Docefrez

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Docefrez 20 mg powder and solvent for concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each single-dose vial of powder contains 20 mg docetaxel (anhydrous).  
After reconstitution, 1 ml of concentrate contains 24 mg docetaxel.  
 
Excipients: the solvent contains 35.4% (w/w) ethanol. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for concentrate for solution for infusion. 
 
White lyophilised powder. 
The solvent is a viscous, clear and colourless solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 

 
Breast cancer 

Docetaxel 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 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 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 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 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 

Docetaxel is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung 
cancer after failure of prior chemotherapy. 



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Docetaxel 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 in combination with prednisone or prednisolone is indicated for the treatment of patients with 
hormone refractory metastatic prostate cancer.  
 

 
Gastric adenocarcinoma 

Docetaxel 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 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). 
 

 
Recommended dose 

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). Prophylactic G-CSF may be 
used to mitigate the risk of haematological toxicities. 
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). 
 
Docetaxel is administered as a one-hour infusion every three weeks.  
 

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). 

Breast cancer 

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. 
 
In combination with capecitabine, the recommended dose of docetaxel is 75 mg/m2 every three weeks, 
combined with capecitabine at 1250 mg/m2 twice daily (within 30 minutes after a meal) for 2 weeks 



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followed by a 1-week rest period. For capecitabine dose calculation according to body surface area, see 
capecitabine summary of product characteristics. 
 

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. 

Non-small cell lung 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). 

Prostate cancer 

 

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. 

Gastric adenocarcinoma 

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). 
 

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. 

Head and neck cancer 

 
• 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 

Docetaxel should be administered when the neutrophil count is ≥1,500 cells/mm3. In patients who 
experienced either febrile neutropenia, neutrophil count <500 cells/mm3 for more than one week, severe or 
cumulative cutaneous reactions or severe peripheral neuropathy during docetaxel therapy, the dose of 
docetaxel should be reduced from 100 mg/m2 to 75 mg/m2 and/or from 75 to 60 mg/m2. If the patient 
continues to experience these reactions at 60 mg/m2, the treatment should be discontinued. 

General 

 
Adjuvant therapy for breast cancer 



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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. 
 

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 cisplatin 

 

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

• 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. 
 

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). 

In combination with cisplatin and 5-fluorouracil 

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. 
 
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 (e.g. day 6-15) in all subsequent cycles. 
 

 
Special populations: 



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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. 

Patients with hepatic impairment 

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. 
 

The safety and efficacy of docetaxel in nasopharyngeal carcinoma in children aged 1 month to less than 18 
years have not yet been established. 

Paediatric population 

There is no relevant use of docetaxel 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. 
 

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). 

Elderly 

 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients. 
 
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 

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). 
 



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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). 
 

 
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. 
 

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). 

Cutaneous reactions 

 

 
Fluid retention 

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

 
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. 
 

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

 

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



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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). 

Cardiac toxicity 

 
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. 
 

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). 

Others 

 
Additional cautions for use in adjuvant treatment of breast cancer 

For patients who experience complicated neutropenia (prolonged neutropenia, febrile neutropenia or 
infection), G-CSF and dose reduction should be considered (see section 4.2). 

Complicated neutropenia 

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. 

Gastrointestinal reactions 

Patients should be monitored for symptoms of congestive heart failure during therapy and during the follow 
up period. 

Congestive heart failure 

In the docetaxel, doxorubicin and cyclophosphamide (TAC) treated patients, the risk of delayed 
myelodysplasia or myeloid leukaemia requires haematological follow-up. 

Leukaemia 

The benefit/risk ratio for TAC in patients with 4+ nodes was not defined fully at the interim analysis (see 
section 5.1). 

Patients with 4+ nodes 

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

Elderly 

 
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 the elderly patients compared to younger patients. The incidence of the following 
adverse events (all grades): lethargy, stomatitis, neutropenic infection occurred at rates ≥ 10% higher in 
patients who were 65 years of age or older compared to younger patients. 
Elderly patients treated with TCF should be closely monitored. 
 

This medicinal product contains small amounts of ethanol (alcohol), less than 100 mg per dose. 
Ethanol 

 
4.5 Interaction with other medicinal products and other forms of interaction 
 



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In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant 
administration of compounds which induce, inhibit or are metabolised by (and thus may inhibit the enzyme 
competitively) cytochrome P450-3A such as ciclosporine, terfenadine, ketoconazole, erythromycin and 
troleandomycin. 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. 
 
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. 
 
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 should be administered with caution in patients concomitantly receiving potent CYP3A4 
inhibitors (e.g. protease inhibitors like ritonavir, azole antifungals like ketoconazole or itraconazole). A drug 
interaction study performed in patients receiving ketoconazole and docetaxel showed that the clearance of 
docetaxel was reduced by half by ketoconazole, probably because the metabolism of docetaxel involves 
CYP3A4 as a major (single) metabolic pathway. Reduced tolerance of docetaxel may occur, even at lower 
doses. 
 
4.6 Pregnancy and lactation 
 
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 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 potential /contraception: 

Women of childbearing age receiving docetaxel should be advised to avoid becoming pregnant, and to 
inform the treating physician immediately should this occur. 
 
An effective method of contraception should be used during treatment. 
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. 
 

 
Lactation: 

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. 
 
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. 
 



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4.8 Undesirable effects 
 
The adverse reactions considered to be possibly or probably related to the administration of docetaxel have 
been obtained in: 
• 1312 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). 
• 1276 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) and the COSTART terms and the MedDRA terms. Frequencies are defined as: very common 
(≥ 1/10), common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); 
very rare (< 1/10,000); not known (cannot be estimated from 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: 
 

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. 

Immune system disorders 

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 paresthesia, dysesthesia or pain including 
burning. Neuro-motor events are mainly characterised by weakness. 
 



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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). 
 

 
Docetaxel 100 mg/m² single agent 

MedDRA system 
organ classes 
 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions  

Infections and 
infestations 

Infections (G3/4;5.7%; 
including sepsis and 
pneumonia, fatal in 
1.7%) 

Infection associated with 
G4 neutropenia 
(G3/4:4.6%) 

 

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%) 



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

 

 

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

Nervous system 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. 

Skin and subcutaneous tissue disorders 

 

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. 

General disorders and administration site conditions 

 

 
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) 



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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%) 

 

 
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 G3/4 AST increased 



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increased (<2.5%); 
G3/4 Blood alkaline 
phosphatase increased 
(<2.5%) 

(<1%); 
G3/4 ALT increased 
(<1%) 

 

 
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%) 

 

 
Docetaxel 100 mg/m² in combination with trastuzumab: 

MedDRA system organ 
classes 

Very common adverse 
reactions 

Common adverse 
reactions 



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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 Paresthesia; 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  
 

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. 

Cardiac 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). 

Blood and lymphatic system disorders 

 

 
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 Anorexia (G3/4: 1%); Dehydration (G3/4: 2%); 



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

Paraesthesia (G3/4: <1%) 
Dizziness; 
Headache (G3/4: <1%); 
Neuropathy peripheral 

Eye disorders Lacrimation increased  
Respiratory, thoracic and 
mediastinal disorders 

Pharyngolaryngeal pain 
(G3/4: 2%) 

Dyspnoea (G3/4: 1%); 
Cough (G3/4: <1%); 
Epistaxis (G3/4: <1%) 

Gastrointestinal disorders Stomatitis (G3/4: 18%); 
Diarrhoea (G3/4: 14%); 
Nausea (G3/4: 6%); 
Vomiting (G3/4: 4%); 
Constipation (G3/4: 1%); 
Abdominal pain (G3/4: 2%); 
Dyspepsia 

Abdominal pain upper; 
Dry mouth 

Skin and subcutaneous tissue 
disorders 

Hand-foot syndrome (G3/4: 
24%) 
Alopecia (G3/4: 6%); 
Nail disorders (G3/4: 2%) 

Dermatitis; 
Rash erythematous (G3/4: 
<1%);  
Nail discolouration; 
Onycholysis (G3/4: 1%) 

Musculoskeletal and connective 
tissue disorders 

Myalgia (G3/4: 2%); 
Arthralgia (G3/4: 1%) 

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

General disorders and 
administration site conditions 

Asthenia (G3/4: 3%); 
Pyrexia (G3/4: 1%); 
Fatigue/weakness (G3/4: 5%); 
Oedema peripheral (G3/4: 1%) 

Lethargy; 
Pain 

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

 

 
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%) 

 



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Skin and subcutaneous tissue 
disorders 

Alopecia; 
Nail disorders (no severe) 

Exfoliative rash (G3/4: 0.3%) 

Musculoskeletal and connective 
bone disorders 

 Arthralgia (G3/4: 0.3%); 
Myalgia (G3/4: 0.3%) 

General disorders and 
administration site conditions 

Fatigue (G3/4: 3.9%); 
Fluid retention (severe 0.6%) 

 

 
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 2.7%). 
 

  

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 (G3/4: 
<0.1%); 
Skin disorder (G3/4: 
0.6%); 
Nail disorders (G3/4: 
0.4%) 

  



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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%) 

 

 
 

Peripheral sensory neuropathy was observed to be ongoing during follow-up in 12 patients out of the 83 
patients with peripheral sensory neuropathy at the end of the chemotherapy. 

Nervous system disorders 

 

Congestive Heart Failure (CHF) has been reported in 18 of 1276 patiens during the follow-up period. 
Cardiac disorders 

In the node positive study (TAX316) one patient in each treatment arm died because of cardiac failure. 
 

Alopecia was observed to be ongoing during follow-up in 25 patients out of the 736 patients with alopecia at 
the end of the chemotherapy. 

Skin and subcutaneous tissue disorders 

 

Amenorrhoea was observed to be ongoing during follow-up in 140 patients out of the 251 patients with 
amenorrhoea at the end of the chemotherapy. 

Reproductive system and breast disorders 

 

Peripheral oedema was observed to be ongoing during follow-up time in 18 patients out of the 112 patients 
with peripheral oedema at the end of the chemotherapy in study TAX 316, whereas lymphoedema was 
observed to be ongoing in 4 of the 5 patients with lymphoedema at the end of the chemotherapy in the study 
GEICAM 9805. 

General disorders and administration site conditions 

 

At a median follow-up time of 77 months, acute leukaemia occurred in 1 of 532 (0.2%) patients who 
received docetaxel, doxorubicin, and cyclophosphamide in the GEICAM 9805 study. No cases were 
reported in patients who received fluorouracil, doxorubicin and cyclophosphamide. No patient was 
diagnosed with myelodysplastic syndrome in either treatment groups. 

Acute leukaemia / Myelodysplastic syndrome 

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) 



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Neutropenic infection 
(Grade 3-4) 

2 (1.8) 5 (1.2) 

 

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

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/odynop 
hagia (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%). 

 

 

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). 

Blood and lymphatic system disorders 

 

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

• 
 

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 

 Cancer pain (G3/4: 
0.6%) 

 



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(incl cysts and 
polyps) 
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 

 Cancer pain (G3/4: 
1.2%) 

 



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(incl cysts and 
polyps) 
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 

Very rare cases of acute myeloid leukaemia and myelodysplastic syndrome have been reported in 
association with docetaxel when used in combination with other chemotherapy agents and/or radiotherapy. 

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



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Bone marrow suppression and other haematologic adverse reactions have been reported. Disseminated 
intravascular coagulation (DIC), often in association with sepsis or multiorgan failure, has been reported. 

Blood and lymphatic system disorders 

 

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

Nervous system 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. 

Eye disorders 

 

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

 

Rare cases of myocardial infarction have been reported. 
Cardiac disorders 

 

Venous thromboembolic events have rarely been reported. 
Vascular disorders 

 

Acute respiratory distress syndrome, interstitial pneumonia and pulmonary fibrosis have rarely been 
reported. Rare cases of radiation pneumonitis have been reported in patients receiving concomitant 
radiotherapy. 

Respiratory, thoracic and mediastinal disorders 

 

Rare occurrences of dehydration as a consequence of gastrointestinal events, gastrointestinal perforation, 
colitis ischaemic, colitis and neutropenic enterocolitis have been reported. Rare cases of ileus and intestinal 
obstruction have been reported.  

Gastrointestinal disorders 

 

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

Hepatobiliary 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. Sclerodermal-like changes 
usually preceded by peripheral lymphoedema have been reported with docetaxel. 

Skin and subcutaneous tissue disorders 

 

Radiation recall phenomena have rarely been reported.  
General disorders and administration site conditions 

Fluid retention has not been accompanied by acute episodes of oliguria or hypotension. Dehydration and 
pulmonary oedema have rarely been reported. 
 
 
4.9 Overdose 
 



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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: L01CD02 
 

 
Preclinical data 

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. 
 
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 antitumour activity against 
advanced murine and human grafted tumours. 
 

