88 ml concentrate contains 80 mg docetaxel. Each ml of 
concentrate contains 27.73 mg docetaxel. 
 
 
3. LIST OF EXCIPIENTS 
 
Docetaxel concentrate vial: 
polysorbate 80, anhydrous ethanol (see leaflet for further information). 
 
Solvent vial: 
water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate and solvent for solution for infusion. 
Each carton contains: 
• one vial (2.88 ml) of concentrate (80 mg of docetaxel), 
• one vial (5.12 ml) of solvent (water for injections). 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intravenous use.  
CAUTION: Dilution of concentrate required using the entire contents of the solvent vial. 
Reconstituted solution must be further diluted in the infusion diluent before administration. 
  
Read the package leaflet before use. 
 
 
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. To be administered under the supervision of a physician experienced in the use of 
cytotoxic agents. 
 
 



90 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
Do not freeze. 
 
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 

 
Single-use vials. 
Discard unused contents appropriately. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Teva B.V. 
Swensweg 5 
2031 GA Haarlem 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/611/002  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
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. 



91 

 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: {number} 
SN: {number} 
NN: {number] 
  



92 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL – CONCENTRATE 80 mg/2.88 ml 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Docetaxel Teva 80 mg/2.88 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 
 
2.88 ml (Fill: 3.40 ml) 
 
 
6. OTHER 
 
 
  



93 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL – SOLVENT FOR 80 mg/2.88 ml 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Solvent for Docetaxel Teva 80 mg/2.88 ml 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
water for injections 
5.12 ml (Fill: 6.29 ml) 
 
 
6. OTHER 
 
 
  



94 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
  



95 

Package leaflet: Information for the patient 
 

Docetaxel Teva 20 mg/0.72 ml concentrate and solvent 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 Teva is and what it is used for 
2. What you need to know before you use Docetaxel Teva 
3. How to use Docetaxel Teva 
4. Possible side effects 
5. How to store Docetaxel Teva 
6. Contents of the pack and other information 
 
 
1. What Docetaxel Teva is and what it is used for 
 
The name of this medicine is Docetaxel Teva. Docetaxel is a substance derived from the needles of 
yew trees. 
Docetaxel belongs to the group of anti-cancer medicines called taxoids. 
 
Docetaxel Teva 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 Teva 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 

Teva could be administered in combination with doxorubicin and cyclophosphamide. 
- For the treatment of lung cancer, Docetaxel Teva could be administered either alone or in 

combination with cisplatin. 
- For the treatment of prostate cancer, Docetaxel Teva is administered in combination with 

prednisone or prednisolone. 
- For the treatment of metastatic gastric cancer, Docetaxel Teva is administered in combination 

with cisplatin and 5-fluorouracil. 
- For the treatment of head and neck cancer, Docetaxel Teva is administered in combination with 

cisplatin and 5-fluorouracil. 
 
 
2. What you need to know before you use Docetaxel Teva 
 
You must NOT be given Docetaxel Teva: 
• if you are allergic (hypersensitive) to docetaxel or any of the other ingredients of Docetaxel 

Teva (listed in section 6). 
• if the number of white blood cells is too low. 
• if you have a severe liver disease. 
 
Warnings and precautions 
 
Before each treatment with Docetaxel Teva, you will have blood tests to check that you have enough 
blood cells and sufficient liver function to receive Docetaxel Teva. In case of white blood cells 
disturbances, you may experience associated fever or infections.  
 



96 

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 Teva 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 Teva 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. 
 
Docetaxel Teva contains alcohol. Discuss with your doctor if you suffer from alcohol dependency, 
epilepsy or liver impairment. See also section ”Docetaxel Teva contains ethanol (alcohol)” below.  
 
Other medicines and Docetaxel Teva 
 
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 Teva 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 Teva 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 Teva 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 Teva. 
 
If you are a man being treated with Docetaxel Teva 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. 
 



97 

Docetaxel Teva contains ethanol (alcohol) 
 
This medicinal product contains 25.1 % (w/w) ethanol, anhydrous (alcohol), i.e. up to 181 mg ethanol, 
anhydrous per concentrate vial, equivalent to 4.6 ml beer or 1.9 ml wine. 
 
