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Drug Details
Taxceus 20mg/ml concentrate for solution for infusion
- Presentation
Each single dose vial contains docetaxel 20 mg/ml Each 1 ml single dose vial contains 20 mg docetaxel Each 4 ml single dose vial contains 80 mg docetaxel Each 7 ml single dose vial contains 140 mg docetaxel Excipient: Ethanol absolute 400 mg/ml - Description
Concentrate for solution for infusion The concentrate is a clear, pale yellow solution - Indications
Breast cancer
Taxceus in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node- positive breast cancer.
Taxceus 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.
Taxceus 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.
Taxceus in combination with trastuzumab is indicated for the treatment of patients with metastatic breast cancer whose tumors over express HER2 and who previously have not received chemotherapy for metastatic disease.
Taxceus 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
Taxceus is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior chemotherapy.
Taxceus 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
Taxceus in combination with prednisone or prednisolone is indicated for the treatment of patients with hormone refractory metastatic prostate cancer.
Gastric Adenocarcinoma
Taxceus 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
Taxceus 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.
- Adult Dosage
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 dosage
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 hematological 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.
Breast cancer
In the adjuvant treatment of operable node-positive 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 (see also Dosage adjustments during treatment).
For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dosage 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 trial 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 dosage and administration, see trastuzumab summary of product characteristics.
In combination with capecitabine, the recommended dose of docetaxel is 75 mg/m² every three weeks, combined with capecitabine at 1250 mg/m² twice daily (within 30 minutes after a meal) for 2 weeks followed by 1-week rest period. For capecitabine dose calculation according to body surface area, see capecitabine summary of product characteristics.
Non-small cell lung cancer
In chemotherapy naïve patients treated for non-small cell lung cancer, the recommended dose regimen is docetaxel 75 mg/m² immediately followed by cisplatin 75 mg/m² over 30-60 minutes. For treatment after failure of prior platinum-based chemotherapy, the recommended dosage is 75 mg/m² as a single agent.
Prostate cancer
The recommended dose of docetaxel is 75 mg/m². Prednisone or prednisolone 5 mg orally twice daily is administered continuously (see section 5.1).
Gastric adenocarcinoma
The recommended dose of docetaxel is 75 mg/m² as a 1 hour infusion, followed by cisplatin 75 mg/m², as a 1 to 3 hour infusion (both on day 1 only), followed by 5-fluorouracil 750 mg/m² per day given as a 24-hour continuous infusion for 5 days, starting at the end of the cisplatin infusion.
Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and appropriate hydration for cisplatin administration. Prophylactic G-CSF should be used to mitigate the risk of hematological toxicities (See also Dosage adjustments during treatment).
Head and neck cancer
Patients must receive premedication with antiemetics and appropriate hydration (prior to and after cisplatin administration). Prophylactic G-CSF may be used to mitigate the risk of hematological toxicities. All patients on the docetaxel-containing arm of the TAX 323 and TAX 324 studies, received prophylactic antibiotics.
- Induction chemotherapy followed by radiotherapy (TAX 323)
For the induction treatment of inoperable locally advanced squamous cell carcinoma of the head and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m² as a 1 hour infusion followed by cisplatin 75 mg/m² over 1 hour, on day one, followed by 5-fluorouracil as a continuous infusion at 750 mg/m² per day for five days. This regimen is administered every 3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy.
- Induction chemotherapy followed by chemoradiotherapy (TAX 324)
For the induction treatment of patients with locally advanced (technically unresectable, low probability of surgical cure, and aiming at organ preservation) squamous cell carcinoma of the head and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m² as a 1 hour intravenous infusion on day 1, followed by cisplatin 100 mg/m² administered as a 30-minute to 3 hour infusion, followed by 5-fluorouracil 1000 mg/m²/day as a continuous infusion from day 1 to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, patients should receive chemoradiotherapy.
For cisplatin and 5-fluorouracil dose modifications, see the corresponding summary of product characteristics.