 
Clinical data 

 
Breast cancer 

Docetaxel in combination with doxorubicin and cyclophosphamide: adjuvant therapy 
 
Patients with operable node-positive breast cancer
Data from a multicenter open label randomized study support the use of docetaxel for the adjuvant treatment 
of patients with operable node-positive breast cancer and KPS ≥ 80%, between 18 and 70 years of age. After 
stratification according to the number of positive lymph nodes (1-3, 4+), 1491 patients were randomized to 
receive either docetaxel 75 mg/m2 administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 
500 mg/m2 (TAC arm), or doxorubicin 50 mg/m2 followed by fluorouracil 500 mg/m2 and 
cyclosphosphamide 500 mg/m2 (FAC arm). Both regimens were administered once every 3 weeks for 6 
cycles. Docetaxel was administered as a 1-hour infusion, all other medicinal products were given as 
intravenous bolus on day one. G-CSF was administered as secondary prophylaxis to patients who 
experienced complicated neutropenia (febrile neutropenia, prolonged neutropenia, or infection). Patients on 
the TAC arm received antibiotic prophylaxis with ciprofloxacin 500 mg orally twice daily for 10 days 
starting on day 5 of each cycle, or equivalent. In both arms, after the last cycle of chemotherapy, patients 
with positive estrogen 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. 

 (TAX 316) 

An interim analysis was performed with a median follow up of 55 months. Significantly longer disease-free 
survival for the TAC arm compared to the FAC arm was demonstrated. Incidence of relapses at 5 years was 
reduced in patients receiving TAC compared to those who received FAC (25% versus 32%, respectively) 
i.e. an absolute risk reduction by 7% (p=0.001). Overall survival at 5 years was also significantly increased 
with TAC compared to FAC (87% versus 81%, respectively) i.e. an absolute reduction of the risk of death 



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by 6% (p=0.008). TAC-treated patient subsets according to prospectively defined major prognostic factors 
were analyzed: 
 
 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 

 
 

0.72 

 
 

0.59-0.88 

 
 

0.001 

 
 

0.70 

 
 

0.53-0.91 

 
 

0.008 
1-3 467 0.61 0.46-0.82 0.0009 0.45 0.29-0.70 0.0002 
4+ 278 0.83 0.63-1.08 0.17 0.94 0.66-1.33 0.72 
*a hazard ratio of less than 1 indicates that TAC is associated with a longer disease-free survival and overall 
survival compared to FAC 
 
The beneficial effect of TAC was not proven in patients with 4 and more positive nodes (37% of the 
population) at the interim analysis stage. The effect appears to be less pronounced than in patients with 1-3 
positive nodes. The benefit/risk ratio was not defined fully in patients with 4 and more positive nodes at this 
analysis stage. 
 
Patients with operable node-negative breast cancer eligible to receive chemotherapy
 

 (GEICAM 9805) 

Data from a multicenter open label randomized trial support the use of docetaxel for the adjuvant treatment 
of patients with operable node-negative breast cancer eligible to receive chemotherapy. 1060 patients were 
randomized 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 drugs were given intravenously on day 1 every three weeks. Primary prophylactic 
G-CSF was made mandatory in TAC arm after 230 patients were randomized. 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. 
 
Median duration of follow-up was 77 months. Significantly longer disease-free survival for the TAC arm 
compared to the FAC arm was demonstrated. TAC-treated patients had a 32% reduction in the risk of 
relapse compared to those treated with FAC (hazard ratio = 0.68, 95% CI (0.49-0.93), p = 0.01). Overall 
survival (OS) was also longer in the TAC arm with TAC-treated patients having a 24% reduction in the risk 
of death compared to FAC (hazard ratio = 0.76, 95% CI (0.46-1.26, p = 0.29). However, the distribution of 
OS was not significantly different between the 2 groups.  
 
TAC-treated patient subsets according to prospectively defined major prognostic factors were analyzed (see 
table below): 
 
Subset Analyses-Adjuvant Therapy in Patients with Node-negative Breast Cancer Study 

 
(Intent-to-Treat Analysis) 

        Disease Free Survival 
Patient subset Number of patients 

in TAC group 
Hazard ratio* 95% CI 

Overall 539 0.68 0.49-0.93 



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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 
 

 
 

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 = estrogen receptor 
PR = progesterone receptor 
aER/PR-negative or Grade 3 or tumor 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 



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progression (docetaxel 27 weeks vs. doxorubicin 23 weeks, p=0.54), docetaxel increased response rate (52% 
vs. 37%, p=0.01) and shortened time to response (12 weeks vs. 23 weeks, p=0.007). Three docetaxel 
patients (2%) discontinued the treatment due to fluid retention, whereas 15 doxorubicin patients (9%) 
discontinued due to cardiac toxicity (three cases of fatal congestive heart failure). 
 
In anthracycline-failure patients, docetaxel was compared to the combination of mitomycin C and 
vinblastine (12 mg/m² every 6 weeks and 6 mg/m² every 3 weeks). Docetaxel increased response rate (33% 
vs. 12%, p<0.0001), prolonged time to progression (19 weeks vs. 11 weeks, p=0.0004) and prolonged 
overall survival (11 months vs. 9 months, p=0.01). 
 
During these two phase III studies, the safety profile of docetaxel was consistent with the safety profile 
observed in phase II studies (see section 4.8).  
 
An open-label, multicenter, randomized 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 randomized 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 randomized 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 randomized 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 



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(FISH). In this study, 87% of patients had disease that was IHC 3+, and 95% of patients entered had disease 
that was IHC 3+ and/or FISH positive. Efficacy results are summarized in the following table. 
 
Parameter Docetaxel plus trastuzumab1 

n=92 
Docetaxel1 

n=94 
Response rate  
(95% CI) 

61%  
(50-71) 

34% 
(25-45) 

Median duration of response 
(months) 
(95% CI) 

 
11.4  

(9.2 – 15.0) 

 
5.1  

(4.4 – 6.2) 
Median TTP (months) 
(95% CI) 

10.6  
(7.6 – 12.9) 

5.7 
(5.0-6.5) 

Median survival (months) 
(95% CI) 

30.52 
(26.8-ne) 

22.12 
(17.6-28.9) 

TTP=time to progression; “ne” indicates that it could not be estimated or it was not yet reached. 
1Full analysis set (intent-to-treat) 
2 Estimated median survival 
 
Docetaxel in combination with capecitabine 
 
Data from one multicenter, randomised, controlled phase III clinical study support the use of docetaxel in 
combination with capecitabine for treatment of patients with locally advanced or metastatic breast cancer 
after failure of cytotoxic chemotherapy, including an anthracycline. In this study, 255 patients were 
randomised to treatment with docetaxel (75 mg/m2 as a 1 hour intravenous infusion every 3 weeks) and 
capecitabine (1250 mg/m2 twice daily for 2 weeks followed by 1-week rest period). 256 patients were 
randomised to treatment with docetaxel alone (100 mg/ m2 as a 1 hour intravenous infusion every 3 weeks). 
Survival was superior in the docetaxel +capecitabine combination arm (p=0.0126). Median survival was 
442 days (docetaxel + capecitabine) vs. 352 days (docetaxel alone). 
The overall objective response rates in the all-randomised population (investigator assessment) were 41.6% 
(docetaxel + capecitabine) vs. 29.7% (docetaxel alone); p = 0.0058. Time to progressive disease was 
superior in the docetaxel + capecitabine combination arm (p<0.0001). The median time to progression was 
186 days (docetaxel + capecitabine) vs. 128 days (docetaxel alone). 
 

 
Non-small cell lung cancer 

Patients previously treated with chemotherapy with or without radiotherapy 
 
In a phase III study, in previously treated patients, time to progression (12.3 weeks versus 7 weeks) and 
overall survival were significantly longer for docetaxel at 75 mg/m² compared to Best Supportive Care. The 
1-year survival rate was also significantly longer in docetaxel (40%) versus BSC (16%). There was less use 
of morphinic analgesic (p<0.01), non-morphinic analgesics (p<0.01), other disease-related 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, 1218 patients with unresectable stage IIIB or IV NSCLC, with KPS of 70% or greater, 
and who did not receive previous chemotherapy for this condition, were randomised to either Docetaxel (T) 
75 mg/m2 as a 1 hour infusion immediately followed by cisplatin (Cis) 75 mg/ m2 over 30-60 minutes every 
3 weeks (TCis), docetaxel 75 mg/ m2 as a 1 hour infusion in combination with carboplatin (AUC 
6 mg/ml.min) over 30-60 minutes every 3 weeks, or vinorelbine (V) 25 mg/ m2 administered over 6-10 
minutes on days 1, 8, 15, 22 followed by cisplatin 100 mg/m2 administered on day 1 of cycles repeated 
every 4 weeks (VCis). 



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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 endpoint) 

   

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] 

Medium 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 randomized multicenter phase III study. A 
total of 1006 patients with KPS≥60 were randomized 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 (%) 

291 
45.4 

282 
47.9 

300 
31.7 



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95% CI 
p-value* 

(39.5-51.3) 
0.0005 

(41.9-53.9) 
<0.0001 

(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 multicenter, open-label, randomized study was conducted to evaluate the safety and efficacy of docetaxel 
for the treatment of patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the 
gastroesophageal junction, who had not received prior chemotherapy for metastatic disease. A total of 445 
patients with KPS>70 were treated with either docetaxel (T) (75 mg/m2 on day 1) in combination with 
cisplatin (C) (75 mg/m2 on day 1) and 5-fluorouracil (F) (750 mg/m2 per day for 5 days) or cisplatin 
(100 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2 per day for 5 days). The length of a treatment cycle 
was 3 weeks for the TCF arm and 4 weeks for the CF arm. The median number of cycles administered per 
patient was 6 (with a range of 1-16) for the TCF arm compared to 4 (with a range of 1-12) for the CF arm. 
Time to progression (TTP) was the primary endpoint. The risk reduction of progression was 32.1% and was 
associated with a significantly longer TTP (p=0.0004) in favor of the TCF arm. Overall survival was also 
significantly longer (p=0.0201) in favor 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) 9.2 8.6 
(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 logrank test 



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Subgroup analyses across age, gender and race consistently favored 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 favor 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, multicenter, open-label, randomized study 
(TAX323). In this study, 358 patients with inoperable locally advanced SCCHN, and WHO perfomance 
status 0 or 1, were randomized to one of two treatment arms. Patients on the docetaxel arm received 
docetaxel 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 favor 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: 
 



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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 progression free survival (months) 
(95%CI) 

18.6 
(15.7-24.0) 

14.5 
(11.6-18.7) 

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

0.72 
(0.56-0.93) 

0.0128 
Best overall response to chemotherapy (%) 
(95%CI) 
***p-value 

67.8 
(60.4-74.6) 

53.6 
(46.0-61.0) 

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

72.3 
(65.1-78.8) 

58.6 
(51.0-65.8) 

0.006 

Median duration of response to chemotherapy ± 
radiotherapy (months) 
(95%CI) 

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 favors Docetaxel +Cisplatin+5-FU 
*Cox model (adjustment for Primary tumour site, T and N clinical stages and PSWHO) 
**Logrank test 
*** Chi-square test 
 
Quality of life parameters 
Patients treated with TPF experienced significantly less deterioration of their Global health score compared 
to those treated with PF (p=0.01, using the EORTC QLQ-C30 scale). 
 
Clinical benefit parameters 
The performance status scale, for head and neck (PSS-HN) subscales designed to measure understandability 
of speech, ability to eat in public, and normalcy of diet, was significantly in favor 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. 
 



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• 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 randomized, multicenter 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 randomized to one of two arms. The study population comprised patients 
with technically unresectable disease, patients with low probability of surgical cure and patients aiming at 
organ preservation. The efficacy and safety evaluation solely addressed survival endpoints and the success 
of organ preservation was not formally addressed. Patients on the docetaxel arm received docetaxel (T) 
75 mg/m² by intravenous infusion on day 1 followed by cisplatin (P) 100 mg/m² administered as a 30-minute 
to three-hour intravenous infusion, followed by the continuous intravenous infusion of 5-fluorouracil (F) 
1000 mg/m²/day from day 1 to day 4. The cycles were repeated every 3 weeks for 3 cycles. All patients who 
did not have progressive disease were to receive chemoradiotherapy (CRT) as per protocol (TPF/CRT).  
Patients on the comparator arm received cisplatin (P) 100 mg/m² as a 30-minute to three-hour intravenous 
infusion on day 1 followed by the continuous intravenous infusion of 5-fluorouracil (F) 1000 mg/m²/day 
from day 1 to day 5.  The cycles were repeated every 3 weeks for 3 cycles. All patients who did not have 
progressive disease were to receive CRT as per protocol (PF/CRT).   
Patients in both treatment arms were to receive 7 weeks of CRT following induction chemotherapy with a 
minimum interval of 3 weeks and no later than 8 weeks after start of the last cycle (day 22 to day 56 of last 
cycle). During radiotherapy, carboplatin (AUC 1.5) was given weekly as a one-hour intravenous infusion for 
a maximum of 7 doses.  Radiation was delivered with megavoltage equipment using once daily fractionation 
(2 Gy per day, 5 days per week for 7 weeks, for a total dose of 70-72 Gy). Surgery on the primary site of 
disease and/or neck could be considered at anytime following completion of CRT. All patients on the 
docetaxel-containing arm of the study received prophylactic antibiotics. The primary efficacy endpoint in 
this study, overall survival (OS) was significantly longer (log-rank test, p = 0.0058) with the docetaxel-
containing regimen compared to PF (median OS: 70.6 versus 30.1 months respectively), with a 30% risk 
reduction in mortality compared to PF (hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.54-0.90) 
with an overall median follow up time of 41.9 months. The secondary endpoint, PFS, demonstrated a 29% 
risk reduction of progression or death and a 22 month improvement in median PFS (35.5 months for TPF 
and 13.1 for PF). This was also statistically significant with an HR of 0.71; 95% CI 0.56-0.90; log-rank test 
p = 0.004.  
Efficacy results are presented in the table below: 



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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 favors 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 
 
5.2 Pharmacokinetic properties 
 
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. 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. 
 