Harmful for those suffering from alcoholism. 
To be taken into account in pregnant or breastfeeding women, children and high-risk groups such as 
patients with liver disease, or epilepsy. 
 
The amount of alcohol in this medicinal product 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 Teva 
 
Docetaxel Teva 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 Teva 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 Teva. 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. 
 
 
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 Teva 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 Teva may be increased when Docetaxel Teva 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 



98 

• 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 Teva 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 
• 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. 
 
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). 



99 

 
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, potassium, magnesium, and/or calcium 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. 
 
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 Teva 
 
Keep this medicine out of the sight and reach of children. 
 
This medicine should not be used after the expiry date which is stated on the carton and vials after 
“EXP”. The expiry date refers to the last day of that month.  
 
Do not store above 25°C. 
Do not freeze. 
 
Store in the original package in order to protect from light. 
 
The premix solution should be used immediately after preparation. However the chemical and physical 
stability of the premix solution has been demonstrated for 8 hours when stored either between 2°C and 
8°C or at room temperature (below 25°C). 
 
The infusion solution should be used within 4 hours at room temperature (below 25°C). 
 
Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines 
no longer used. These measures will help to protect the environment. 
 
6. Contents of the pack and other information 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


100 

 
What Docetaxel Teva concentrate vial contains: 
- The active substance is docetaxel. Each vial of Docetaxel Teva 20 mg/0.72 ml concentrate 

contains 20 mg of docetaxel. Each ml of concentrate contains 27.73 mg docetaxel. 
 
- The other ingredients are polysorbate 80 and 25.1% (w/w) anhydrous ethanol (see section 2). 
 
What the solvent vial contains: 
Water for injections. 
 
What Docetaxel Teva looks like and contents of the pack: 
Docetaxel Teva concentrate for solution for infusion is a clear viscous, yellow to brown-yellow 
solution. 
 
Each carton contains: 

• one 6 ml clear glass vial with a flip-off cap containing 0.72 ml concentrate and, 
• one 6 ml clear glass vial with a flip-off cap containing 1.28 ml of solvent.  
 

 
Marketing Authorisation Holder 
Teva B.V. 
Swensweg 5 
2031 GA Haarlem 
The Netherlands 
 
Manufacturer: 
Pharmachemie B.V. 
Swensweg 5 
PO Box 552 
2003 RN  Haarlem  
The Netherlands 
 
TEVA Pharmaceutical Works Private Limited Company 
Táncsics Mihály út 82 
H-2100 Gödöllő,  
Hungary 
 
 
For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder: 
 

België/Belgique/Belgien  
Teva Pharma Belgium N.V./S.A./AG  
Tel/Tél: +32 3 820 73 73 
 

