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 Special precautions for disposal and other handling under Cautions for Usage).
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 Sandoz administration, unless contraindicated, can be used (see Precautions). 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 Sandoz infusion (see Precautions).
Docetaxel Sandoz is administered as a one-hour infusion every three weeks. See Special precautions for disposal and other handling under Cautions for Usage for further details on preparation of infusion solution. Care should be taken of administration of the infusion to avoid extravasation.
Breast cancer: In the adjuvant treatment of operable node-positive breast cancer, the recommended dose of Docetaxel Sandoz 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 Dose adjustments during treatment as follows).
For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose of Docetaxel Sandoz is 100 mg/m2 in monotherapy. In first-line treatment, Docetaxel Sandoz 75 mg/m2 is given in combination therapy with doxorubicin (50 mg/m2).
In combination with trastuzumab the recommended dose of Docetaxel Sandoz 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 dose and administration, see trastuzumab summary of product characteristics.
In combination with capecitabine, the recommended dose of Docetaxel Sandoz is 75 mg/m2 every three weeks, combined with capecitabine of 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 Sandoz 75 mg/m2 immediately followed by cisplatin 75 mg/m2 over 30-60 minutes. For treatment after failure of prior platinum-based chemotherapy, the recommended dose is 75 mg/m2 as a single agent.
Prostate cancer: The recommended dose of Docetaxel Sandoz is 75 mg/m2. Prednisone or prednisolone 5 mg orally twice daily is administered continuously (see Pharmacology: Pharmacodynamics under Actions).
Gastric adenocarcinoma: The recommended dose of Docetaxel Sandoz 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 Dose adjustments during treatment as follows).
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 chemotherapy (TAX 324): For the induction treatment of patients with locally advanced (technically unresectable, low probability of surgical cure, and aiming at organ preservation) squamous cell carcinoma of the head and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m2 as a 1 hour intravenous infusion on day 1, followed by cisplatin 100 mg/m2 administered as a 30-minute to 3 hour infusion, followed by 5-fluorouracil 1000 mg/m2/day as a continuous infusion from day 1 to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, patients should receive chemoradiotherapy.
For cisplatin and 5-fluorouracil dose modifications, see the corresponding summary of product characteristics.
Dose adjustments during treatment: General: Docetaxel Sandoz 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 Sandoz therapy, the dose of Docetaxel Sandoz 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 Sandoz 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-hematologic toxicities, the Docetaxel Sandoz dose in subsequent cycles should be reduced to 65 mg/m2. For cisplatin dose adjustments, see the corresponding summary of product characteristics.
In combination with capecitabine: For capecitabine dose modifications, see capecitabine summary of product characteristics.
For patients developing the first appearance of a Grade 2 toxicity, which persists at the time of the next Docetaxel Sandoz/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 Sandoz 55 mg/m2.
For any subsequent appearances of toxicities, or any Grade 4 toxicities, discontinue the Docetaxel Sandoz 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 Sandoz dose should be reduced from 75 to 60 mg/m2. If subsequent episodes of complicated neutropenia occur the Docetaxel Sandoz dose should be reduced from 60 to 45 mg/m2. In case of Grade 4 thrombocytopenia the Docetaxel Sandoz dose should be reduced from 75 to 60 mg/m2. Patients should not be retreated with subsequent cycles of Docetaxel Sandoz 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 Precautions.)
Recommended dose modifications for toxicities in patients treated with Docetaxel Sandoz in combination with cisplatin and 5-fluorouracil (5-FU): See Table 8.
Click on icon to see table/diagram/image
For cisplatin and 5-fluorouracil dose adjustments, see the corresponding summary of product characteristics.
Special populations: Patients with hepatic impairment: Based on pharmacokinetic data with docetaxel at 100 mg/m2 as a 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 Precautions and Pharmacology: Pharmacokinetics under Actions). 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 x ULN associated with alkaline phosphatase > 2.5 x 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 27 vol % ethanol (alcohol). This has to be taken into account in high-risk groups such as patients with liver disease.
Patients with renal impairment: There are no data available in patients with severely impaired renal function treated with docetaxel.
Children and adolescents: Docetaxel Sandoz is not recommended for use in children due to insufficient data on safety and 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).
Administration: Docetaxel Sandoz is for intravenous use only.