Dosage adjustments during treatment
General
Docetaxel should be administered when the neutrophil count is
1,500 cells/mm3. In patients who experienced either febrile neutropenia, neutrophil < 500 cells/mm3 for more than one week, severe or cumulative cutaneous reactions or severe peripheral neuropathy during docetaxel therapy, the dose of docetaxel should be reduced from 100 mg/m² to 75 mg/m² and/or from 75 to 60 mg/m². If the patient continues to experience these reactions at 60 mg/m², the treatment should be discontinued.Adjuvant therapy for breast cancer
In the pivotal trial in patients who received adjuvant therapy for breast cancer and who experienced complicated neutropenia (including prolonged neutropenia, febrile neutropenia, or infection), it was recommended to use G-CSF to provide prophylactic coverage (eg, day 4 to 11) in all subsequent cycles. Patients who continued to experience this reaction should remain on G-CSF and have their docetaxel dose reduced to 60 mg/m².
However, in clinical practice neutropenia could occur earlier. Thus the use of G-CSF should be considered function of the neutropenic risk of the patient and current recommendations. Patients who experience Grade 3 or 4 stomatitis should have their dose decreased to 60 mg/m².
In combination with cisplatin
For patients who are dosed initially at docetaxel 75 mg/m² in combination with cisplatin and whose nadir of platelet count during the previous course of therapy is < 25000 cells/mm3, or in patients who experience febrile neutropenia, or in patients with serious non-hematologic toxicities, the docetaxel dosage in subsequent cycles should be reduced to 65 mg/m². For cisplatin dosage adjustments, see manufacturer's summary of product characteristics.
In combination with capecitabine
• For capecitabine dose modifications, see capecitabine summary of product characteristics.
• For patients developing the first appearance of a 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 a Grade 2 toxicity, or the first appearance of a Grade 3 toxicity, at any time during the treatment cycle, delay treatment until resolved to Grade 0-1, then resume treatment with docetaxel 55 mg/m².
• For any subsequent appearances of toxicities, or any Grade 4 toxicities, discontinue the docetaxel dose.
For trastuzumab dose modifications, see trastuzumab summary of product characteristics
In combination with cisplatin and 5-fluorouracil:
If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite G-CSF use, the docetaxel dose should be reduced from 75 to 60 mg/m². If subsequent episodes of complicated neutropenia occur the docetaxel dose should be reduced from 60 to 45 mg/m². In case of Grade 4 thrombocytopenia the docetaxel dose should be reduced from 75 to 60 mg/m².
Patients should not be retreated with subsequent cycles of docetaxel until neutrophils recover to a level > 1,500 cells/mm3 and platelets recover to a level > 100,000 cells/mm3. Discontinue treatment if these toxicities persist. (See section 4.4).
Recommended dose modifications for gastrointestinal toxicities in patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (5-FU):
Toxicity
Dosage adjustment
Diarrhea grade 3
First episode: reduce 5-FU dose by 20%.
Second episode: then reduce docetaxel dose by 20%.
Diarrhea 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 trials patients who experienced complicated neutropenia (including prolonged neutropenia, febrile neutropenia, or infection), it was recommended to use G-CSF to provide prophylactic coverage (eg, day 6-15) in all subsequent cycles.
Special populations
Patients with hepatic impairment
Based on pharmacokinetic data with docetaxel at 100 mg/m² as single agent, patients who have both elevations of transaminase (ALT and/or AST) greater than 1.5 times the upper limit of the normal range (ULN) and alkaline phosphatase greater than 2.5 times the ULN, the recommended dose of docetaxel is 75 mg/m² (see sections 4.4 and 5.2). For those patients with serum bilirubin > ULN and/or ALT and AST > 3.5 times the ULN associated with alkaline phosphatase > 6 times the ULN, no dose-reduction can be recommended and docetaxel should not be used unless strictly indicated.
In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric adenocarcinoma, the pivotal clinical trial 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.
This medicinal product contains 400 mg ethanol per ml concentrate. This has to be taken into account in high-risk groups such as patients with liver disease.
Children and adolescents
Docetaxel is not recommended for use in children due to insufficient data on safety and/or efficacy.
Elderly
Based on a population pharmacokinetic analysis, there are no special instructions for use in the elderly.
In combination with capecitabine, for patients 60 years of age or more, a starting dose reduction of capecitabine to 75% is recommended (see capecitabine summary of product characteristics)
- Contra Indications
Hypersensitivity to the active substance or to any of the excipients.
Patients with baseline neutrophil count of < 1,500 cells/mm3.
Patients with severe liver impairment (see sections 4.2 and 4.4).
Contraindications for other medicinal products also apply, when combined with docetaxel.
- Interactions
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 medication 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 coadministration. 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.