Lietuva 
UAB “Sicor Biotech” 
Tel: +370 5 266 02 03 
 

България  
Актавис ЕАД 
Teл.: +359 2 489 95 85 
 

Luxembourg/Luxemburg  
Teva Pharma Belgium N.V./S.A./AG  
Tél: +32 3 820 73 73 
 

Česká republika  
Teva Pharmaceuticals CR, s.r.o.  
Tel: +420 251 007 111  
 

Magyarország  
Teva Gyógyszergyár Zrt.  
Tel.: +36 1 288 64 00 
 

Danmark  
Teva Denmark A/S  
Tlf: +45 44 98 55 11  
 

Malta  
Teva Pharmaceuticals Ireland 
Τel: +353 51 321 740 
 



101 

Deutschland 
Teva GmbH 
Tel: +49 731 402 08 
 

Nederland  
Teva Nederland B.V. 
Tel: +31 800 0228 400 
 

Eesti 
Teva Eesti esindus UAB Sicor Biotech 
Eesti filiaal 
Tel: +372 661 0801 
 

Norge 
Teva Norway AS 
Tlf: +47 66 77 55 90 
 

Ελλάδα 
Teva Ελλάς Α.Ε. 
Τηλ: +30 211 880 5000 

Österreich 
ratiopharm Arzneimittel Vertriebs-GmbH 
Tel: +43 1 97007 0 
 

España 
Teva Pharma, S.L.U. 
Tél: +34 91 387 32 80 
 

Polska 
Teva Pharmaceuticals Polska Sp. z o.o. 
Tel.: +48 22 345 93 00 
 

France 
Teva Santé 
Tél: +33 1 55 91 78 00 
 

Portugal 
Teva Pharma - Produtos Farmacêuticos Lda 
Tel: +351 21 476 75 50 
 

Hrvatska 
Pliva Hrvatska d.o.o 
Tel: + 385 1 37 20 000 
 

România 
Teva Pharmaceuticals S.R.L 
Tel: +40 21 230 65 24 
 

Ireland 
Teva Pharmaceuticals Ireland 
Tel: +353 51 321 740 
 

Slovenija 
Pliva Ljubljana d.o.o. 
Tel: +386 1 58 90 390 
 

Ísland 
ratiopharm Oy 
Sími: +358 20 180 5900 
 

Slovenská republika 
Teva Pharmaceuticals Slovakia s.r.o. 
Tel: +421 2 5726 7911 
 

Italia 
Teva Italia S.r.l. 
Tel: +39 0289 17981 
 

Suomi/Finland 
ratiopharm Oy 
Puh/Tel: +358 20 180 5900 
 

Κύπρος 
Teva Ελλάς Α.Ε. 
Τηλ: +30 211 880 5000 

Sverige 
Teva Sweden AB 
Tel: +46 42 12 11 00 
 

Latvija 
UAB Sicor Biotech filiāle Latvijā  
Tel: +371 67 323 666 
 

United Kingdom 
Teva UK Limited 
Tel: +44 1977 628 500 
 

 
 
This leaflet was last revised in {MM/YYYY}. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site 
http://www.ema.europa.eu/. 

http://www.ema.europa.eu/


102 

The following information is intended for healthcare professionals only: 

PREPARATION GUIDE FOR USE WITH DOCETAXEL TEVA 20 mg/0.72 ml 
CONCENTRATE AND SOLVENT FOR SOLUTION FOR INFUSION  
__________________________________________________________________________ 

It is important that you read the entire contents of this guide prior to the preparation of either the 
Docetaxel Teva premix solution or the Docetaxel Teva infusion solution 
 
 
1. FORMULATION 

Docetaxel Teva 20 mg/0.72 ml concentrate for solution for infusion is a clear viscous, yellow to 
brown-yellow solution containing 27.73 mg/ml docetaxel in polysorbate 80. The solvent for Docetaxel 
Teva is water for injections. 
 
 
2. PRESENTATION 

Docetaxel Teva is supplied as single-dose vials. 
 
Each box contains one Docetaxel Teva vial (20 mg/0.72 ml) and one corresponding solvent for 
Docetaxel Teva vial in a carton. 
 
Docetaxel Teva vials should not be stored above 25°C and should be protected from light. 
Docetaxel Teva should not be used after the expiry date shown on the carton and vials. 
 
2.1 Docetaxel Teva 20 mg/0.72 ml vial: 

• The Docetaxel Teva 20 mg/0.72 ml vial is a 6 ml clear glass vial with a bromobutyl rubber 
stopper and a flip-off cap. 

 
• The Docetaxel Teva 20 mg/0.72 ml vial contains a solution of docetaxel in polysorbate 80 at a 

concentration of 27.73 mg/ml. 
 
• Each vial contains 20 mg/0.72 ml of a 27.73 mg/ml solution of docetaxel in polysorbate 80 (fill 

volume: 24.4 mg/0.88 ml). This volume has been established during the development of 
docetaxel to compensate for liquid loss during preparation of the premix (see section 4) due to 
foaming, adhesion to the walls of the vial and "dead-volume". This overfill ensures that after 
dilution with the entire contents of the accompanying solvent for docetaxel vial, there is a 
minimal extractable premix volume of 2 ml containing 10 mg/ml docetaxel which corresponds 
to the labelled amount of 20 mg/0.72 ml per vial. 

 
2.2 Solvent for Docetaxel Teva 20 mg/0.72 ml  vial: 

• The solvent for Docetaxel Teva 20 mg/0.72 ml vial is a 6 ml clear glass vial with a bromobutyl 
rubber stopper and a flip-off cap. 

 
• The solvent for Docetaxel Teva composition is water for injections. 
 
• Each solvent vial contains 1.28 ml of water for injections (fill volume: 1.71 ml). The addition of 

the entire contents of the solvent vial to the contents of the Docetaxel Teva 20 mg/0.72 ml 
concentrate for solution for infusion vial ensures a premix concentration of 10 mg/ml docetaxel. 

