Docetaxel

Indications

Docetaxel is used for: Breast cancer, Lung cancer, Prostate cancer, Stomach cancer, Head/neck cancer

Adult Dose

Intravenous Breast cancer Adult: 60-100 mg/m2 by infusion over 1 hr once every 3 wk. In combination w/ doxorubicin or capecitabine or as adjuvant therapy w/ doxorubicin and cyclophosphamide: 75 mg/m2 once every 3 wk. In combination w/ trastuzumab: 100 mg/m2 once every 3 wk. Hepatic impairment: Mild to moderate: Reduce dose from 100 mg/m2 to 75 mg/m2. Severe: Avoid use. Intravenous Head and neck cancer; Prostate cancer ; Non-small cell lung cancer; Gastric adenocarcinoma Adult: 75 mg/m2 by infusion over 1 hr once every 3 wk. For gastric adenocarcinoma: Dose is given before cisplatin and fluorouracil. For head and neck cancer: Given before cisplatin and fluorouracil for 3 cycles followed by chemoradiotherapy or 4 wk followed by radiotherapy alone. For prostate cancer: May be given w/ oral prednisolone 5 mg bid continuously during treatment.

Child Dose

Renal Dose

Renal Impairment Dose adjustment not necessary

Administration

IV Preparation Dual vial formulation Requires 2-step dilution Reconstitute vial contents (20 mg/0.5 mL or 80 mg/2 mL) with supplied diluent (13% (w/w) ethanol/water) to obtain a 10 mg/mL solution Further dilute with NS or D5W to a final concentration of 0.3-0.74 mg/mL and prepare in a glass bottle, polypropylene, or polyolefin plastic bag to prevent leaching of plasticizers Use within 4 hr (including the 1 hr infusion) Single vial formulation Requires 1-step dilution Available as 20 mg/mL solution; further dilute with NS or D5W to a final concentration of 0.3-0.74 mg/mL and prepare in a glass bottle, polypropylene, or polyolefin plastic bag to prevent leaching of plasticizers Use within 4 hr (including the 1 hr infusion) IV Administration Anaphylactoid-like reactions have been reported: premedicate with dexamethasone (Breast CA, NSCLC: 8 mg PO q12hr for 3 days starting 1 day prior to administration of docetaxel; Prostate CA: 8 mg PO at 12 hr-, 3 hr- and 1 hr preinfusion) Infuse over 1 hr When administered as sequential infusions, taxane derivatives should be administered before platinum derivatives (cisplatin, carboplatin) to limit myelosuppression and to enhance efficacy

Contra Indications

Previous severe hypersensitivity reaction to docetaxel, the solvent or polysorbate 80. Severe neutropenia; pregnancy, severe liver impairment.

Precautions

Lactation. Hepatic impairment. Monitor liver blood function and blood counts regularly. Premedication with oral dexamethsaone at 16 mg daily for 3 days, starting one day before docetaxel treatment is recommended. Lactation: Not known if excreted in breast milk, do not nurse

Pregnancy-Lactation

Pregnancy Based on findings in animal reproduction studies and its mechanism of action, therapy can cause fetal harm when administered to a pregnant woman; limited available human data are not sufficient to inform drug-associated risk during pregnancy Verify the pregnancy status of females of reproductive potential prior to initiating therapy Contraception Females of reproductive potential: Use effective contraception during treatment and for 6 months following last dose Males with female partners of reproductive potential: Use effective contraception during treatment and for 3 months following last dose Infertility Based on findings in animal studies, therapy may impair fertility in males of reproductive potential Lactation There is no information regarding presence of docetaxel in human milk, or effects on milk production or the breast-fed child; no lactation studies in animals have been conducted; because of potential for serious adverse reactions in a breast-fed child from docetaxel exposure, including toxic death, hepatotoxicity, neutropenia, and acute myeloid leukemia, advise women not to breastfeed during treatment and for 2 weeks after last dose

Interactions

CYP3A4 inducers, inhibitors, or substrates may alter docetaxel metabolism.

Adverse Effects

Side effects of Docetaxel : >50% Alopecia, Anemia, Leukopenia, Neutropenia, Asthenia 10-50% Fever, Infections, Fluid retention, Hypersensitivity, Skin reactions, Diarrhea, Nausea, Vomiting, Sensory neuropathy, Myalgia, Nail changes 1-10% Arthralgia, Thrombocytopenia Potentially Fatal: Neutropenia; fluid retention syndrome; anaemia.

Mechanism of Action

Docetaxel disrupts the microtubular network in cells that is essential for vital mitotic and interphase cellular functions. It binds to the free tubulin and promotes the assembly of tubulin into stable microtubules while simultaneously inhibiting their disassembly, resulting in inhibition of mitosis.