Taxceus contains 400 mg ethanol per ml concentrate. In higher doses (7.5 ml concentrate (150 mg) contains 3 g ethanol) the amount of alcohol may alter the effects of other medicines.
- Adverse Drug Reactions
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).
• 744 patients 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. Frequencies are defined as: very common (
1/10), common ( 1/100 to < 1/10), uncommon ( 1/1000 to < 1/100), rare ( 1/10000 to < 1/1000), very rare (< 1/10000) 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), anemia, alopecia, nausea, vomiting, stomatitis, diarrhea 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 trial in breast cancer patients failing anthracycline treatment are presented (see capecitabine summary of product characteristics).The following adverse reactions are frequently observed with docetaxel:
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.
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).
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).
Docetaxel 100 mg/m² single agent:
MedDRA System Organ classes
Very common adverse reactions
1/10Common adverse reactions
1/100, < 1/10Uncommon adverse reactions
1/1000, < 1/100Investigations
G3/4 Blood bilirubin increased (<5%);
G3/4 Blood alkaline phosphatase increased (<4%);
G3/4 AST increased (<3%);
G3/4 ALT increased (<2%)
Cardiac disorders
Arrhythmia (G3/4: 0.7%)
Cardiac failure
Blood and the lymphatic system disorders
Neutropenia (G4: 76.4%);
Anaemia (G3/4: 8.9%);
Febrile neutropenia
Thrombocytopenia (G4: 0.2%)
Nervous system disorders
Peripheral sensory neuropathy (G3: 4.1%);
Peripheral motor neuropathy (G3/4: 4%)
Dysgeusia (severe 0.07%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea (severe 2.7%)
Gastrointestinal disorders
Stomatitis (G3/4: 5.3%);
Diarrhoea (G3/4: 4%);
Nausea (G3/4: 4%);
Vomiting (G3/4: 3%)
Constipation (severe 0.2%);
Abdominal pain (severe 1%);
Gastrointestinal Haemorrhage (severe 0.3%)
Oesophagitis (severe: 0.4%)
Skin and subcutaneous tissue disorders
Alopecia;
Skin reaction (G3/4: 5.9%);
Nail disorders (severe 2.6%)
Musculoskeletal, connective tissue and bone disorders
Myalgia (severe 1.4%)
Arthralgia
Metabolism and nutrition disorders
Anorexia
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%)
Vascular disorders
Hypotension;
Hypertension;
Haemorrhage
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%)
Immune system disorders
Hypersensitivity (G3/4: 5.3%)
Blood and Lymphatic system disorders
Rare: bleeding episodes associated with grade 3/4 thrombocytopenia
Nervous system disorders
Reversibility data are available among 35.3% of patients who developed neurotoxicity following docetaxel treatment at 100 mg/m² as single agent. The events were spontaneously reversible within 3 months.
Skin and subcutaneous tissue disorders
Very rare: one case of alopecia non-reversible at the end of the study. 73% of the cutaneous reactions were reversible within 21 days.
General disorders and administration site conditions
The median cumulative dose to treatment discontinuation was more than 1,000 mg/m² and the median time to fluid retention reversibility was 16.4 weeks (range 0 to 42 weeks). The onset of moderate and severe retention is delayed (median cumulative dose: 818.9 mg/m²) in patients with premedication compared with patients without premedication (median cumulative dose: 489.7 mg/m²); however, it has been reported in some patients during the early courses of therapy.