 
 
3. RECOMMENDATIONS FOR THE SAFE HANDLING 
 



103 

Docetaxel Teva is an antineoplastic agent and, as with other potentially toxic compounds, caution 
should be exercised when handling it and preparing Docetaxel Teva solutions. The use of gloves is 
recommended. 
 
If Docetaxel Teva concentrate, premix solution or infusion solution should come into contact with 
skin, wash immediately and thoroughly with soap and water. If Docetaxel Teva concentrate, premix 
solution or infusion solution should come into contact with mucous membranes, wash immediately 
and thoroughly with water. 
 
 
4. PREPARATION FOR THE INTRAVENOUS ADMINISTRATION 

4.1 Preparation of the Docetaxel Teva premix solution (10 mg docetaxel/ml) 
 
4.1.1  If the vials are stored under refrigeration, allow the required number of Docetaxel Teva boxes 
to stand at room temperature (below 25°C) for 5 minutes. 
 
4.1.2  Using a syringe fitted with a needle, aseptically withdraw the entire contents of the solvent for 

Docetaxel Teva vial by partially inverting the vial. 
 

4.1.3 Inject the entire contents of the syringe into the corresponding Docetaxel Teva vial. 
 
4.1.4  Remove the syringe and needle and mix manually by repeated inversions for at least 45 

seconds. Do not shake. 
 
4.1.4 Allow the premix vial to stand for 5 minutes at room temperature (below 25°C) and then 

check that the solution is homogenous and clear (foaming is normal even after 5 minutes due 
to the presence of polysorbate 80 in the formulation). 
 
The premix solution contains 10 mg/ml docetaxel and should be used immediately after 
preparation. However the chemical and physical stability of the premix solution has been 
demonstrated for 8 hours when stored either between +2°C and +8°C or at room temperature 
(below 25°C). 

 
 
 
4.2 Preparation of the infusion solution 
 
4.2.1  More than one premix vial may be necessary to obtain the required dose for the patient. Based 

on the required dose for the patient expressed in mg, aseptically withdraw the corresponding 
premix volume containing 10 mg/ml docetaxel from the appropriate number of premix vials 
using graduated syringes fitted with a needle. For example, a dose of 140 mg docetaxel would 
require 14 ml docetaxel premix solution. 

 
4.2.2 Inject the required premix volume into a 250 ml non-PVC 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 200 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. 

 
4.2.3 Mix the infusion bag or bottle manually using a rocking motion. 
 
4.2.4  The Docetaxel Teva infusion solution should be used within 4 hours and should be aseptically 

administered as a 1-hour infusion under room temperature (below 25°C) and normal lighting 
conditions. 

 
4.2.5 As with all parenteral products, Docetaxel Teva premix solution and infusion solution should 

be visually inspected prior to use, solutions containing a precipitate should be discarded. 



104 

 
 
 
5. 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. 



105 

Package leaflet: Information for the patient 
 

Docetaxel Teva 80 mg/2.88 ml concentrate and solvent 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 Teva is and what it is used for 
2. What you need to know before you use Docetaxel Teva 
3. How to use Docetaxel Teva 
4. Possible side effects 
5. How to store Docetaxel Teva 
6. Contents of the pack and other information 
 
 
1. What Docetaxel Teva is and what it is used for 
 
The name of this medicine is Docetaxel Teva. Docetaxel is a substance derived from the needles of 
yew trees. 
Docetaxel belongs to the group of anti-cancer medicines called taxoids. 
 
Docetaxel Teva 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 Teva 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 

Teva could be administered in combination with doxorubicin and cyclophosphamide. 
- For the treatment of lung cancer, Docetaxel Teva could be administered either alone or in 

combination with cisplatin. 
- For the treatment of prostate cancer, Docetaxel Teva is administered in combination with 

prednisone or prednisolone. 
- For the treatment of metastatic gastric cancer, Docetaxel Teva is administered in combination 

with cisplatin and 5-fluorouracil. 
- For the treatment of head and neck cancer, Docetaxel Teva is administered in combination with 

cisplatin and 5-fluorouracil. 
 