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. 
 
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. 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 



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lowered by 27% on average (see section 4.2). 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. 
 
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.  
 
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.  
 
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. 
 
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. 
 
The effect of prednisone on the pharmacokinetics of docetaxel administered with standard dexamethasone 
premedication has been studied in 42 patients. 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 
 

Ethanol, anhydrous 
Solvent 

Polysorbate 80 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in section 
6.6. 

Do not use any PVC equipment or device. Docefrez is incompatible with PVC equipment or devices. 
 
6.3 Shelf life 
 

24 months 
Vial 

 



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The reconstituted solution contains 24 mg/ml docetaxel and should be used immediately after preparation.  
Reconstituted solution 

 
Chemical and physical in-use stability of the reconstituted solution has been demonstrated for 8 hours when 
stored either between 2°C and 8°C or below 25°C and for the final solution for infusion for 4 hours below 
25°C . 
From a microbiological point of view, the reconstituted solution 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 hrs at 2 to 8°C, unless reconstitution and further dilution has taken place in 
controlled and validated aseptic conditions. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Keep the vial in the outer carton in order to protect from light. 
 
For storage conditions of the reconstituted and diluted medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 

 
Docefrez 20 mg powder and solvent for concentrate for solution for infusion 

5 ml colourless type 1 glass vial with grey bromobutyl rubber stopper and sealed with a dark green colour 
flip-off aluminium seal. 

Powder vial: 

 
Solvent vial
1 ml colourless type 1 glass vial with grey bromobutyl rubber stopper sealed with dark blue flip-off with 
aluminium seal. 

: 

 
Each carton contains: 
• one single-dose  powder vial with 20 mg docetaxel (plus 22% overfill: 24.4 mg), and 
• one single-dose solvent vial with 1 ml solvent for Docefrez 
 
The overfills are included to ensure that, after dilution with the entire volume of the accompanying solvent 
vial, the minimum extractable volume of reconstituted concentrate containing 20 mg or 80 mg docetaxel, 
respectively, may be withdrawn from the vial. 
 
6.6 Special precautions for disposal and other handling 
 
Docetaxel is an antineosplastic agent and, as with other potentially cytotoxic compounds, caution should be 
exercised when preparing docetaxel solutions. An appropriate aseptic technique should be used for all steps.  
 
If docetaxel powder, reconstituted concentrate or solution for infusion should come into contact with skin, 
wash immediately and thoroughly with soap and water. If docetaxel powder, reconstituted concentrate, or 
solution for infusion should come into contact with mucous membranes, wash immediately and thoroughly 
with water. 
 
Both the reconstituted concentrate and the solution for infusion should be visually inspected prior to use. 
Any solution containing a precipitate should be discarded. 

Do not use any PVC equipment or device. Docefrez is incompatible with PVC equipment or devices. 

Docefrez powder and solvent for concentrate for solution for infusion is for single use only. 
 



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Instructions for reconstitution
More than one vial may be necessary to obtain the required dose for the patient. For example, a dose of 
140 mg docetaxel would require one 80 mg pack and three 20 mg packs. The required number of Docefrez 
powder vials should be allowed to reach room temperature (between 15°C  - 25°C) for 5 minutes. 

  

Using a syringe with a needle, the entire contents of the correct vial of solvent for Docefrez is to be 
withdrawn and injected into the respective Docefrez powder vials.  
Shake well for complete solubilisation of powder (the powder will be dissolved in less than 90 seconds).  
The reconstituted solution contains approximately 24 mg/ml docetaxel and should be used immediately after 
preparation.  
 

After reconstitution, each vial contains an extractable volume of approx 0.84 ml concentrate, corresponding 
to approximately 20 mg docetaxel.  

Preparation of the infusion solution 

 
The volume of concentrate (24 mg/ml docetaxel) corresponding to the required dose (mg) for the patient 
should be withdrawn (from the appropriate number of vials) using graduated syringes fitted with a needle.  
 
This volume of concentrate should be injected into a 250 ml infusion bag or bottle containing either glucose 
50 mg/ml (5%) solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. 
 
If a dose greater than 200 mg docetaxel is required, a larger volume of the infusion vehicle should be used, 
so that a concentration of 0.74 mg/ml docetaxel is not exceeded in the final solution for infusion. 
 
The solution in the infusion bag or bottle should be allowed to mix manually using a rocking motion. 
 

The docetaxel infusion solution should be used within 4 hours and should be aseptically administered as a 
1 hour infusion under room temperature and normal lighting conditions. 

Method of administration  

 

Any unused product or waste material should be disposed of in accordance with local requirements. 
Disposal 

 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel: +31-23-5685501 
fax: +31-23-5685505 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/630/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 10 May 2010 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 



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Detailed information on this product is available on the website of the European Medicines Agency (EMA): 
http://www.ema.europa.eu. 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Docefrez 80 mg powder and solvent for concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each single-dose vial of powder contains 80 mg docetaxel (anhydrous). 
After reconstitution, 1 ml of concentrate contains 24 mg docetaxel.  
 
Excipients: the solvent contains 35.4% (w/w) ethanol. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for concentrate for solution for infusion. 
 
White lyophilised powder. 
The solvent is a viscous, clear and colourless solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 

 
Breast cancer 

Docetaxel 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 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 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 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 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 

Docetaxel is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung 
cancer after failure of prior chemotherapy. 



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Docetaxel 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 in combination with prednisone or prednisolone is indicated for the treatment of patients with 
hormone refractory metastatic prostate cancer.  
 

 
Gastric adenocarcinoma 

Docetaxel 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 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). 
 

 
Recommended dose 

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). Prophylactic G-CSF may be 
used to mitigate the risk of haematological toxicities. 
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). 
 
Docetaxel is administered as a one-hour infusion every three weeks.  

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). 

Breast cancer 

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. 
 
In combination with capecitabine, the recommended dose of docetaxel is 75 mg/m2 every three weeks, 
combined with capecitabine at 1250 mg/m2 twice daily (within 30 minutes after a meal) for 2 weeks 
followed by a 1-week rest period. For capecitabine dose calculation according to body surface area, see 
capecitabine summary of product characteristics. 



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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. 

Non-small cell lung 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). 

Prostate cancer 

 

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. 

Gastric adenocarcinoma 

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). 
 

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. 

Head and neck cancer 

 
• 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 

Docetaxel should be administered when the neutrophil count is ≥1,500 cells/mm3. In patients who 
experienced either febrile neutropenia, neutrophil count <500 cells/mm3 for more than one week, severe or 
cumulative cutaneous reactions or severe peripheral neuropathy during docetaxel therapy, the dose of 
docetaxel should be reduced from 100 mg/ m2 to 75 mg/m2 and/or from 75 to 60 mg/ m2. If the patient 
continues to experience these reactions at 60 mg/m2, the treatment should be discontinued. 

General 

 

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/m2in all subsequent cycles 

Adjuvant therapy for breast cancer 



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(see sections 4.4 and 4.8). Patients who experience Grade 3 or 4 stomatitis should have their dose decreased 
to 60 mg/m2. 
 

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 cisplatin 

 

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

• 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. 
 

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). 

In combination with cisplatin and 5-fluorouracil 

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. 
 
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 (e.g. day 6-15) in all subsequent cycles. 
 

 
Special populations: 

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 

Patients with hepatic impairment 



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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. 
 

The safety and efficacy of docetaxel in nasopharyngeal carcinoma in children aged 1 month to less than 18 
years have not yet been established. 

Paediatric population 

There is no relevant use of docetaxel 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. 
 

Based on a population pharmacokinetic analysis, there are no special instructions for use in the elderly. 
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). 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients. 
 
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 

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 



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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). 
 

 
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. 
 

 
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. 
 

 
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). 



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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. 
 

 
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). 
 
Additional cautions for use in adjuvant treatment of breast cancer 

For patients who experience complicated neutropenia (prolonged neutropenia, febrile neutropenia or 
infection), G-CSF and dose reduction should be considered (see section 4.2). 

Complicated neutropenia 

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. 

Gastrointestinal reactions 

Patients should be monitored for symptoms of congestive heart failure during therapy and during the follow 
up period. 

Congestive heart failure 

In the docetaxel, doxorubicin and cyclophosphamide (TAC) treated patients, the risk of delayed 
myelodysplasia or myeloid leukaemia requires haematological follow-up. 

Leukaemia 

The benefit/risk ratio for TAC in patients with 4+ nodes was not defined fully at the interim analysis (see 
section 5.1). 

Patients with 4+ nodes 

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

Elderly 

 
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 the elderly patients compared to younger patients. The incidence of the following 
adverse events (all grades): lethargy, stomatitis, neutropenic infection occurred at rates ≥ 10% higher in 
patients who were 65 years of age or older compared to younger patients. 
Elderly patients treated with TCF should be closely monitored. 
 

This medicinal product contains small amounts of ethanol (alcohol), less than 100 mg per dose. 
Ethanol 

 
4.5 Interaction with other medicinal products and other forms of interaction 



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In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant 
administration of compounds which induce, inhibit or are metabolised by (and thus may inhibit the enzyme 
competitively) cytochrome P450-3A such as ciclosporine, terfenadine, ketoconazole, erythromycin and 
troleandomycin. 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. 
 
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. 
 
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 should be administered with caution in patients concomitantly receiving potent CYP3A4 
inhibitors (e.g. protease inhibitors like ritonavir, azole antifungals like ketoconazole or itraconazole). A drug 
interaction study performed in patients receiving ketoconazole and docetaxel showed that the clearance of 
docetaxel was reduced by half by ketoconazole, probably because the metabolism of docetaxel involves 
CYP3A4 as a major (single) metabolic pathway. Reduced tolerance of docetaxel may occur, even at lower 
doses. 
 
4.6 Pregnancy and lactation 
 
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 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 potential /contraception: 

Women of childbearing age receiving docetaxel should be advised to avoid becoming pregnant, and to 
inform the treating physician immediately should this occur. 
 
An effective method of contraception should be used during treatment. 
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. 
 

 
Lactation: 

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. 
 
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. 



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4.8 Undesirable effects 
 
The adverse reactions considered to be possibly or probably related to the administration of docetaxel have 
been obtained in: 
• 1312 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). 
• 1276 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; grade3-4 = G3/4; 
grade 4 = G4) and the COSTART terms and the MedDRA terms. Frequencies are defined as: very common 
(≥ 1/10), common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); 
very rare (< 1/10,000); not known (cannot be estimated from 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 



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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 paresthesia, 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). 
 
 

 
Docetaxel 100 mg/m² single agent 

MedDRA system 
organ classes 
 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions  

Infections and 
infestations 

Infection (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  Arrythmia (G3/4:0.7%) Cardiac failure 
Vascular disorders  Hypotension; 

Hypertension; 
Haemorrhage 

 

Respiratory, thoracic 
and mediastinal 
disorders 

Dyspnoea (severe 2.7%) 
 

  

Gastrointestinal Stomatitis (G3/4: 5.3%); Constipation (severe Oesophagitis (severe: 



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disorders Diarrhoea (G3/4: 4%); 
Nausea (G3/4: 4%); 
Vomiting (G3/4: 3%) 

0.2%); 
Abdominal pain (severe 
1%); 
Gastrointestinal 
haemorrhage (severe 
0.3%) 

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

 

 

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

Nervous system 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. 

Skin and subcutaneous tissue disorders 

 

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. 

General disorders and administration site conditions 

 

 
Docetaxel 75 mg/m² single agent 

MedDRA system organ classes Very common adverse reactions 
 

Common adverse reactions 
 

Infections and infestations Infection (G3/4: 5%)  
Blood and lymphatic system 
disorders 

Neutropenia (G4: 54.2%); 
Anaemia (G3/4: 10.8%); 
Thrombocytopenia (G4: 1.7%) 

Febrile neutropenia 
 



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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%) 

 

 
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 

 Myalgia  



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disorders 
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%) 

 

 
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 



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(0.3%) 
 

 
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 Paresthesia; 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  
 

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. 

Cardiac disorders 

 

Very common: Haematological toxicity was increased in patients receiving trastuzumab and docetaxel, 
compared with docetaxel alone (32% grade ¾ neutropenia versus 22%, using NCI-CTC criteria). Note that 
this is likely to be an underestimate since docetaxel alone at a dose of 100mg/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). 

