Docetaxel

Docetaxel is a microtubule inhibitor indicated for: Breast Cancer (BC): single agent for locally advanced or metastatic BC after chemotherapy failure, and with doxorubicin and cyclophosphamide as adjuvant treatment of operable node-positive BC. Non-small Cell Lung Cancer (NSCLC): single agent for locally advanced or metastatic NSCLC after platinum therapy failure, and with cisplatin for unresectable, locally advanced or metastatic untreated NSCLC. Castration-Resistant Prostate Cancer (CRPC): with prednisone in metastatic castration-resistant prostate cancer. Gastric Adenocarcinoma (GC): with cisplatin and fluorouracil for untreated, advanced GC, including the gastroesophageal junction. Squamous Cell Carcinoma of the Head and Neck (SCCHN): with cisplatin and fluorouracil for induction treatment of locally advanced SCCHN

Docetaxel is an antineoplastic agent that acts by disrupting the microtubular network in cells that is essential for mitotic and interphase cellular functions. Docetaxel binds to free tubulin and promotes the assembly of tubulin into stable microtubules while simultaneously inhibiting their disassembly. This leads to the production of microtubule bundles without normal function and to the stabilization of microtubules, which results in the inhibition of mitosis in cells. Docetaxel's binding to microtubules does not alter the number of protofilaments in the bound microtubules, a feature which differs from most spindle poisons currently in clinical use.

For all indications, toxicities may warrant dosage adjustments. Administer in a facility equipped to manage possible complications (e.g., anaphylaxis). Administer intravenously (IV) over 1 hr every 3 weeks. PVC equipment is not recommended. Use only a 21 gauge needle to withdraw Docetaxel from the vial. BC locally advanced or metastatic: 60 mg/m 2 to 100 mg/m 2 single agent. BC adjuvant: 75 mg/m 2 administered 1 hour after doxorubicin 50 mg/m 2 and cyclophosphamide 500 mg/m 2 every 3 weeks for 6 cycles. NSCLC: after platinum therapy failure: 75 mg/m 2 single agent. NSCLC: chemotherapy naive: 75 mg/m 2 followed by cisplatin 75 mg/m 2. HRPC: 75 mg/m 2 with 5 mg prednisone twice a day continuously. GC: 75 mg/m 2 followed by cisplatin 75 mg/m 2 (both on day 1 only) followed by fluorouracil 750 mg/m 2 per day as a 24-hr IV (days 1–5), starting at end of cisplatin infusion.

Docetaxel is contraindicated in patients with: neutrophil counts of <1500 cells/mm 3. a history of severe hypersensitivity reactions to docetaxel or to other drugs formulated with polysorbate 80. Severe reactions, including anaphylaxis, have occurred. Hypersensitivity to docetaxel or polysorbate 80. Neutrophil counts of <1500 cells/mm 3

Boxed warning (toxic deaths, hepatotoxicity, neutropenia, hypersensitivity reactions, and fluid retention): Treatment-related mortality associated with Docetaxel therapy is increased in patients with abnormal liver function, in patients receiving higher doses, and in patients with non-small cell lung carcinoma and a history of prior treatment with platinum-based chemotherapy who receive Docetaxel as a single agent at a dose of 100 mg/m 2. Second primary malignancies: In patients treated with Docetaxel-containing regimens, monitor for delayed AML, MDS, NHL, and renal cancer. Cutaneous reactions: Reactions including erythema of the extremities with edema followed by desquamation may occur. Severe cutaneous adverse reactions have been reported. Severe skin toxicity may require dose adjustment or permanent treatment discontinuation.

The most serious adverse reactions from docetaxel are: Toxic Deaths Hepatic Impairment Hematologic Effects Enterocolitis and Neutropenic Colitis Hypersensitivity Reactions Fluid Retention Second Primary Malignancies Cutaneous Reactions Neurologic Reactions Eye Disorders Asthenia Alcohol Content The most common adverse reactions across all docetaxel indications are infections, neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, skin reactions, and myalgia. Incidence varies depending on the indication. Adverse reactions are described according to indication.

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. In vivo studies showed that the exposure of docetaxel increased 2.2-fold when it was coadministered with ketoconazole, a potent inhibitor of CYP3A4. Protease inhibitors, particularly ritonavir, may increase the exposure of docetaxel. Concomitant use of docetaxel and drugs that inhibit CYP3A4 may increase exposure to docetaxel and should be avoided. In patients receiving treatment with docetaxel, close monitoring for toxicity and a docetaxel dose reduction could be considered if systemic administration of a potent CYP3A4 inhibitor cannot be avoided. Cytochrome P450 3A4 inducers, inhibitors, or substrates: May alter docetaxel metabolism.

Store between 2°C and 25°C (36°F and 77°F). Freezing does not adversely affect the product. Retain in the original package to protect from light.