 
2. What you need to know before you use Docetaxel Teva 
 
You must NOT be given Docetaxel Teva: 
• if you are allergic (hypersensitive) to docetaxel or any of the other ingredients of Docetaxel 

Teva (listed in section 6). 
• if the number of white blood cells is too low. 
• if you have a severe liver disease. 
 
Warnings and precautions 
 



106 

Before each treatment with Docetaxel Teva, you will have blood tests to check that you have enough 
blood cells and sufficient liver function to receive Docetaxel Teva. 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 Teva 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 Teva 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. 
 
Docetaxel Teva contains alcohol. Discuss with your doctor if you suffer from alcohol dependency, 
epilepsy or liver impairment. See also section “Docetaxel Teva contains ethanol (alcohol)” below. 
 
Other medicines and Docetaxel Teva 
 
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 Teva 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 Teva 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 Teva 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 Teva. 
 
If you are a man being treated with Docetaxel Teva 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. 



107 

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 Teva contains ethanol (alcohol) 
 
This medicinal product contains 25.1 % (w/w) ethanol, anhydrous (alcohol), i.e. up to 723 mg ethanol, 
anhydrous per concentrate vial, equivalent to 18.3 ml beer or 7.6 ml wine. 
 
Harmful for those suffering from alcoholism. 
To be taken into account in pregnant or breastfeeding women, children and high-risk groups such as 
patients with liver disease, or epilepsy. 
 
The amount of alcohol in this medicinal product 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 Teva 
 
Docetaxel Teva 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 Teva 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 Teva. 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. 
 
 
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 Teva 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 Teva may be increased when Docetaxel Teva is given in 
combination with other chemotherapeutic agents. 
 



108 

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 Teva 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 
• 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. 
 
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 



109 

• dry mouth 
• difficulty or painful swallowing 
• haemorrhage 
• raised liver enzymes (hence the need for regular blood tests). 
 
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, potassium, magnesium, and/or calcium 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.  
 
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 Teva 
 
Keep this medicine out of the sight and reach of children. 
 
This medicine should not be used after the expiry date which is stated on the carton and vials after 
“EXP”. The expiry date refers to the last day of that month.  
 
Do not store above 25°C. 
Do not freeze. 
 
Store in the original package in order to protect from light. 
 
The premix solution should be used immediately after preparation. However the chemical and physical 
stability of the premix solution has been demonstrated for 8 hours when stored either between 2°C and 
8°C or at room temperature (below 25°C). 
 
The infusion solution should be used within 4 hours at room temperature (below 25°C). 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


110 

 
Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines 
no longer used. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Docetaxel Teva concentrate vial contains: 
- The active substance is docetaxel. Each vial of Docetaxel Teva 80 mg/2.88 ml concentrate 

contains 80 mg of docetaxel.  Each ml of concentrate contains 27.73 mg docetaxel. 
 
- The other ingredients are polysorbate 80 and 25.1% (w/w) anhydrous ethanol (see section 2). 
 
What the solvent vial contains: 
Water for injections. 
 
What Docetaxel Teva looks like and contents of the pack: 
Docetaxel Teva concentrate for solution for infusion is a clear viscous, yellow to brown-yellow 
solution. 
 
Each carton contains: 

• one 15 ml clear glass vial with a flip-off cap containing 2.88 ml concentrate and, 
• one 15 ml clear glass vial with a flip-off cap containing 5.12 ml of solvent.  

 
 
Marketing Authorisation Holder 
Teva B.V. 
Swensweg 5 
2031 GA Haarlem 
The Netherlands 
 
Manufacturer: 
Pharmachemie B.V. 
Swensweg 5 
PO Box 552 
2003 RN  Haarlem 
The Netherlands 
 
TEVA Pharmaceutical Works Private Limited Company 
Táncsics Mihály út 82 
H-2100 Gödöllő,  
Hungary 
 
 
 
For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder: 
 

België/Belgique/Belgien  
Teva Pharma Belgium N.V./S.A./AG  
Tel/Tél: +32 3 820 73 73 
 