Blood and lymphatic system disorders 

 

 
Docetaxel 75 mg/m² in combination with capecitabine 



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MedDRA system organ classes Very common adverse reactions 
 

Common adverse reactions 
 

Infections and infestations  Oral candidiasis (G3/4: <1%) 
Blood and lymphatic system 
disorders 

Neutropenia (G3/4: 63%); 
Anaemia (G3/4: 10%) 

Thrombocytopenia (G3/4: 3%) 

Metabolism and nutrition 
disorders 

Anorexia (G3/4: 1%); 
Decreased appetite 

Dehydration (G3/4: 2%); 

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

Dizziness; 
Headache (G3/4: <1%); 
Neuropathy peripheral 

Eye disorders Lacrimation increased  
Respiratory, thoracic and 
mediastinal disorders 

Pharyngolaryngeal pain 
(G3/4: 2%) 

Dyspnoea (G3/4: 1%); 
Cough (G3/4: <1%); 
Epistaxis (G3/4: <1%) 

Gastrointestinal disorders Stomatitis (G3/4: 18%); 
Diarrhoea (G3/4: 14%); 
Nausea (G3/4: 6%); 
Vomiting (G3/4: 4%); 
Constipation (G3/4: 1%); 
Abdominal pain (G3/4: 2%); 
Dyspepsia 

Abdominal pain upper; 
Dry mouth 

Skin and subcutaneous tissue 
disorders 

Hand-foot syndrome (G3/4: 
24%) 
Alopecia (G3/4: 6%); 
Nail disorders (G3/4: 2%) 

Dermatitis; 
Rash erythematous (G3/4: 
<1%);  
Nail discolouration; 
Onycholysis (G3/4: 1%) 

Musculoskeletal and connective 
tissue disorders 

Myalgia (G3/4: 2%); 
Arthralgia (G3/4: 1%) 

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

General disorders and 
administration site conditions 

Asthenia (G3/4: 3%); 
Pyrexia (G3/4: 1%); 
Fatigue/weakness (G3/4: 5%); 
Oedema peripheral (G3/4: 1%) 

Lethargy; 
Pain 

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

 

 
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%); 



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Cough (G3/4: 0%) 
Gastrointestinal disorders Nausea (G3/4: 2.4%); 

Diarrhoea (G3/4: 1.2%); 
Stomatitis/Pharyngitis (G3/4: 
0.9%); 
Vomiting (G3/4: 1.2%) 

 

Skin and subcutaneous tissue 
disorders 

Alopecia; 
Nail disorders (no severe) 

Exfoliative rash (G3/4: 0.3%) 

Musculoskeletal and connective 
bone disorders 

 Arthralgia (G3/4: 0.3%); 
Myalgia (G3/4: 0.3%) 

General disorders and 
administration site conditions 

Fatigue (G3/4: 3.9%); 
Fluid retention (severe 0.6%) 

 

 
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 2.7%). 
 

  

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%) 

 



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Skin and subcutaneous 
tissue disorders 

Alopecia (G3/4: 
<0.1%); 
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) 

  

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%) 

 

 
 

Peripheral sensory neuropathy was observed to be ongoing during follow-up in 12 patients out of the 83 
patients with peripheral sensory neuropathy at the end of the chemotherapy. 

Nervous system disorders 

 

Congestive Heart Failure (CHF) has been reported in 18 of 1276 patiens during the follow-up period. 
Cardiac disorders 

In the node positive study (TAX316) one patient in each treatment arm died because of cardiac failure. 
 

Alopecia was observed to be ongoing during follow-up in 25 patients out of the 736 patients with alopecia at 
the end of the chemotherapy. 

Skin and subcutaneous tissue disorders 

 

Amenorrhoea was observed to be ongoing during follow-up in 140 patients out of the 251 patients with 
amenorrhoea at the end of the chemotherapy. 

Reproductive system and breast disorders 

 

Peripheral oedema was observed to be ongoing during follow-up time in 18 patients out of the 112 patients 
with peripheral oedema at the end of the chemotherapy in study TAX 316, whereas lymphoedema was 
observed to be ongoing in 4 of the 5 patients with lymphoedema at the end of the chemotherapy in the study 
GEICAM 9805. 

General disorders and administration site conditions 

 

At a median follow-up time of 77 months, acute leukaemia occurred in 1 of 532 (0.2%) patients who 
received docetaxel, doxorubicin, and cyclophosphamide in the GEICAM 9805 study. No cases were 
reported in patients who received fluorouracil, doxorubicin and cyclophosphamide. No patient was 
diagnosed with myelodysplastic syndrome in either treatment groups. 

Acute leukaemia / Myelodysplastic syndrome 

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) 



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 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) 

 

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

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/odynop 
hagia (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%). 

 

 

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). 

Blood and lymphatic system disorders 

 

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

• Induction chemotherapy followed by radiotherapy (TAX 323)
 

. 

MedDRA system Very common adverse Common adverse Uncommon 



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organ classes reactions 
 

reactions 
 

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 Very common Common adverse Uncommon adverse 



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organ classes adverse reactions 
 

reactions 
 

reactions 
 

Infections and 
infestations 

Infection (G3/4: 3.6%) 
 

Neutropenic infection  

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

 Cancer pain (G3/4: 
1.2%) 

 

Blood and lymphatic 
system disorders 

Neutropenia G3/4: 
83.5%) 
Anaemia (G3/4: 
12.4%) 
Thrombocytopenia 
(G3/4: 4.0%); 
Febrile neutropenia 

  

Immune system 
disorders 

  Hypersensitivity 

Metabolism and 
nutrition disorders 

Anorexia (G3/4: 
12.0%) 

  

Nervous system 
disorders 

Dysgeusia/Parosmia 
(G3/4: 0.4%); 
Peripheral sensory 
neuropathy 
(G3/4: 1.2%) 

Dizziness (G3/4: 
2.0%); 
Peripheral motor 
neuropathy 
(G3/4: 0.4%) 

 

Eye disorders  Lacrimation increased Conjunctivitis 
Ear and labyrinth 
disorders 

Hearing impaired 
(G3/4: 1.2%) 

  

Cardiac disorders  Arrhythmia (G3/4: 
2.0%) 

Ischemia myocardial 

Vascular disorders   Venous disorder 
Gastrointestinal 
disorders 

Nausea (G3/4: 13.9%); 
Stomatitis (G3/4: 
20.7%); 
Vomiting (G3/4: 
8.4%); 
Diarrhoea (G3/4: 
6.8%); 
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%) 

  



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Investigations Weight decreased  Weight increased 
 

 
Post-marketing experience 

Very rare cases of acute myeloid leukaemia and myelodysplastic syndrome have been reported in 
association with docetaxel when used in combination with other chemoterapy agents and/or radiotherapy. 

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

 

Bone marrow suppression and other haematologic adverse reactions have been reported. Disseminated 
intravascular coagulation (DIC), often in association with sepsis or multiorgan failure, has been reported. 

Blood and lymphatic system disorders 

 

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

Nervous system 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. 

Eye disorders 

 

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

 

Rare cases of myocardial infarction have been reported. 
Cardiac disorders 

 

Venous thromboembolic events have rarely been reported. 
Vascular disorders 

 

Acute respiratory distress syndrome, interstitial pneumonia and pulmonary fibrosis have rarely been 
reported. Rare cases of radiation pneumonitis have been reported in patients receiving concomitant 
radiotherapy. 

Respiratory, thoracic and mediastinal disorders 

 

Rare occurrences of dehydration as a consequence of gastrointestinal events, gastrointestinal perforation, 
colitis ischaemic, colitis and neutropenic enterocolitis have been reported. Rare cases of ileus and intestinal 
obstruction have been reported.  

Gastrointestinal disorders 

 

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

Hepatobiliary 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. Sclerodermal-like changes 
usually preceded by peripheral lymphoedema have been reported with docetaxel. 

Skin and subcutaneous tissue disorders 

 
General disorders and administration site conditions 



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Radiation recall phenomena have rarely been reported. Fluid retention has not been accompanied by acute 
episodes of oliguria or hypotension. Dehydration and pulmonary oedema have rarely been reported. 
 
 
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: L01CD02 
 

 
Preclinical data 

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. 
 
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 antitumour activity against 
advanced murine and human grafted tumours. 
 

 
Clinical data 

 
Breast cancer 

Docetaxel in combination with doxorubicin and cyclophosphamide: adjuvant therapy 
 
Patients with operable node-positive breast cancer
Data from a multicenter open label randomized study support the use of docetaxel for the adjuvant treatment 
of patients with operable node-positive breast cancer and KPS ≥ 80%, between 18 and 70 years of age. After 
stratification according to the number of positive lymph nodes (1-3, 4+), 1491 patients were randomized to 
receive either docetaxel 75 mg/m2 administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 
500 mg/m2 (TAC arm), or doxorubicin 50 mg/m2 followed by fluorouracil 500 mg/m2 and 
cyclosphosphamide 500  mg/m2 (FAC arm). Both regimens were administered once every 3 weeks for 6 
cycles. Docetaxel was administered as a 1-hour infusion, all other medicinal products were given as 
intravenous bolus on day one. G-CSF was administered as secondary prophylaxis to patients who 
experienced complicated neutropenia (febrile neutropenia, prolonged neutropenia, or infection). Patients on 
the TAC arm received antibiotic prophylaxis with ciprofloxacin 500 mg orally twice daily for 10 days 
starting on day 5 of each cycle, or equivalent. In both arms, after the last cycle of chemotherapy, patients 
with positive estrogen and/or progesterone receptors received tamoxifen 20 mg daily for up to 5 years. 

 (TAX 316) 



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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. 
An interim analysis was performed with a median follow up of 55 months. Significantly longer disease-free 
survival for the TAC arm compared to the FAC arm was demonstrated. Incidence of relapses at 5 years was 
reduced in patients receiving TAC compared to those who received FAC (25% versus 32%, respectively) 
i.e. an absolute risk reduction by 7% (p=0.001). Overall survival at 5 years was also significantly increased 
with TAC compared to FAC (87% versus 81%, respectively) i.e. an absolute reduction of the risk of death 
by 6% (p=0.008). TAC-treated patient subsets according to prospectively defined major prognostic factors 
were analyzed: 
 
 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 

 
 

0.72 

 
 

0.59-0.88 

 
 

0.001 

 
 

0.70 

 
 

0.53-0.91 

 
 

0.008 
1-3 467 0.61 0.46-0.82 0.0009 0.45 0.29-0.70 0.0002 
4+ 278 0.83 0.63-1.08 0.17 0.94 0.66-1.33 0.72 
*a hazard ratio of less than 1 indicates that TAC is associated with a longer disease-free survival and overall 
survival compared to FAC 
 
The beneficial effect of TAC was not proven in patients with 4 and more positive nodes (37% of the 
population) at the interim analysis stage. The effect appears to be less pronounced than in patients with 1-3 
positive nodes. The benefit/risk ratio was not defined fully in patients with 4 and more positive nodes at this 
analysis stage. 
 
Patients with operable node-negative breast cancer eligible to receive chemotherapy
 

 (GEICAM 9805) 

Data from a multicenter open label randomized trial support the use of docetaxel for the adjuvant treatment 
of patients with operable node-negative breast cancer eligible to receive chemotherapy. 1060 patients were 
randomized 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 drugs were given intravenously on day 1 every three weeks. Primary prophylactic 
G-CSF was made mandatory in TAC arm after 230 patients were randomized. 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. 
 
Median duration of follow-up was 77 months. Significantly longer disease-free survival for the TAC arm 
compared to the FAC arm was demonstrated. TAC-treated patients had a 32% reduction in the risk of 
relapse compared to those treated with FAC (hazard ratio = 0.68, 95% CI (0.49-0.93), p = 0.01). Overall 
survival (OS) was also longer in the TAC arm with TAC-treated patients having a 24% reduction in the risk 
of death compared to FAC (hazard ratio = 0.76, 95% CI (0.46-1.26, p = 0.29). However, the distribution of 
OS was not significantly different between the 2 groups.  
 
TAC-treated patient subsets according to prospectively defined major prognostic factors were analyzed (see 
table below): 
 
Subset Analyses-Adjuvant Therapy in Patients with Node-negative Breast Cancer Study 



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(Intent-to-Treat Analysis) 

        
Patient subset 

Disease Free Survival 
Number of patients 

in TAC group 
Hazard ratio* 95% CI 

Overall 539 0.68 0.49-0.93 
Age category 1 
<50 years  
≥50 years 

 
260 
279 

 
0.67 
0.67 

 
0.43-1.05 
0.43-1.05 

Age category 2 
<35 years  
≥35 years 

 
42 

497 

 
0.31 
0.73 

 
0.11-0.89 
0.52-1.01 

Hormonal receptor 
status 
Negative  
Positive 

 
 

195 
344 

 
 

0.7 
0.62 

 
 

0.45-1.1 
0.4-0.97 

Tumour size 
≤2 cm  
>2 cm 

 
285 
254 

 
0.69 
0.68 

 
0.43-1.1 

0.45-1.04 
Histological grade 
Grade1 (includes grade 
not assessed) 
Grade 2  
Grade 3 

 
64 

 
216 
259 

 
0.79 

 
0.77 
0.59 

 
0.24-2.6 

 
0.46-1.3 
0.39-0.9 

Menopausal status 
Pre-Menopausal  
Post-Menopausal 

 
285 
254 

 
0.64 
0.72 

 
0.40-1 

0.47-1.12 
* 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 = estrogen receptor 
PR = progesterone receptor 
aER/PR-negative or Grade 3 or tumor size >5 cm 
 
The estimated hazard ratio was using Cox proportional hazard model with treatment group as the factor. 
 