Docetaxel 75 mg/m² single agent:
MedDRA System Organ classes
Very common adverse reactions
1/10Common adverse reactions
1/100, < 1/10Investigations
G3/4 Blood bilirubin increased (<2%)
Cardiac disorders
Arrhythmia (no severe)
Blood and the lymphatic system disorders
Neutropenia (G4: 54.2%);
Anaemia (G3/4: 10.8%);
Thrombocytopenia (G4: 1.7%)
Febrile neutropenia
Nervous system disorders
Peripheral sensory neuropathy (G3/4: 0.8%)
Peripheral motor neuropathy (G3/4: 2.5%)
Gastrointestinal disorders
Nausea (G3/4: 3.3%);
Stomatitis (G3/4: 1.7%);
Vomiting (G3/4: 0.8%);
Diarrhea (G3/4: 1.7%)
Constipation
Skin and subcutaneous tissue disorders
Alopecia;
Skin reaction (G3/4: 0.8%)
Nail disorders (severe 0.8%)
Musculoskeletal, connective tissue and bone disorders
Myalgia
Metabolism and nutrition disorders
Anorexia
Infections and infestations
Infections (G3/4: 5%)
Vascular disorders
Hypotension
General disorders and administration site conditions
Asthenia (severe 12.4%);
Fluid retention (severe 0.8%);
Pain
Immune system disorders
Hypersensitivity (no severe)
Docetaxel 75 mg/m² in combination with doxorubicin:
MedDRA System Organ classes
Very common adverse reactions
1/10Common adverse reactions
1/100, < 1/10Uncommon adverse reactions
1/1,000, < 1/100Investigations
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%)
Cardiac disorders
Cardiac failure; Arrhythmia (no severe)
Blood and the lymphatic system disorders
Neutropenia (G4: 91.7%);
Anaemia (G3/4: 9.4%);
Febrile neutropenia;
Thrombocytopenia (G4: 0.8%)
Nervous system disorders
Peripheral sensory neuropathy (G3: 0.4%)
Peripheral motor neuropathy (G3/4: 0.4%)
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, connective tissue and bone disorders
Myalgia
Metabolism and nutrition disorders
Anorexia
Infections and infestations
Infection (G3/4: 7.8%)
Vascular disorders
Hypotension
General disorders and administration site conditions
Asthenia (severe 8.1%);
Fluid retention (severe 1.2%);
Pain
Infusion site reaction
Immune system disorders
Hypersensitivity (G3/4: 1.2%)
Docetaxel 75 mg/m² in combination with cisplatin:
MedDRA System Organ classes
Very common adverse reactions
1/10Common adverse reactions
1/100, < 1/10Uncommon adverse reactions
1/1,000, < 1/100Investigations
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%)
Cardiac disorders
Arrhythmia (G3/4: 0.7%)
Cardiac failure
Blood and the lymphatic system disorders
Neutropenia (G4: 51.5%);
Anaemia (G3/4: 6.9%);
Thrombocytopenia (G4:0.5%)
Febrile neutropenia
Nervous system disorders
Peripheral sensory neuropathy (G3: 3.7%);
Peripheral motor neuropathy (G3/4: 2%)
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, connective tissue and bone disorders
Myalgia (severe 0.5%)
Metabolism and nutrition disorders
Anorexia
Infections and infestations
Infection (G3/4: 5.7%)
Vascular disorders
Hypotension (G3/4: 0.7%)
General disorders and administration site conditions
Asthenia (severe 9.9%);
Fluid retention (severe 0.7%);
Fever (G3/4: 1.2%)
Infusion site reaction;
Pain
Immune system disorders
Hypersensitivity (G3/4: 2.5%)
Docetaxel 100 mg/m² in combination with trastuzumab:
MedDRA System Organ classes
Very common adverse reactions
1/10Common adverse reactions
1/100, < 1/10Investigations
Weight increased
Cardiac disorders
Cardiac failure
Blood and the lymphatic system disorders
Neutropenia (G3/4: 32%);
Febrile neutropenia (includes neutropenia associated with fever and antibiotic use) or neutropenic sepsis
Nervous system disorders
Paresthesia; Headache; Dysgeusia; Hypoaesthesia
Eye disorders
Lacrimation increased; Conjunctivitis
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, connective tissue and bone disorders
Myalgia; Arthralgia; Pain in extremity; Bone pain; Back pain
Metabolism and nutrition disorders
Anorexia
Vascular disorders
Lymphoedema
General disorders and administration site conditions
Asthenia; Oedema peripheral; Pyrexia; Fatigue; Mucosal inflammation; Pain; Influenza like illness; Chest pain; Chills
Lethargy
Psychiatric disorders
Insomnia
Cardiac disorders
Symptomatic cardiac failure was reported in 2.2% of the patients who received docetaxel plus trastuzumab compared to 0% of patients given docetaxel alone. In the docetaxel plus trastuzumab arm, 64% had received a prior anthracycline as adjuvant therapy compared with 55% in the docetaxel arm alone.