Lietuva 
UAB “Sicor Biotech” 
Tel: +370 5 266 02 03 
 

България  
Актавис ЕАД 
Teл.: +359 2 489 95 85 
 

Luxembourg/Luxemburg  
Teva Pharma Belgium N.V./S.A./AG  
Tél: +32 3 820 73 73 
 



111 

Česká republika  
Teva Pharmaceuticals CR, s.r.o.  
Tel: +420 251 007 111  
 

Magyarország  
Teva Gyógyszergyár Zrt.  
Tel.: +36 1 288 64 00 
 

Danmark  
Teva Denmark A/S  
Tlf: +45 44 98 55 11  
 

Malta  
Teva Pharmaceuticals Ireland 
Τel: +353 51 321 740 
 

Deutschland 
Teva GmbH 
Tel: +49 731 402 08 
 

Nederland  
Teva Nederland B.V. 
Tel: +31 800 0228 400 
 

Eesti 
Teva Eesti esindus UAB Sicor Biotech 
Eesti filiaal 
Tel: +372 661 0801 
 

Norge 
Teva Norway AS 
Tlf: +47 66 77 55 90 
 

Ελλάδα 
Teva Ελλάς Α.Ε. 
Τηλ: +30 211 880 5000 
 

Österreich 
ratiopharm Arzneimittel Vertriebs-GmbH 
Tel: +43 1 97007 0 
 

España 
Teva Pharma, S.L.U. 
Tél: +34 91 387 32 80 
 

Polska 
Teva Pharmaceuticals Polska Sp. z o.o. 
Tel.: +48 22 345 93 00 
 

France 
Teva Santé 
Tél: +33 1 55 91 78 00 
 

Portugal 
Teva Pharma - Produtos Farmacêuticos Lda 
Tel: +351 21 476 75 50 
 

Hrvatska 
Pliva Hrvatska d.o.o 
Tel: + 385 1 37 20 000 
 

România 
Teva Pharmaceuticals S.R.L 
Tel: +40 21 230 65 24 
 

Ireland 
Teva Pharmaceuticals Ireland 
Tel: +353 51 321 740 
 

Slovenija 
Pliva Ljubljana d.o.o. 
Tel: +386 1 58 90 390 
 

Ísland 
ratiopharm Oy 
Sími: +358 20 180 5900 
 

Slovenská republika 
Teva Pharmaceuticals Slovakia s.r.o. 
Tel: +421 2 5726 7911 
 

Italia 
Teva Italia S.r.l. 
Tel: +39 0289 17981 
 

Suomi/Finland 
ratiopharm Oy 
Puh/Tel: +358 20 180 5900 
 

Κύπρος 
Teva Ελλάς Α.Ε. 
Τηλ: +30 211 880 5000 

Sverige 
Teva Sweden AB 
Tel: +46 42 12 11 00 
 

Latvija 
UAB Sicor Biotech filiāle Latvijā  
Tel: +371 67 323 666 
 

United Kingdom 
Teva UK Limited 
Tel: +44 1977 628 500 
 

 
This leaflet was last revised in {MM/YYYY} 
 
Other sources of information 



112 

 
Detailed information on this medicine is available on the European Medicines Agency web site 
http://www.ema.europa.eu/. 

http://www.emea.eurpa.eu/


113 

The following information is intended for healthcare professionals only: 

PREPARATION GUIDE FOR USE WITH DOCETAXEL TEVA 80 mg/2.88 ml 
CONCENTRATE AND SOLVENT FOR SOLUTION FOR INFUSION  
__________________________________________________________________________ 

It is important that you read the entire contents of this guide prior to the preparation of either the 
Docetaxel Teva premix solution or the Docetaxel Teva infusion solution 
 
 
1. FORMULATION 

Docetaxel Teva 80 mg/2.88 ml concentrate for solution for infusion is a clear viscous, yellow to 
brown-yellow solution containing 27.73 mg/ml docetaxel in polysorbate 80. The solvent for Docetaxel 
Teva is water for injections. 
 
 
2. PRESENTATION 

Docetaxel Teva is supplied as single-dose vials. 
 
Each box contains one Docetaxel Teva vial (80 mg/2.88 ml) and one corresponding solvent for 
Docetaxel Teva vial in a carton. 
 
Docetaxel Teva vials should not be stored above 25°C and should be protected from light. 
Docetaxel Teva should not be used after the expiry date shown on the carton and vials. 
 
 
2.1 Docetaxel Teva 80 mg/2.88 ml vial: 

• The Docetaxel Teva 80 mg/2.88 ml vial is a 15 ml clear glass vial with a bromobutyl rubber 
stopper and a flip-off cap. 