Docetaxel as single agent 



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Two randomised phase III comparative studies, involving a total of 326 alkylating or 392 anthracycline 
failure metastatic breast cancer patients, have been performed with docetaxel at the recommended dose and 
regimen of 100 mg/m² every 3 weeks. 
 
In alkylating-failure patients, docetaxel was compared to doxorubicin (75 mg/m² every 3 weeks). Without 
affecting overall survival time (docetaxel 15 months vs. doxorubicin 14 months, p=0.38) or time to 
progression (docetaxel 27 weeks vs. doxorubicin 23 weeks, p=0.54), docetaxel increased response rate (52% 
vs. 37%, p=0.01) and shortened time to response (12 weeks vs. 23 weeks, p=0.007). Three docetaxel 
patients (2%) discontinued the treatment due to fluid retention, whereas 15 doxorubicin patients (9%) 
discontinued due to cardiac toxicity (three cases of fatal congestive heart failure). 
 
In anthracycline-failure patients, docetaxel was compared to the combination of mitomycin C and 
vinblastine (12 mg/m² every 6 weeks and 6 mg/m² every 3 weeks). Docetaxel increased response rate (33% 
vs. 12%, p<0.0001), prolonged time to progression (19 weeks vs. 11 weeks, p=0.0004) and prolonged 
overall survival (11 months vs. 9 months, p=0.01). 
 
During these two phase III studies, the safety profile of docetaxel was consistent with the safety profile 
observed in phase II studies (see section 4.8).  
 
An open-label, multicenter, randomized 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 randomized 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 randomized 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 
 



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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 randomized to receive docetaxel (100 mg/m2) with 
or without trastuzumab; 60% of patients received prior anthracycline-based adjuvant chemotherapy. 
Docetaxel plus trastuzumab was efficacious in patients whether or not they had received prior adjuvant 
anthracyclines. The main test method used to determine HER2 positivity in this pivotal study was 
immunohistochemistry (IHC). A minority of patients were tested using fluorescence in-situ hybridization 
(FISH). In this study, 87% of patients had disease that was IHC 3+, and 95% of patients entered had disease 
that was IHC 3+ and/or FISH positive. Efficacy results are summarized in the following table. 
 
Parameter Docetaxel plus trastuzumab1 

n=92 
Docetaxel1 

n=94 
Response rate  
(95% CI) 

61%  
(50-71) 

34% 
(25-45) 

Median duration of response 
(months) 
(95% CI) 

 
11.4  

(9.2 – 15.0) 

 
5.1  

(4.4 – 6.2) 
Median TTP (months) 
(95% CI) 

10.6  
(7.6 – 12.9) 

5.7 
(5.0-6.5) 

Median survival (months) 
(95% CI) 

30.52 
(26.8-ne) 

22.12 
(17.6-28.9) 

TTP=time to progression; “ne” indicates that it could not be estimated or it was not yet reached. 
1Full analysis set (intent-to-treat) 
2 Estimated median survival 
 
Docetaxel in combination with capecitabine 
 
Data from one multicenter, randomised, controlled phase III clinical studysupport the use of docetaxel in 
combination with capecitabine for treatment of patients with locally advanced or metastatic breast cancer 
after failure of cytotoxic chemotherapy, including an anthracycline. In this study, 255 patients were 
randomised to treatment with docetaxel (75 mg/m2 as a 1 hour intravenous infusion every 3 weeks) and 
capecitabine (1250 mg/m2 twice daily for 2 weeks followed by 1-week rest period). 256 patients were 
randomised to treatment with docetaxel alone (100 mg/ m2 as a 1 hour intravenous infusion every 3 weeks). 
Survival was superior in the docetaxel +capecitabine combination arm (p=0.0126). Median survival was 442 
days (docetaxel + capecitabine) vs. 352 days (docetaxel alone). 
The overall objective response rates in the all-randomised population (investigator assessment) were 41.6% 
(docetaxel + capecitabine) vs. 29.7% (docetaxel alone); p = 0.0058. Time to progressive disease was 
superior in the docetaxel + capecitabine combination arm (p<0.0001). The median time to progression was 
186 days (docetaxel + capecitabine) vs. 128 days (docetaxel alone). 
 

 
Non-small Cell Lung Cancer 

Patients previously treated with chemotherapy with or without radiotherapy 
 
In a phase III study, in previously treated patients, time to progression (12.3 weeks versus 7 weeks) and 
overall survival were significantly longer for docetaxel at 75 mg/m² compared to Best Supportive Care. The 
1-year survival rate was also significantly longer in docetaxel (40%) versus BSC (16%). There was less use 
of morphinic analgesic (p<0.01), non-morphinic analgesics (p<0.01), other disease-related 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 
 



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In a phase III study, 1218 patients with unresectable stage IIIB or IV NSCLC, with KPS of 70% or greater, 
and who did not receive previous chemotherapy for this condition, were randomised to either Docetaxel (T) 
75 mg/m2 as a 1 hour infusion immediately followed by cisplatin (Cis) 75 mg/m2 over 30-60 minutes every 
3 weeks (TCis), docetaxel 75 mg/m2 as a 1 hour infusion in combination with carboplatin 
(AUC 6 mg/ml.min) over 30-60 minutes every 3 weeks, or vinorelbine (V) 25 mg/m2 administered over 6-10 
minutes on days 1, 8, 15, 22 followed by cisplatin 100 mg/m2 administered on day 1 of cycles repeated 
every 4 weeks (VCis). 
 
Survival data, median time to progression and response rates for two arms of the study are illustrated in the 
following table. 
 
 TCis 

n=408 
VCis 

n=404 
Statistical analysis 

Overall survival 
(Primary endpoint) 

   

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] 

Medium 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 randomized multicenter phase III study. A 
total of 1006 patients with KPS≥60 were randomized 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 335 334 337 



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Median survival (months) 
95% CI 
Hazard ratio 
95% CI 
p-value†* 

18.9 
(17.0-21.2) 

0.761 
(0.619-0.936) 

0.0094 

17.4 
(15.7-19.0) 

0.912 
(0.747-1.113) 

0.3624 

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 
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 multicenter, open-label, randomized study, was conducted to evaluate the safety and efficacy of docetaxel 
for the treatment of patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the 
gastroesophageal junction, who had not received prior chemotherapy for metastatic disease. A total of 445 
patients with KPS>70 were treated with either docetaxel (T) (75 mg/m2 on day 1) in combination with 
cisplatin (C) (75 mg/m2 on day 1) and 5-fluorouracil (F) (750 mg/m2 per day for 5 days) or cisplatin 
(100 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2 per day for 5 days). The length of a treatment cycle 
was 3 weeks for the TCF arm and 4 weeks for the CF arm. The median number of cycles administered per 
patient was 6 (with a range of 1-16) for the TCF arm compared to 4 (with a range of 1-12) for the CF arm. 
Time to progression (TTP) was the primary endpoint. The risk reduction of progression was 32.1% and was 
associated with a significantly longer TTP (p=0.0004) in favor of the TCF arm. Overall survival was also 
significantly longer (p=0.0201) in favor 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) 9.2 8.6 
(95%CI)  
2-year estimate (%)  
 

9.2 
(8.38-10.58) 

18.4 

8.6 
(7.16-9.46) 

8.8 



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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 logrank test 
 
Subgroup analyses across age, gender and race consistently favored 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 favor 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. 



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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, multicenter, open-label, randomized study 
(TAX323). In this study, 358 patients with inoperable locally advanced SCCHN, and WHO perfomance 
status 0 or 1, were randomized to one of two treatment arms. Patients on the docetaxel arm received 
docetaxel 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 favor 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 

Endpoint 
SCCHN (Intent-to-Treat Analysis) 

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 progression free survival (months) 
(95%CI) 

18.6 
(15.7-24.0) 

14.5 
(11.6-18.7) 

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

0.72 
(0.56-0.93) 

0.0128 
Best overall response to chemotherapy (%) 
(95%CI) 
***p-value 

67.8 
(60.4-74.6) 

53.6 
(46.0-61.0) 

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

72.3 
(65.1-78.8) 

58.6 
(51.0-65.8) 

0.006 

Median duration of response to chemotherapy ± 
radiotherapy (months) 

n=128 
15.7 

n=106 
11.7 



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(95%CI) (13.4-24.6) (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 favors Docetaxel +Cisplatin+5-FU 
*Cox model (adjustment for Primary tumour site, T and N clinical stages and PSWHO) 
**Logrank test 
*** Chi-square test 
 
Quality of life parameters 
Patients treated with TPF experienced significantly less deterioration of their Global health score compared 
to those treated with PF (p=0.01, using the EORTC QLQ-C30 scale). 
 
Clinical benefit parameters 
The performance status scale, for head and neck (PSS-HN) subscales designed to measure understandability 
of speech, ability to eat in public, and normalcy of diet, was significantly in favor 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 randomized, multicenter 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 randomized to one of two arms. The study population comprised patients 
with technically unresectable disease, patients with low probability of surgical cure and patients aiming at 
organ preservation. The efficacy and safety evaluation solely addressed survival endpoints and the success 
of organ preservation was not formally addressed. Patients on the docetaxel arm received docetaxel (T) 
75 mg/m² by intravenous infusion on day 1 followed by cisplatin (P) 100 mg/m² administered as a 30-minute 
to three-hour intravenous infusion, followed by the continuous intravenous infusion of 5-fluorouracil (F) 
1000 mg/m²/day from day 1 to day 4. The cycles were repeated every 3 weeks for 3 cycles. All patients who 
did not have progressive disease were to receive chemoradiotherapy (CRT) as per protocol (TPF/CRT).  
Patients on the comparator arm received cisplatin (P) 100 mg/m² as a 30-minute to three-hour intravenous 
infusion on day 1 followed by the continuous intravenous infusion of 5-fluorouracil (F) 1000 mg/m²/day 
from day 1 to day 5.  The cycles were repeated every 3 weeks for 3 cycles. All patients who did not have 
progressive disease were to receive CRT as per protocol (PF/CRT).   
Patients in both treatment arms were to receive 7 weeks of CRT following induction chemotherapy with a 
minimum interval of 3 weeks and no later than 8 weeks after start of the last cycle (day 22 to day 56 of last 
cycle). During radiotherapy, carboplatin (AUC 1.5) was given weekly as a one-hour intravenous infusion for 
a maximum of 7 doses.  Radiation was delivered with megavoltage equipment using once daily fractionation 
(2 Gy per day, 5 days per week for 7 weeks, for a total dose of 70-72 Gy). Surgery on the primary site of 
disease and/or neck could be considered at anytime following completion of CRT.  All patients on the 
docetaxel-containing arm of the study received prophylactic antibiotics. The primary efficacy endpoint in 
this study, overall survival (OS) was significantly longer (log-rank test, p = 0.0058) with the docetaxel-
containing regimen compared to PF (median OS: 70.6 versus 30.1 months respectively), with a 30% risk 
reduction in mortality compared to PF (hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.54-0.90) 
with an overall median follow up time of 41.9 months. The secondary endpoint, PFS, demonstrated a 29% 
risk reduction of progression or death and a 22 month improvement in median PFS (35.5 months for TPF 
and 13.1 for PF). This was also statistically significant with an HR of 0.71; 95% CI 0.56-0.90; log-rank test 
p = 0.004.  



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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 favors 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 

 
5.2 Pharmacokinetic properties 
 
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. 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. 
 
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. 
 
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. In a small number of 



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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). 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. 
 
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.  
 
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.  
 
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. 
 
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. 
 
The effect of prednisone on the pharmacokinetics of docetaxel administered with standard dexamethasone 
premedication has been studied in 42 patients. 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 
 

Ethanol, anhydrous 
Solvent 

Polysorbate 80 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in section 
6.6. 

Do not use any PVC equipment or device. Docefrez is incompatible with PVC equipment or devices. 
 
6.3 Shelf life 
 

24 months- 
Vial 

 



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Reconstituted solution 
The reconstituted solution contains 24 mg/ml docetaxel and should be used immediately after preparation.  
 
Chemical and physical in-use stability of the reconstituted solution has been demonstrated for 8 hours when 
stored either between 2°C and 8°C or below 25°C and for the final solution for infusion for 4 hours below 
25°C . 
From a microbiological point of view, the reconstituted solution 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 hrs at 2 to 8°C, unless reconstitution and further dilution has taken place in 
controlled and validated aseptic conditions. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Keep the vial in the outer carton in order to protect from light. 
 
For storage conditions of the reconstituted and diluted medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Docefrez 80 mg powder and solvent for concentrate  for solution for infusion 
 

15 ml colourless type 1 glass vial with grey bromobutyl rubber stopper and sealed with a blood red colour 
flip-off aluminium seal 

Powder vial: 

 

5 ml colourless type 1  glass vial with grey bromobutyl rubber stopper sealed with brown colour flip-off 
with aluminium seal. 