Blood and the lymphatic system disorders
Very common: Haematological toxicity was increased in patients receiving trastuzumab and docetaxel, compared with docetaxel alone (32% grade 3/4 neutropenia versus 22%, using NCI-CTC criteria). Note that this is likely to be an underestimate since docetaxel alone at a dose of 100 mg/m² is known to result in neutropenia in 97% of patients, 76% grade 4, based on nadir blood counts. The incidence of febrile neutropenia/neutropenic sepsis was also increased in patients treated with Herceptin plus docetaxel (23% versus 17% for patients treated with docetaxel alone).
Docetaxel 75 mg/m² in combination with capecitabine:
MedDRA System Organ classes
Very common adverse reactions
1/10Common adverse reactions
1/100, < 1/10Investigations
Weight decreased;
G3/4 Blood bilirubin increased (9%)
Blood and the lymphatic system disorders
Neutropenia (G3/4: 63%);
Anaemia (G3/4: 10%)
Thrombocytopenia (G3/4: 3%)
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, connective tissue and bone disorders
Myalgia (G3/4: 2%);
Arthralgia (G3/4: 1%)
Pain in extremity (G3/4: <1%);
Back pain (G3/4: 1%);
Metabolism and nutrition disorders
Anorexia (G3/4: 1%);
Decreased appetite
Dehydration (G3/4: 2%);
Infections and infestations
Oral candidiasis (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
Docetaxel 75 mg/m² in combination with prednisone or prednisolone:
MedDRA System Organ classes
Very common adverse reactions
1/10Common adverse reactions
1/100, < 1/10Cardiac disorders
Cardiac left ventricular function decrease (G3/4: 0.3%)
Blood and the lymphatic system disorders
Neutropenia (G3/4: 32%);
Anaemia (G3/4: 4.9%)
Thrombocytopenia; (G3/4: 0.6%);
Febrile neutropenia
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%)
Respiratory, thoracic and mediastinal disorders
Epistaxis (G3/4: 0%);
Dyspnoea (G3/4: 0.6%);
Cough (G3/4: 0%)
Gastrointestinal disorders
Nausea (G3/4: 2.4%);
Diarrhoea (G3/4: 1.2%);
Stomatitis/Pharyngitis (G3/4: 0.9%);
Vomiting (G3/4: 1.2%)
Skin and subcutaneous tissue disorders
Alopecia;
Nail disorders (no severe)
Exfoliative rash (G3/4: 0.3%)
Musculoskeletal, connective tissue and bone disorders
Arthralgia (G3/4: 0.3%);
Myalgia (G3/4: 0.3%)
Metabolism and nutrition disorders
Anorexia (G3/4: 0.6%)
Infections and infestations
Infection (G3/4: 3.3%)
General disorders and administration site conditions
Fatigue (G3/4: 3.9%);
Fluid retention (severe 0.6%)
Immune system disorders
Hypersensitivity (G3/4: 0.6%)
Docetaxel 75 mg/m² in combination with doxorubicin and cyclophosphamide:
MedDRA System Organ classes
Very common adverse reactions
1/10Common adverse reactions
1/100, < 1/10Uncommon adverse reactions
1/1,000, < 1/100Investigations
Weight increased or decreased (G3/4: 0.3%)
Cardiac disorders
Arrhythmia (G3/4: 0.1%);
Congestive heart failure
Blood and the lymphatic system disorders
Anaemia (G3/4: 4.3%);
Neutropenia (G3/4: 65.5%);
Thrombocytopenia (G3/4: 2.0%);
Febrile neutropenia
Nervous system disorders
Dysgeusia (G3/4: 0.7%);
Peripheral sensory neuropathy (G3/4: 0%)
Peripheral motor neuropathy (G3/4: 0%);
Neurocortical (G3/4: 0.3%);
Neurocerebellar (G3/4: 0.1%)
Syncope (G3/4: 0%)
Eye disorders
Lacrimation disorder (G3/4: 0.1%);
Conjunctivitis (G3/4: 0.3%)
Respiratory, thoracic and mediastinal disorders
Cough (G3/4: 0%)
Gastrointestinal disorders
Nausea (G3/4: 5.1%);
Stomatitis (G3/4: 7.1%);
Vomiting (G3/4: 4.3%);
Diarrhoea (G3/4: 3.2%);
Constipation (G3/4: 0.4%)
Abdominal pain (G3/4: 0.5%)
Colitis/enteritis/ large intestine perforation
Skin and subcutaneous tissue disorders
Alopecia;
Skin toxicity (G3/4: 0.7%);
Nail disorders (G3/4: 0.4%)
Musculoskeletal, connective tissue and bone disorders
Myalgia (G3/4: 0.8%);
Arthralgia (G3/4: 0.4%)
Metabolism and nutrition disorders
Anorexia (G3/4: 2.2%)
Infections and infestations
Infection (G3/4: 3.2%);
Neutropenic infection.
