Docetaxel is indicated for Breast, Non-Small Cell Lung, Gastric and Head and Neck Cancers, Prostate Cancer, Breast Cancer, Patients with Locally Advanced or Metastatic Breast Cancer, Non-Small Cell Lung Cancer (NSCLC), Prostate Cancer, Gastric Adenocarcinoma, Head and Neck Cancer, Induction Treatment of Inoperable, Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN), Ovarian Cance.
Docetaxel is an antineoplastic agent, which acts by disrupting the microtubular network in cells that is essential for vital mitotic and interphase cellular functions. Docetaxel promotes the assembly of tubulin into stable microtubules while simultaneously inhibiting their disassembly. Docetaxel binds to free tubulin thereby decreasing the critical intracellular concentration of tubulin. The promoted polymerization of microtubules leads to the production of microtubule bundles without normal function and to the stabilization of microtubules, resulting in the inhibition of mitosis in cells. The binding of Docetaxel to microtubules does not alter the number of protofilaments in the bound microtubules; in that, it differs from other spindle poisons. Docetaxel was found to be cytotoxic in vitro against various murine and human tumor cell lines, and against freshly excised human tumor cells in clonogenic assays. In addition, Docetaxel was found to be active on a number of cell lines overexpressing the p-glycoprotein, which is encoded by the multidrug resistant gene.
Breast, non-small cell lung, gastric, head & neck cancers: Premedication consisting of an oral corticosteroid eg dexamethasone 16 mg/day (8 mg twice daily) for 3 days starting 1 day prior to docetaxel administration. Prostate cancer: Given the concurrent use of prednisone or prednisolone, the recommended premedication regimen: Oral dexamethasone 8 mg 12 hr, 3 hr & 1 hr before docetaxel infusion. Administered as 1-hr infusion every 3 wk. Breast cancer: In the adjuvant treatment of operable node +ve: 75 mg/m2 administered 1 hr after doxorubicin 50 mg/m2 & cyclophosphamide 500 mg/m2 every 3 wk for 6 cycles. For the treatment of patients with locally advanced or metastatic breast cancer: 100 mg/m2 in monotherapy. In the 1st-line treatment combination therapy: 75 mg/m2 with doxorubicin (50 mg/m2). In combination with trastuzumab: 100 mg/m2 every 3 wk, administered wkly. In combination with capecitabine: 75 mg/m2 every 3 wk, combined with capecitabine at 1250 mg/m2 twice daily (within 30 min after a meal) for 2 wk followed by a 1-wk rest period. Non-small cell lung cancer: In chemotherapy-naive patients treated for non-small cell lung cancer: 75 mg/m2 immediately followed by cisplatin 75 mg/m2 over 30-60 min. For treatment after failure of prior platinum-based chemotherapy: 75 mg/m2 as a single agent. Prostate cancer: 75 mg/m2. Prednisone or prednisolone 5 mg orally twice daily is administered continuously Gastric adenocarcinoma: 75 mg/m2 as 1-hr infusion, followed by cisplatin 75 mg/m2, as 1-3-hr infusion (both on day 1 only), followed by 5-fluorouracil 750 mg/m2/day given as 24-hr continuous infusion for 5 days, starting at the end of the cisplatin infusion. Head & neck cancer: For the induction treatment of inoperable locally advanced squamous cell carcinoma of the head & neck: 75 mg/m2 as 1-hr infusion followed by cisplatin 75 mg/m2 over 1 hr on day 1, followed by 5-fluorouracil as a continuous infusion at 750 mg/m2 per day for 5 days. Administered every 3 wk for 4 cycles. Following chemotherapy, patients should receive radiotherapy. Ovarian cancer: 75-100 mg/m2 administered as 1-hr infusion every 3 wk.
Docetaxel is a CYP3A4 substrate. In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant administration of compounds that induce, inhibit, or are metabolized by cytochrome P450 3A4.
Severe hypersensitivity to docetaxel. Neutrophil count of <1500 cell/mm3. Severe liver impairment. Pregnancy & lactation. Monitor blood counts. Reduce dose in case of severe neutropenia (2 to 75 mg/m2, &/or from 75 mg/m2 to 60 mg/m2. Monitor patient for hypersensitivity, fluid retention, liver impairment, cardiac toxicity. Contraceptive measures must be taken by both men & women during treatment & for men at least 6 mth after cessation of therapy. Elderly.
Neutropenia, anaemia, alopecia, nausea, asthenia, hypersensitivity, anorexia, neurologic effects, neuropathy, dizziness, dyspnoea, epitaxis, GI effects, skin & cutaneous reactions, myalgia, fluid retention, pain, lacrimation increased, conjunctivitis, lymphoedema, pharyngolaryngeal pain, oedema peripheral, fatigue, vasodilation, amenorrhoea, pyrexia, lethargy, fever, arrhythmia, hypotension, dehydration.
Category D: There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
There were a few reports of overdosage. 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 case of overdosage, exacerbation of adverse events may be expected. The primary anticipated complications of overdosage 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.
Store between 2°C and 25°C and protected from light. Freezing does not adversely affect the product.
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