Solvent vial: 

 
Each carton contains: 
• one single-dose powder vial with 80 mg docetaxel (plus 18% overfill: 94.4 mg) and 
• one single-dose solvent vial with 4 ml solvent for docefrez (35.4% (w/w) ethanol in polysorbate 80) . 
 
The overfills are included to ensure that, after dilution with the entire volume of the accompanying solvent 
vial, the minimum extractable volume of reconstituted concentrate containing 20 mg or 80 mg docetaxel, 
respectively, may be withdrawn from the vial. 
 
6.6 Special precautions for disposal and other handling 
 
Docetaxel is an antineosplastic agent and, as with other potentially cytotoxic compounds, caution should be 
exercised when preparing docetaxel solutions. An appropriate aseptic technique should be used for all steps.  
 
If docetaxel powder, reconstituted concentrate  or solution for infusion should come into contact with skin, 
wash immediately and thoroughly with soap and water. If docetaxel powder, reconstituted concentrate, or 
solution for infusion should come into contact with mucous membranes, wash immediately and thoroughly 
with water. 
 
Both the reconstituted concentrate and the solution for infusion should be visually inspected prior to use. 
Any solution containing a precipitate should be discarded. 

Do not use any PVC equipment or device. Docefrez is incompatible with PVC equipment or devices. 

Docefrez powder and solvent for concentrate for solution for infusion is for single use only. 
 



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Instructions for reconstitution
 

  

More than one vial may be necessary to obtain the required dose for the patient. For example, a dose of 
140 mg docetaxel would require one 80 mg pack and three 20 mg packs. The required number of Docefrez 
powder vials should be allowed to reach room temperature (between 15°C - 25°C) for 5 minutes. 
Using a syringe with a needle, the entire contents of the correct vial of solvent for Docefrez is to be 
withdrawn and injected into the respective Docefrez powder vials.  
Shake well for complete solubilisation of powder (the powder will be dissolved in less than 90 seconds).  
The reconstituted solution contains approximately 24 mg/ml docetaxel and should be used immediately after 
preparation.  
 

 
Preparation of the infusion solution 

After reconstitution, each vial contains an extractable volume of approx 3.36 ml concentrate, corresponding 
to approximately 80 mg docetaxel. 
 
The volume of concentrate (24 mg/ml docetaxel) corresponding to the required dose (mg) for the patient 
should be withdrawn (from the appropriate number of vials) using graduated syringes fitted with a needle.  
 
This volume of concentrate should be injected into a 250 ml infusion bag or bottle containing either glucose 
50 mg/ml (5%) solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. 
 
If a dose greater than 200 mg docetaxel is required, a larger volume of the infusion vehicle should be used, 
so that a concentration of 0.74 mg/ml docetaxel is not exceeded in the final solution for infusion. 
 
The solution in the infusion bag or bottle should be allowed to mix manually using a rocking motion. 
 

 
Method of administration  

The docetaxel infusion solution should be used within 4 hours and should be aseptically administered as a 
1 hour infusion under room temperature and normal lighting conditions. 
 

 
Disposal 

Any unused product or waste material should be disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel: +31-23-5685501 
fax: +31-23-5685505 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/630/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 10 May 2010 
 



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10. DATE OF REVISION OF THE TEXT 
 
 
 
 
Detailed information on this product is available on the website of the European Medicines Agency (EMA): 
http://www.ema.europa.eu.



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ANNEX II 
 

A.  MANUFACTURING AUTHORISATION HOLDER 
RESPONSIBLE FOR BATCH RELEASE 
 

B.  CONDITIONS OF THE MARKETING AUTHORISATION 



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A.  MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH 

RELEASE 
 

 
Name and address of the manufacturer responsible for batch release 

Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH  Hoofddorp 
The Netherlands 
 
B.  CONDITIONS OF THE MARKETING AUTHORISATION 
 
• CONDITIONS OF RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON 

THE MARKETING AUTHORISATION HOLDER 
 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2) 
 
• CONDITIONS OF RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 

USE OF THE MEDICINAL PRODUCT 
 

Not applicable. 
 
• OTHER CONDITIONS 
 
Pharmacovigilance system 
 
The MAH must ensure that the system of pharmacovigilance, as described in version 6 (dated January 
2010) presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning 
before and whilst the product is on the market. 

Risk Management plan 
 
Not applicable. The application is based on a reference medicinal product for which no safety concerns 
requiring additional risk minimization activities have been identified. 

PSURs 
The PSUR submission schedule should follow the PSUR schedule for the reference product. 



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ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



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A. LABELLING 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton 20 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Docefrez 20 mg powder and solvent for concentrate for solution for infusion 
Docetaxel 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each single-dose vial of  powder contains 20 mg docetaxel (anhydrous). After reconstitution, 1 ml of 
concentrate contains 24 mg docetaxel.  
 
 
3. LIST OF EXCIPIENTS 
 
Solvent: 
Polysorbate 80 and ethanol, anhydrous  
 
See leaflet for further information. 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for concentrate for solution for infusion 
1 vial of powder 
1 vial of solvent 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 

Dilute before use. For single use only. 
 
 
Read the package leaflet before use. 
 
Intravenous use, after reconstitution and dilution. 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
CYTOTOXIC.  
Special handling precautions. 
 
8. EXPIRY DATE 
 
EXP 



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9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator 
Do not freeze 
Keep the vial in the outer carton 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 
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/630/001 
 
 
13. BATCH NUMBER 
 
Batch  
 
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 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Powder Vial Label 20 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Docefrez 20 mg powder for concentrate for solution for infusion 
Docetaxel 
 
Intravenous use 
 
2. METHOD OF ADMINISTRATION 
 
Dilute before use. 
Read the package leaflet before use. 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
 
Batch  
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
20 mg doxetaxel (anhydrous) 
 
After reconstitution, 1ml of concentrate contains 24 mg docetaxel (anhydrous).  
 
6. OTHER 
 
Sun Pharmaceutical Industries Europe B.V. 
 
CYTOTOXIC 
Special handling precautions 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Solvent Vial Label for Docefrez 20 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Solvent for Docefrez 20 mg 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
3. EXPIRY DATE 
 
EXP: 
 
4. BATCH NUMBER 
 
Batch : 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 ml (35.4% w/w ethanol in polysorbate 80)  
 
6. OTHER 
 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Carton 80 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Docefrez 80 mg powder and solvent for concentrate for solution for infusion 
Docetaxel 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each single-dose vial of powder contains 80 mg docetaxel (anhydrous)  After reconstitution 1 ml of 
concentrate contains 24 mg docetaxel.  
 
3. LIST OF EXCIPIENTS 
 
Solvent: 
Polysorbate 80 and ethanol, anhydrous  
 
See leaflet for further information. 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for concentrate for solution for infusion  
1 vial of powder 
1 vial of solvent 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 

Dilute before use. For single use only. 
 
 
Read the package leaflet before use . 
 
Intravenous use, after reconstitution and  dilution. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
CYTOTOXIC 
Special handling precautions 
 
8. EXPIRY DATE 
 
EXP 



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9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator 
Do not freeze 
Keep the vial in the outer carton 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 
 
Any unused product or waste material should be disposed of in accordance with local requirements 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands. 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/630/002 
 
 
 
13. BATCH NUMBER 
 
Batch 
 
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 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Powder Vial Label 80 mg 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Docefrez 80 mg powder for concentrate for solution for infusion 
Docetaxel 
 
Intravenous use 
 
2. METHOD OF ADMINISTRATION 
 
Dilute before use 
Read the package leaflet before use. 
 
3. EXPIRY DATE 
 
EXP: 
 
4. BATCH NUMBER 
 
Batch: 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
80 mg docetaxel (anhydrous) 
 
After reconstitution, 1 ml of  concentrate contains 24 mg docetaxel (anhydrous).  
6. OTHER 
 
Sun Pharmaceutical Industries Europe B.V. 
 
CYTOTOXIC 
Special handling precautions 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Solvent Vial Label for Docefrez 80 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
 
Solvent for Docefrez 80 mg  
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use 
 
3. EXPIRY DATE 
 
EXP: 
 
4. BATCH NUMBER 
 
Batch: 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
4 ml (35.4% w/w ethanol in polysorbate 80)  
 
 
6. OTHER 
 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH  Hoofddorp 
The Netherlands



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B. PACKAGE LEAFLET 
 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Docefrez 20 mg powder and solvent for concentrate for solution for infusion 
Docetaxel 

 
Read all of this leaflet carefully before you start using this medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or nurse. 
- If  any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please 

tell your doctor or nurse. 
 
In this leaflet:  
 
1. What Docefrez is and what it is used for 
2. Before you use Docefrez 
3. How to use Docefrez 
4. Possible side-effects 
5. How to store Docefrez 
6. Further information 
 
1. WHAT DOCEFREZ  IS AND WHAT IT IS USED FOR 
 
Docefrez contains the active substance docetaxel. Docetaxel, derived from yew-tree needles, belongs to a 
group of anti-cancer medicines called taxanes. 
 
Docefrez is used, either alone or in combination with other medicines, for the treatment of the following 
kinds of cancer:  
- advanced breast cancer, alone or with doxorubicin, or trastuzumab, or capecitabine 
- early breast cancer with or without lymph node involvement, with doxorubicin and cyclophosphamide 
- non-small cell lung cancer (NSCLC), alone or with cisplatin 
- prostate cancer, with prednisone or prednisolone 
- metastatic gastric cancer, with cisplatin and 5-fluorouracil 
- head and neck cancer, with cisplatin and 5-fluorouracil. 
 
 
2. BEFORE YOU USE DOCEFREZ 
 
Do not use Docefrez 
 
- if you are allergic (hypersensitive) to docetaxel or any of the other ingredients of Docefrez 
- if your number of white blood cells is too low 
- if you have  severe liver disease 
- 
 
Take special care with Docefrez 
 
Tell your doctor if you have: 
- heart problems  
- liver problems 
- kidney problems 
 
Before each Docefrez dose, you will have blood tests to check that your blood cell counts and liver function 
are adequate. 
 
 
Using other medicines 



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Please tell your doctor or nurse if you are taking or have recently taken any other medicines, including 
medicines obtained without a prescription.  
In particular, tell your doctor if you are using medicines containing any of the following active substances: 
- ritonavir and other protease inhibitors, used to treat HIV infection/AIDS 
- ketoconazole and itraconazole, used to treat fungal infections 
- ciclosporin, used to suppress your immune system (e.g. after transplants) 
- erythromycin, antibiotic used for bacterial infections 
 
Pregnancy  
 
Ask your doctor for advice before being given any medicine. 
 
You must not use Docefrez 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 Docefrez may be harmful for the unborn baby. If pregnancy occurs 
during your treatment, you must immediately inform your doctor. 
 
If you are a man being treated with Docefrez 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. 
 
Breast-feeding 
 
You must not breast-feed while using Docefrez. 
 
Driving and using machines 
 
There are no studies on the effects of Docefrez on the ability to drive and use machines. However, given that 
it can cause dizziness, tiredness and fainting, you should not drive or use machines if you experience any of 
these side effects. 
 
Important information about some of the ingredients of Docefrez 
 
The solvent contains small amounts of ethanol (alcohol), less than 100 mg per dose. 
 
 
3. HOW TO USE DOCEFREZ 
 
Your doctor will calculate your dose according to your body surface area in square metres (depends on 
weight and height) and your general condition.  
 
You will be given Docefrez by a healthcare professional in the hospital. It is administered through a drip 
into a vein (intravenous infusion) for about one hour. You should usually receive your Docefrez infusion 
every three weeks. 
 
Your doctor may change the dose and/or frequency of administration depending on the results of your blood 
tests, your general condition and the occurence of certain side effects. Tell your doctor or nurse if you have 
fever, diarrhoea, sores in the mouth, feeling of numbness or pins and needles. 
 
Your doctor may prescribe you other medicines before or during treatment with Docefrez: 
- to minimise allergic reactions and fluid retention (pre-treatment with an oral corticoid such as 
dexamethasone), 
- to stimulate your bone marrow to produce more blood cells (e.g. filgrastim). 
 



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If you have any further questions on the use of this medicine, ask your doctor or nurse. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Docefrez can cause side effects, although not everybody gets them. 
 
Side effects may occur with certain frequencies, which are defined as follows:   
- very common: affects more than 1 user in 10  
- common: affects 1 to 10 users in 100  
- uncommon: affects 1 to 10 users in 1,000  
- rare: affects 1 to 10 users in 10,000  
- very rare: affects less than 1 user in 10,000  
- not known: frequency cannot be estimated from the available data. 
 
The most frequent side effects of Docefrez, when given alone, are decrease in the number of red blood cells 
or white blood cells, alopecia, nausea, vomiting, sores in the mouth, diarrhoea and tiredness (all very 
common). 
 
Tell your doctor or nurse immediately during or shortly after the infusion, you notice any of the following 
symptoms of allergic reactions (very common): 
- flushing, skin reactions, itching 
- chest tightness, difficulty in breathing 
- fever or chills 
- back pain 
- low blood pressure. 
 