There were no septic deaths.
Vascular disorders
Vasodilatation (G3/4: 0.9%)
Hypotension (G3/4: 0%)
Phlebitis (G3/4: 0%);
Lymphoedema (G3/4: 0%)
General disorders and administration site conditions
Asthenia (G3/4: 11%);
Fever (G3/4: 1.2%);
Oedema peripheral (G3/4: 0.4%)
Immune system disorders
Hypersensitivity (G3/4: 1.1%)
Reproductive system and breast disorders
Amenorrhoea
Cardiac disorders
Congestive Heart Failure (CHF) (2.3% at 70 months median follow-up) has also been reported. One patient in each treatment arm died due to cardiac failure.
Nervous system disorders
Peripheral sensory neuropathy was observed to be ongoing at the median follow-up time of 55 months in 9 patients out of the 73 patients with peripheral sensory neuropathy at the end of the chemotherapy.
Skin and subcutaneous tissue disorders
Alopecia was observed to be ongoing at the median follow-up time of 55 months in 22 patients out of the 687 patients with alopecia at the end of the chemotherapy.
General disorders and administration site condition
Oedema peripheral was observed to be ongoing at the median follow-up time of 55 months in 18 patients out of the 112 patients with oedema peripheral at the end of the chemotherapy.
Reproductive system and breast disorders
Amenorrhoea was observed to be ongoing at the median follow-up time of 55 months in 133 patients out of the 233 patients with amenorrhoea at the end of the chemotherapy.
Docetaxel 75 mg/m² in combination with cisplatin and 5-fluorouracil for gastric adenocarcinoma cancer:
MedDRA System Organ classes
Very common adverse reactions
1/10Common adverse reactions
1/100, < 1/10Cardiac disorders
Arrhythmia (G3/4: 1.0%).
Blood and the lymphatic system disorders
Anaemia (G3/4: 20.9%);
Neutropenia (G3/4: 83.2%);
Thrombocytopenia (G3/4: 8.8%);
Febrile neutropenia.
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%).
Gastrointestinal disorders
Diarrhoea (G3/4: 19.7%);
Nausea (G3/4: 16%);
Stomatitis (G3/4: 23.7%);
Vomiting (G3/4: 14.3%).
Constipation (G3/4: 1.0 %);
Gastrointestinal pain (G3/4: 1.0%);
Oesophagitis/dysphagia/ odynophagia (G3/4: 0.7%).
Skin and subcutaneous tissue disorders
Alopecia (G3/4: 4.0%).
Rash pruritus (G3/4: 0.7%);
Nail disorders (G3/4: 0.7%);
Skin exfoliation (G3/4: 0%).
Metabolism and nutrition disorders
Anorexia (G3/4: 11.7%).
Infections and infestations
Neutropenic infection;
Infection (G3/4: 11.7%).
General disorders and administration site conditions
Lethargy (G3/4: 19.0%);
Fever (G3/4: 2.3%);
Fluid retention (severe/life threatening: 1%).
Immune system disorders
Hypersensitivity (G3/4: 1.7).
Blood and the lymphatic system disorders
Febrile neutropenia and neutropenic infection occurred in 17.2% and 13.5% of patients respectively, regardless of G-CSF use. G-CSF was used for secondary prophylaxis in 19.3% of patients (10.7% of the cycles). Febrile neutropenia and neutropenic infection occurred respectively in 12.1% and 3.4% of patients when patients received prophylactic G-CSF, in 15.6% and 12.9% of patients without prophylactic G-CSF, (see section 4.2).