 
• The Docetaxel Teva 80 mg/2.88 ml vial contains a solution of docetaxel in polysorbate 80 at a 

concentration of 27.73 mg/ml. 
 

Each vial contains 80 mg/2.88 ml of a 27.73 mg/ml solution of docetaxel in polysorbate 80 (fill 
volume: 94.4 mg/3.40 ml). This volume has been established during the development of 
docetaxel to compensate for liquid loss during preparation of the premix (see section 4) due to 
foaming, adhesion to the walls of the vial and "dead-volume". This overfill ensures that after 
dilution with the entire contents of the accompanying solvent for docetaxel vial, there is a 
minimal extractable premix volume of 8 ml containing 10 mg/ml docetaxel which corresponds 
to the labelled amount of 80 mg/2.88 ml per vial. 

 
2.2 Solvent for Docetaxel Teva 80 mg/2.88 ml vial: 

• The solvent for Docetaxel Teva 80 mg/2.88 ml vial is a 15 ml clear glass vial with a bromobutyl 
rubber stopper and a flip-off cap. 

 
• The solvent for Docetaxel Teva composition is water for injections. 
 

Each solvent vial contains 5.12 ml of water for injections (fill volume: 6.29 ml). The addition of 
the entire contents of the solvent vial to the contents of the Docetaxel Teva 80 mg/2.88 ml 
concentrate for solution for infusion vial ensures a premix concentration of 10 mg/ml docetaxel. 

 
 
3. RECOMMENDATIONS FOR THE SAFE HANDLING 
 



114 

Docetaxel Teva is an antineoplastic agent and, as with other potentially toxic compounds, caution 
should be exercised when handling it and preparing Docetaxel Teva solutions. The use of gloves is 
recommended. 
 
If Docetaxel Teva concentrate, premix solution or infusion solution should come into contact with 
skin, wash immediately and thoroughly with soap and water. If Docetaxel Teva concentrate, premix 
solution or infusion solution should come into contact with mucous membranes, wash immediately 
and thoroughly with water. 
 
 
4. PREPARATION FOR THE INTRAVENOUS ADMINISTRATION 

4.1 Preparation of the Docetaxel Teva premix solution (10 mg docetaxel/ml) 
 
4.1.1 If the vials are stored under refrigeration, allow the required number of Docetaxel Teva boxes 

to stand at room temperature (below 25°C) for 5 minutes. 
 

4.1.2 Using a syringe fitted with a needle, aseptically withdraw the entire contents of the solvent for 
Docetaxel Teva vial by partially inverting the vial. 
 

4.1.3 Inject the entire contents of the syringe into the corresponding Docetaxel Teva vial. 
 
4.1.4 Remove the syringe and needle and mix manually by repeated inversions for at least 45 

seconds. Do not shake. 
 
4.1.5 Allow the premix vial to stand for 5 minutes at room temperature (below 25°C) and then 

check that the solution is homogenous and clear (foaming is normal even after 5 minutes due 
to the presence of polysorbate 80 in the formulation). 
 
The premix solution contains 10 mg/ml docetaxel and should be used immediately after 
preparation. However the chemical and physical stability of the premix solution has been 
demonstrated for 8 hours when stored either between +2°C and +8°C or at room temperature 
(below 25°C). 

 
 
 
4.2 Preparation of the infusion solution 
 
4.2.1 More than one premix vial may be necessary to obtain the required dose for the patient. Based 

on the required dose for the patient expressed in mg, aseptically withdraw the corresponding 
premix volume containing 10 mg/ml docetaxel from the appropriate number of premix vials 
using graduated syringes fitted with a needle. For example, a dose of 140 mg docetaxel would 
require 14 ml docetaxel premix solution. 

 
4.2.2 Inject the required premix volume into a 250 ml non-PVC 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 200 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. 

 
4.2.3 Mix the infusion bag or bottle manually using a rocking motion. 
 
4.2.4  The Docetaxel Teva infusion solution should be used within 4 hours and should be aseptically 

administered as a 1-hour infusion under room temperature (below 25°C) and normal lighting 
conditions. 

 
4.2.5 As with all parenteral products, Docetaxel Teva premix solution and infusion solution should 

be visually inspected prior to use, solutions containing a precipitate should be discarded. 
 



115 

 
 
5. 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