 
Other very common side effects: 

• fever*: tell your doctor or nurse immediately 
• infections, including pneumonia and blood poisoning  
• decreased number of red bloods cells (anaemia, with symptoms of such as paleness, weakness)  
• decreased number of white blood cells (may make you more prone to infections) 
• decreased number of platelets (increased risk of unexpected bleedings) 
• allergic reactions (see above) 
• headache* , insomnia* 
• feeling of numbness or pins and needles, taste disturbances (due to nerve damage) 
• pain in the joints or muscles 
• inflammation of the eye or increased watering of the eyes 
• swelling caused by fluids from the lymph nodes spreading to uncommon  places 
• swelling of the hands, feet, legs 
• shortness of breath, cough* 
• dripping or running nose; inflammation of the throat and nose* 
• bleeding from the nose 
• sores in the mouth 
• nausea, vomiting, indigestion*, bellyache* 
• diarrhoea, constipation* 
• hair loss  
• redness and swelling of the palms of your hands or soles of your feet which may cause 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* 
• tiredness, pain, flu-like symptoms* 



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• loss of appetite (anorexia), weight gain or loss* 
 
Common side effects: 

• fungal infection of the mouth (oral candidiasis) 
• dehydration 
• dizziness, hearing impaired 
• decrease in blood pressure (hypotension), heart failure; irregular heart beat (arrhythmia) 
• dry mouth, difficulty or painful swallowing,  inflammation of the gullet (oesophagitis) 
• bleeding 
• raised liver enzymes (in blood tests) 

 
Uncommon side effects: 

• fainting 
• at the injection site; skin reactions, inflammation of the vein or swelling 
• inflammation of the colon, small intestine; intestinal perforation 
• blood clots. 

 
When Docefrez is given in combination with other anti-cancer medicines, the frequency or severity of some 
side effects may increase. Side effects marked with “*” have been reported when Docefrez was given in 
combination. 
 
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,  please tell 
your doctor or nurse. 
 
 
5. HOW TO STORE DOCEFREZ 
 
Keep out of the reach and sight of children. 
 
Do not use Docefrez after the expiry date which is stated on the carton and vial after EXP. 
The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2ºC - 8ºC). 
Do not freeze. 
Keep the vial in the outer carton in order to protect from light. 
 
The reconstituted solution should be used immediately after preparation.  
 
Chemical and physical in-use stability of the reconstituted solution has been demonstrated for 8 hours when 
stored either between 2°C and 8°C or below 25°C and for the final solution for infusion for 4 hours at room 
temperature. 
 
The infusion should be used within 4 hours below 25 ºC. 
 
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to 
dispose of medicines no longer required. These measures will help to protect the environment. 
 
 
6. FURTHER INFORMATION 
 
What Docefrez contains 
 
- The active substance is docetaxel.  

[Docefrez 20 mg powder and solvent for concentrate for solution for infusion] Each vial contains 



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20 mg docetaxel (anhydrous). After reconstitution, 1 ml of concentrate contains 24 mg docetaxel. 
The solvent contains 35.4% w/w ethanol and polysorbate 80. 

 
What Docefrez looks like and contents of the pack 
 
Docefrez 20 mg powder and solvent for concentrate for solution for infusion: 
Powder vial: Docefrez is a white lyophilised powder, supplied in a colourless glass vial with a grey 
non-latex rubber stopper and a green aluminium seal. 
Solvent vial: 1 ml clear, colourless solution supplied in a glass vial with a grey non-latex rubber stopper and 
a blue aluminium seal. 
 
Each pack contains: 1 powder vial and 1 solvent vial.  
 
 
Marketing Authorisation Holder and Manufacturer 
 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 
For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 
België/Belgique/Belgien 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

 
Luxembourg/Luxemburg 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

България 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Magyarország 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Česká republika 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Malta 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Danmark 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Nederland 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Deutschland 
SUN Pharmaceuticals Germany GMBH 
Kandelstrasse 7 

Norge 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 



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79199 Kirchzarten 
Germany 
tel. +49 (0) 7661 90 91 58-0 
 

2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Eesti 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Österreich 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Ελλάδα 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Polska 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

España 
SUN Pharmaceuticals Spain S.L. 
C/Bobinadora 1-5 Planta 1a Local 13 
Mataro, 08302 
Barcelona 
Spain 
tel. +34 93 798 02 85 
 

Portugal 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

France 
SUN Pharmaceuticals France 
34, Rue Jean Mermoz 
78600 Maisons Laffitte 
France 
tel. +33 6 48 27 05 59 

România 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Ireland 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Slovenija 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Ísland 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Slovenská republika 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Italia 
SUN Pharmaceuticals Italia S.R.L. 
Via Luigi Rizzo, 8 
I-20151 – Milano 
Italy 
tel. +39 02 33 49 07 93 

Suomi/Finland 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Κύπρος 
Sun Pharmaceutical Industries Europe B.V. 

Sverige 
Sun Pharmaceutical Industries Europe B.V. 



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Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Latvija 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

United Kingdom 
SUN Pharmaceuticals UK Ltd. 
1200 Century Way 
Thorpe Business Park 
Colton, Leeds LS15 8ZA 
United Kingdom 
tel. +44 113 251 59 27 

Lietuva 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 

 

 
This leaflet was last approved in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
://www.ema.europa.eu 
 

http://www.ema.europa.eu/�


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The following information is intended for medical or healthcare professionals only: 
 

PREPARATION GUIDE FOR USE WITH DOCEFREZ 20 MG, POWDER AND SOLVENT FOR 
CONCENTRATE FOR SOLUTION FOR INFUSION 

It is important that you read the entire contents of this procedure prior to the preparation of either the 
Docefrez reconstituted solution or the Docefrez solution for infusion. 

1. FORMULATION 

The Docefrez 20 mg powder is a white to off white lyophilised powder containing 20 mg (plus 22% overfill: 
24.4 mg) of docetaxel (anhydrous). The solvent for Docefrez is a 35.4% w/w solution of ethanol 
(anhydrous) in polysorbate 80. After reconstitution, 1 ml of concentrate contains 24 mg docetaxel. 

2. PRESENTATION 

Docefrez is supplied as single-dose vials. 

Each pack of Docefrez 20 mg powder for concentrate for solution for infusion contains one single-dose vial 
of docetaxel (anhydrous) (20 mg with corresponding fill of 24.4 mg as lyophilised powder) and a 
corresponding single-dose vial with 1 ml of solvent consisting of 35.4% (w/w)of Ethanol (anhydrous)  in 
Polysorbate 80. 

The overfill ensures that after dilution with the entire extractable volume of the accompanying solvent vial 
for Docefrez, there is a minimal extractable reconstituted solution of 0.84 ml containing 20 mg docetaxel 
(anhydrous). 

Docefrez vials should be stored in a refrigerator. Do not freeze. Docefrez should not be used after the expiry 
date shown on the carton and vials. 

2.1 Docefrez 20 mg powder vials 

Docefrez 20 mg powder for concentrate for solution for infusion 

• The Docefrez 20 mg vial contains a white to off white lyophilised powder in a 5 ml tubular colourless 
glass vial with 20 mm grey rubber stopper and sealed with dark green flip-off aluminium seal. 

• Each vial of Docefrez 20 mg contains 20 mg docetaxel (anhydrous) (plus 22% overfill: 24.4 mg 
docetaxel). 

2.2 Docefrez 20 mg solvent vials 

The solvent for Docefrez is 35.4% w/w Ethanol in Polysorbate 80. 

Solvent for Docefrez 20 mg, Powder for Solution for Infusion 

• The solvent vial for Docefrez 20 mg is a 1 ml colourless type 1 tubular glass vial with 20 mm grey 
bromobutyl rubber stopper sealed with 20 mm dark blue flip-off aluminium seal. 

• Each solvent vial of Docefrez 20 mg contains 1 ml of 35.4% w/w Ethanol in Polysorbate 80 



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The overfills are included to ensure that, after dilution with the entire volume of the accompanying solvent 
vial, the minimum extractable volume of reconstituted concentrate containing 20 mg or 80 mg docetaxel, 
respectively, may be withdrawn from the vial. 

 
3. RECOMMENDATIONS FOR THE SAFE HANDLING 

Docefrez is an antineoplastic agent and, as with other potentially toxic compounds, caution should be 
exercised when handling it and preparing Docefrez solutions. The use of gloves is recommended. 

If Docefrez powder, reconstituted solution or infusion solution should come into contact with skin, wash 
immediately and thoroughly with soap and water. If Docefrez powder, reconstituted solution or infusion 
solution should come into contact with mucous membranes, wash immediately and thoroughly with water. 

4. PREPARATION FOR INTRAVENOUS ADMINISTRATION 

Do not use any PVC equipment or device. Docefrez is incompatible with PVC equipment or devices. 

Docefrez powder and solvent for concentrate for solution for infusion is for single use only. 

4.1 Reconstitution of Docefrez Powder for Solution for Infusion 

4.1.1 Allow the required number of Docefrez boxes which are stored in a refrigerator, to stand at room 
temperature (below 25ºC) for 5 minutes. 

 
 
 
 
 
 
 
 
 
 
 
 

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

 
 
 
 
 
 
 
 
 
 
 

 
4.1.3 Inject the entire contents of the syringe into the corresponding Docefrez vial. 
 
 



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4.1.4 Remove the syringe and needle and shake well for complete solubilisation of powder. 
 
 

 
 
 
 
 
 
 
 
 
 
 
 

4.1.5 Allow the reconstituted vial to stand for 5 minutes at room temperature (below 25ºC) and then check 
that the solution is homogenous and clear. 
 
The reconstituted solution contains approximately 24 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). 

 

 

 
 
 
 
 
 
 
 
 



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4.2 Preparation of the infusion solution 

4.2.1 More than one vial of reconstituted solution 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 
volume from the appropriate number of reconstituted solutions using graduated syringes fitted with a needle. 
For example, a dose of 140 mg docetaxel would require one 80 mg and three 20 mg packs. The reconstituted 
solution contains ~ 24 mg/ml docetaxel, corresponding with an extractable volume of approximately 
20 mg/0.84 ml and 80 mg/3.36 ml. 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 

4.2.2 Inject the required volume of reconstituted solution into a 250 ml infusion bag or bottle containing 
either 5% glucose solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. If a dose greater than 
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. 
 
 

 
 
 
 
 
 
 
 
 
 
 
 

 



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4.2.3 Mix the infusion bag or bottle manually using a rocking motion. 
 

 
 
 
 
 
 
 
 
 
 
 
 
 

 
4.2.4 The Docefrez 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, Docefrez reconstituted solution and solution for infusion should be 
visually inspected prior to use, solutions containing a precipitate should be discarded. 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 

5. DISPOSAL 
 
All materials that have been utilised for dilution and administration and any unused product should be 
disposed of in accordance with local requirements. 
 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Docefrez 80 mg powder and solvent for concentrate for solution for infusion 
Docetaxel 

 
Read all of this leaflet carefully before you start using this medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or nurse. 
- If  any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please 

tell your doctor or nurse. 
 
In this leaflet:  
 
1. What Docefrez is and what it is used for 
2. Before you use Docefrez 
3. How to use Docefrez 
4. Possible side-effects 
4 How to store Docefrez 
5 Further information 
 
1 WHAT DOCEFREZ  IS AND WHAT IT IS USED FOR 
 
Docefrez contains the active substance docetaxel. Docetaxel, derived from yew-tree needles, belongs to a 
group of anti-cancer medicines called taxanes. 
 
Docefrez is used, either alone or in combination with other medicines, for the treatment of the following 
kinds of cancer:  
- advanced breast cancer, alone or with doxorubicin, or trastuzumab, or capecitabine 
- early breast cancer with or without lymph node involvement, with doxorubicin and cyclophosphamide 
- non-small cell lung cancer (NSCLC), alone or with cisplatin 
- prostate cancer, with prednisone or prednisolone 
- metastatic gastric cancer, with cisplatin and 5-fluorouracil 
- head and neck cancer, with cisplatin and 5-fluorouracil. 
 
 
2 BEFORE YOU USE DOCEFREZ 
 
Do not use Docefrez 
 
- if you are allergic (hypersensitive) to docetaxel or any of the other ingredients of Docefrez 
- if your number of white blood cells is too low 
- if you have  severe liver disease 
 
 
Take special care with Docefrez 
 
Tell your doctor if you have: 
- heart problems  
- liver problems 
- kidney problems 
 
Before each Docefrez dose, you will have blood tests to check that your blood cell counts and liver function 
are adequate. 
 
 
Using other medicines 



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Please tell your doctor or nurse if you are taking or have recently taken any other medicines, including 
medicines obtained without a prescription.  
In particular, tell your doctor if you are using medicines containing any of the following active substances: 
- ritonavir and other protease inhibitors, used to treat HIV infection/AIDS 
- ketoconazole and itraconazole, used to treat fungal infections 
- ciclosporin, used to suppress your immune system (e.g. after transplants) 
- erythromycin, antibiotic used for bacterial infections 
 
Pregnancy  
 
Ask your doctor for advice before being given any medicine. 
 
You must not use Docefrez 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 Docefrez may be harmful for the unborn baby. If pregnancy occurs 
during your treatment, you must immediately inform your doctor. 
 
If you are a man being treated with Docefrez 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. 
 
Breast-feeding 
 
You must not breast-feed while using Docefrez. 
 