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
1/10Common adverse reactions
1/100, < 1/10Uncommon adverse reactions
1/1,000, < 1/100Investigations
Weight increased
Cardiac disorders
Myocardial ischemia (G3/4: 1.7%)
Arrhythmia (G3/4: 0.6%)
Blood and the lymphatic system disorders
Neutropenia (G3/4: 76.3%)
Anemia (G3/4: 9.2)
Thrombocytopenia (G3/4: 5.2%)
Febrile neutropenia
Nervous system disorders
Dysgeusia/Parosmia
Peripheral sensory neuropathy (G3/4: 0.6%)
Dizziness
Eye disorders
Lacrimation increased
Conjunctivitis
Ear and labyrinth disorders
Hearing impaired
Gastrointestinal disorders
Nausea (G3/4:0.6%)
Stomatitis (G3/4: 4.0%)
Diarrhea (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, connective tissue and bone disorders
Myalgia (G3/4: 0.6%)
Metabolism and nutrition disorders
Anorexia (G3/4: 0.6%)
Infections and infestations
Infection (G3/4: 6.3%) Neutropenic infection
Neoplasms benign and malignant (including cysts and polyps)
Cancer pain (G3/4: 0.6%)
Vascular disorders
Venous disorder (G3/4: 0.6%)
General disorders and administration site conditions
Lethargy (G3/4: 3.4%)
Pyrexia (G3/4: 0.6%)
Fluid retention
Oedema
Immune system disorders
Hypersensitivity (no severe)
• Induction chemotherapy followed by chemoradiotherapy (TAX 324)
MedDRA System Organ classes
Very common adverse reactions
1/10Common adverse reactions
1/100, < 1/10Uncommon adverse reactions
1/1,000, < 1/100Investigations
Weight decreased
Weight increased
Cardiac disorders
Arrhythmia (G3/4: 2.0%)
Ischemia myocardial
Blood and the lymphatic system disorders
Neutropenia (G3/4: 83.5%)
Anemia (G3/4: 12.4%)
Thrombocytopenia (G3/4: 4.0%)
Febrile neutropenia
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%)
Gastrointestinal disorders
Nausea (G3/4: 13.9%);
Stomatitis (G3/4: 20.7%);
Vomiting (G3/4: 8.4%);
Diarrhea (G3/4: 6.8%);
Esophagitis/dysphagia/ odynophagia (G3/4: 12.0%);
Constipation (G3/4:0.4%)
Dyspepsia (G3/4: 0.8%);
Gastrointestinal pain (G3/4: 1.2%);
Gastrointestinal haemorrhage (G3/4: 0.4%)
Skin and subcutaneous tissue disorders
Alopecia (G3/4: 4.0%);
Rash pruritic
Dry skin;
Desquamation
Musculoskeletal, connective tissue and bone disorders
Myalgia (G3/4: 0.4%)
Metabolism and nutrition disorders
Anorexia (G3/4: 12.0%)
Infections and infestations
Infection (G3/4: 3.6%)
Neutropenic infection
Neoplasms benign and malignant (including cysts and polyps)
Cancer pain (G3/4: 1.2%)
Vascular disorders
Venous disorder
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%)
Immune system disorders
Hypersensitivity
Post-Marketing Experience:
Cardiac disorders
Rare cases of myocardial infarction have been reported.
Blood and the lymphatic system disorders
Bone marrow suppression and other hematologic adverse reactions have been reported. Disseminated intravascular coagulation (DIC), often in association with sepsis or multiorgan failure, has been reported.
Nervous system disorders
Rare cases of convulsion or transient loss of consciousness have been observed with docetaxel administration. These reactions sometimes appear during the infusion of the medicinal product.
Eye Disorders
Very rare cases of transient visual disturbances (flashes, flashing lights, scotomata) typically occurring during infusion of the medicinal product and in association with hypersensitivity reactions have been reported. These were reversible upon discontinuation of the infusion. Cases of lacrimation with or without conjunctivitis, as cases of lacrimal duct obstruction resulting in excessive tearing have been rarely reported.
Ear and labyrinth disorders
Rare cases of ototoxicity, hearing impaired and/or hearing loss have been reported.
Respiratory, thoracic and mediastinal 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.
Gastrointestinal 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.
Skin and subcutaneous tissue disorders
Very rare cases of cutaneous lupus erythematosus and bullous eruptions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, have been reported with docetaxel. In some cases concomitant factors may have contributed to the development of these effects.
Neoplasms benign, malignant and unspecified (including cysts and polyps)
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.
Vascular disorders
Venous thromboembolic events have rarely been reported.
General disorders and administration site conditions
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
Immune system disorders
Some cases of anaphylactic shock, sometimes fatal, have been reported.
Hepato-biliary disorders
Very rare cases of hepatitis, sometimes fatal primarily in patients with pre-existing liver disorders, have been reported.