Driving and using machines 
 
There are no studies on the effects of Docefrez on the ability to drive and use machines. However, given that 
it can cause dizziness, tiredness and fainting, you should not drive or use machines if you experience any of 
these side effects. 
 
Important information about some of the ingredients of Docefrez 
 
The solvent contains small amounts of ethanol (alcohol), less than 100 mg per dose. 
 
 
3 HOW TO USE DOCEFREZ 
 
Your doctor will calculate your dose according to your body surface area in square metres (depends on 
weight and height) and your general condition.  
 
You will be given Docefrez by a healthcare professional in the hospital. It is administered through a drip 
into a vein (intravenous infusion) for about one hour. You should usually receive your Docefrez infusion 
every three weeks. 
 
Your doctor may change the dose and/or frequency of administration depending on the results of your blood 
tests, your general condition and the occurence of certain side effects. Tell your doctor or nurse if you have 
fever, diarrhoea, sores in the mouth, feeling of numbness or pins and needles. 
 
Your doctor may prescribe you other medicines before or during treatment with Docefrez: 
- to minimise allergic reactions and fluid retention (pre-treatment with an oral corticoid such as 
dexamethasone), 
- to stimulate your bone marrow to produce more blood cells (e.g. filgrastim). 
 



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If you have any further questions on the use of this medicine, ask your doctor or nurse. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Docefrez can cause side effects, although not everybody gets them. 
 
Side effects may occur with certain frequencies, which are defined as follows:   
- very common: affects more than 1 user in 10  
- common: affects 1 to 10 users in 100  
- uncommon: affects 1 to 10 users in 1,000  
- rare: affects 1 to 10 users in 10,000  
- very rare: affects less than 1 user in 10,000  
- not known: frequency cannot be estimated from the available data. 
 
The most frequent side effects of Docefrez, when given alone, are decrease in the number of red blood cells 
or white blood cells, alopecia, nausea, vomiting, sores in the mouth, diarrhoea and tiredness (all very 
common). 
 
Tell your doctor or nurse immediately during or shortly after the infusion, you notice any of the following 
symptoms of allergic reactions (very common): 
- flushing, skin reactions, itching 
- chest tightness, difficulty in breathing 
- fever or chills 
- back pain 
- low blood pressure. 
 
 
Other very common side effects: 

• fever*: tell your doctor or nurse immediately 
• infections, including pneumonia and blood poisoning  
• decreased number of red bloods cells (anaemia, with symptoms of such as paleness, weakness)  
• decreased number of white blood cells (may make you more prone to infections) 
• decreased number of platelets (increased risk of unexpected bleedings) 
• allergic reactions (see above) 
• headache* , insomnia* 
• feeling of numbness or pins and needles, taste disturbances (due to nerve damage) 
• pain in the joints or muscles 
• inflammation of the eye or increased watering of the eyes 
• swelling caused by fluids from the lymph nodes spreading to uncommon  places 
• swelling of the hands, feet, legs 
• shortness of breath, cough* 
• dripping or running nose; inflammation of the throat and nose* 
• bleeding from the nose 
• sores in the mouth 
• nausea, vomiting, indigestion*, bellyache* 
• diarrhoea, constipation* 
• hair loss  
• redness and swelling of the palms of your hands or soles of your feet which may cause 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* 
• tiredness, pain, flu-like symptoms* 



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• loss of appetite (anorexia), weight gain or loss* 
 
Common side effects: 

• fungal infection of the mouth (oral candidiasis) 
• dehydration 
• dizziness, hearing impaired 
• decrease in blood pressure (hypotension), heart failure; irregular heart beat (arrhythmia) 
• dry mouth, difficulty or painful swallowing,  inflammation of the gullet (oesophagitis) 
• bleeding 
• raised liver enzymes (in blood tests) 

 
Uncommon side effects: 

• fainting 
• at the injection site; skin reactions, inflammation of the vein or swelling 
• inflammation of the colon, small intestine; intestinal perforation 
• blood clots. 

 
When Docefrez is given in combination with other anti-cancer medicines, the frequency or severity of some 
side effects may increase. Side effects marked with “*” have been reported when Docefrez was given in 
combination. 
 
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell 
your doctor or nurse. 
 
 
5. HOW TO STORE DOCEFREZ 
 
Keep out of the reach and sight of children. 
 
Do not use Docefrez after the expiry date which is stated on the carton and vial after EXP. 
The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2ºC - 8ºC). 
Do not freeze. 
Keep the vial in the outer carton in order to protect from light. 
 
The reconstituted solution should be used immediately after preparation.  
 
Chemical and physical in-use stability of the reconstituted solution has been demonstrated for 8 hours when 
stored either between 2°C and 8°C or below 25°C and for the final solution for infusion for 4 hours at room 
temperature. 
 
The infusion should be used within 4 hours below 25 ºC. 
 
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to 
dispose of medicines no longer required. These measures will help to protect the environment. 
 
 
6. FURTHER INFORMATION 
 
What Docefrez contains 
 
- The active substance is docetaxel.  

[Docefrez 80 mg powder and solvent for concentrate for solution for infusion] Each vial contains 



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80 mg docetaxel (anhydrous). After reconstitution, 1 ml of concentrate contains 24 mg docetaxel. The 
solvent contains 35.4% w/w ethanol and polysorbate 80. 

 
What Docefrez looks like and contents of the pack 
 
Docefrez 80 mg powder and solvent for concentrate for solution for infusion: 
Powder vial: Docefrez is a white lyophilised powder, supplied in a colourless glass vial with a grey 
non-latex rubber stopper and a red aluminium seal. 
Solvent vial: 4 ml clear, colourless solution supplied in a glass vial with a grey non-latex rubber stopper and 
a brown aluminium seal. 
 
Each pack contains: 1 powder vial and 1 solvent vial.  
 
 
Marketing Authorisation Holder and Manufacturer 
 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 
For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 
België/Belgique/Belgien 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

 
Luxembourg/Luxemburg 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

България 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Magyarország 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Česká republika 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Malta 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Danmark 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Nederland 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Deutschland 
SUN Pharmaceuticals Germany GMBH 
Kandelstrasse 7 

Norge 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 



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79199 Kirchzarten 
Germany 
tel. +49 (0) 7661 90 91 58-0 
 

2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Eesti 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Österreich 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Ελλάδα 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Polska 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

España 
SUN Pharmaceuticals Spain S.L. 
C/Bobinadora 1-5 Planta 1a Local 13 
Mataro, 08302 
Barcelona 
Spain 
tel. +34 93 798 02 85 
 

Portugal 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

France 
SUN Pharmaceuticals France 
34, Rue Jean Mermoz 
78600 Maisons Laffitte 
France 
tel. +33 6 48 27 05 59 

România 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Ireland 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Slovenija 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Ísland 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Slovenská republika 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Italia 
SUN Pharmaceuticals Italia S.R.L. 
Via Luigi Rizzo, 8 
I-20151 – Milano 
Italy 
tel. +39 02 33 49 07 93 

Suomi/Finland 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Κύπρος 
Sun Pharmaceutical Industries Europe B.V. 

Sverige 
Sun Pharmaceutical Industries Europe B.V. 



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Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

Latvija 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 
 

United Kingdom 
SUN Pharmaceuticals UK Ltd. 
1200 Century Way 
Thorpe Business Park 
Colton, Leeds LS15 8ZA 
United Kingdom 
tel. +44 113 251 59 27 

Lietuva 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
tel. +31 (0)23 568 5501 

 

 
This leaflet was last approved in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
://www.ema.europa.eu 
 

http://www.ema.europa.eu/�


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The following information is intended for medical or healthcare professionals only: 
 

PREPARATION GUIDE FOR USE WITH DOCEFREZ 80 MG, POWDER AND SOLVENT FOR 
CONCENTRATE FOR SOLUTION FOR INFUSION 

It is important that you read the entire contents of this procedure prior to the preparation of either the 
Docefrez reconstituted solution or the Docefrez solution for infusion. 

1. FORMULATION 

The Docefrez 80 mg powder is a white to off white lyophilised powder containing 80 mg (plus 18% overfill: 
94.4 mg) of docetaxel (anhydrous). The solvent for Docefrez is a solution of  35.4% w/w Ethanol 
(anhydrous) in Polysorbate 80. After reconstitution, 1 ml of concentrate contains 24 mg docetaxel 

2. PRESENTATION 

Docefrez is supplied as single-dose vials. 

Each pack of Docefrez 80 mg powder for concentrate for solution for infusion contains one single-dose vial 
of docetaxel (anhydrous) (80 mg  with corresponding fill of 94.4 mg as lyophilised powder) and a 
corresponding single-dose vial with 4.0 ml of solvent consisting of  35.4% (w/w) of Ethanol (anhydrous)  in 
Polysorbate 80. 

The overfill ensures that after dilution with the entire extractable volume of the accompanying solvent vial 
for Docefrez, there is a minimal extractable reconstituted solution of 3.36 ml containing 80 mg docetaxel 
(anhydrous). 

Docefrez vials should be stored in a refrigerator. Do not freeze. Docefrez should not be used after the expiry 
date shown on the carton and vials. 

2.1 Docefrez 80 mg powder vials 

Docefrez 80 mg, Powder for Concentrate for Solution for Infusion 

• The Docefrez 80 mg vial contains a white to off white lyophilised powder in a 15 ml tubular colourless 
glass vial with 20 mm grey rubber stopper and sealed with red flip-off aluminium seal. 

• Each vial of Docefrez 80 mg contains 80 mg docetaxel (anhydrous) (plus 18% overfill: 94.4 mg 
docetaxel). 

 
2.2 Docefrez 80 mg solvent vials 
 
The solvent for Docefrez is 35.4% w/w Ethanol in Polysorbate 80. 

Solvent for Docefrez 80 mg, Powder for Solution for Infusion 

• The solvent vial for Docefrez 80 mg is a 5 ml colourless type 1 tubular glass vial with 20 mm grey 
bromobutyl rubber stopper sealed with 20 mm brown flip-off aluminium seal. 

• Each solvent vial of Docefrez 80 mg contains 4 ml of 35.4% w/w ethanol in Polysorbate 80. 



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The overfills are included to ensure that, after dilution with the entire volume of the accompanying solvent 
vial, the minimum extractable volume of reconstituted concentrate containing 20 mg or 80 mg docetaxel, 
respectively, may be withdrawn from the vial. 

 
3. RECOMMENDATIONS FOR THE SAFE HANDLING 

Docefrez is an antineoplastic agent and, as with other potentially toxic compounds, caution should be 
exercised when handling it and preparing Docefrez solutions. The use of gloves is recommended. 

If Docefrez powder, reconstituted solution or infusion solution should come into contact with skin, wash 
immediately and thoroughly with soap and water. If Docefrez powder, reconstituted solution or infusion 
solution should come into contact with mucous membranes, wash immediately and thoroughly with water. 

4. PREPARATION FOR INTRAVENOUS ADMINISTRATION 

Do not use any PVC equipment or device. Docefrez is incompatible with PVC equipment or devices. 

Docefrez powder and solvent for concentrate for solution for infusion is for single use only. 

4.1 Reconstitution of Docefrez Powder for Solution for Infusion 

4.1.1 Allow the required number of Docefrez boxes which are stored in a refrigerator, to stand at room 
temperature (below 25ºC) for 5 minutes. 

 
 
 
 
 
 
 
 
 
 
 
 

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

 
 
 
 
 
 
 
 
 
 
 

 
4.1.3 Inject the entire contents of the syringe into the corresponding Docefrez vial. 
 
 



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4.1.4 Remove the syringe and needle and shake well for complete solubilisation of powder. 
 
 

 
 
 
 
 
 
 
 
 
 
 
 

4.1.5 Allow the reconstituted vial to stand for 5 minutes at room temperature (below 25ºC) and then check 
that the solution is homogenous and clear. 
 
The reconstituted solution contains approximately 24 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). 

 

 
 
 
 
 
 
 
 
 



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4.2 Preparation of the infusion solution 

4.2.1 More than one vial of reconstituted solution 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 
volume from the appropriate number of reconstituted solutions using graduated syringes fitted with a needle. 
For example, a dose of 140 mg docetaxel would require one 80 mg and three 20 mg packs. The reconstituted 
solution contains ~ 24 mg/ml docetaxel, corresponding with an extractable volume of approximately 
20 mg/0.84 ml and 80 mg/3.36 ml. 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 

4.2.2 Inject the required volume of reconstituted solution into a 250 ml infusion bag or bottle containing 
either 5% glucose solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. If a dose greater than 
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. 
 
 

 
 
 
 
 
 
 
 
 
 
 
 

 



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4.2.3 Mix the infusion bag or bottle manually using a rocking motion. 
 

 
 
 
 
 
 
 
 
 
 
 
 
 

 
4.2.4 The Docefrez 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, Docefrez reconstituted solution and solution for infusion should be 
visually inspected prior to use, solutions containing a precipitate should be discarded. 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 

5. DISPOSAL 
 
All materials that have been utilised for dilution and administration and any unused product should be 
disposed of in accordance with local requirements. 
 
 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OF THE MARKETING AUTHORISATION
	A. LABELLING
	B. PACKAGE LEAFLET