When used with anticonvulsants, which induce CYP3A4, an increased dose of docetaxel may be required.Pre-treatment with corticosteroids has been used to decrease hypersensitivity reactions and oedema in response to docetaxel and has shown no effect on the pharmacokinetics of docetaxel. The efficacy of docetaxel was improved by treatment with oral capecitabine, and after more than 27 months follow-up the survival benefit has been confirmed. Doxorubicin was combined with docetaxel in one study of 24 patients and resulted in an increased AUC of docetaxel by 50 to 70%, indicating doxorubicin may affect the disposition of docetaxel. Etoposide has also been shown to decrease docetaxel clearance, though patient numbers for this observation have been low.Prednisone given with docetaxel led to improved survival, quality of life and pain management in patients with hormone-refractory prostate cancer. Chemistry
Docetaxel is of the chemotherapy drug class; taxane, and is a semi-synthetic analogue of paclitaxel (Taxol), an extract from the bark of the rare Pacific yew tree, Taxus brevifolia. Due to scarcity of paclitaxel, extensive research was carried out leading to the formulation of docetaxel – an esterified product of 10-deacetyl baccatin III, which is extracted from the renewable and more readily available leaves of the European yew tree. Docetaxel differs from paclitaxel at two positions in its chemical structure. It has a hydroxyl functional group on carbon 10, whereas paclitaxel has an acetate ester, and a tert-butyl carbamate ester exists on the phenylpropionate side chain instead of the benzamide in paclitaxel.
Contraindications and patient factors
Docetaxel is contraindicated for use with patients with a baseline neutrophil count less than 1500 cells/µL, a history of severe hypersensitivity reactions to docetaxel or polysorbate 80, severe liver impairment and pregnant or breast-feeding women.Side effects are experienced more frequently by patients of 65 years or older, but dosage is usually not decreased. Kidney failure is thought not to be a significant factor for docetaxel dosage adjustment. Patients with hepatic insufficiency resulting in serum bilirubin greater than the upper limit of normal (ULN) should not be administered docetaxel, though this is not a stated contraindication. Dosage should be reduced by 20% in people who develop grade 3 or 4 diarrhea following exposure to docetaxel, hepatotoxicity defined by liver enzymes at levels greater than five times the ULN, and grade 2 palmer-planter toxicity.Paediatric trials of docetaxel have been limited, and so safety of use in patients under 16 years has not been established. Pregnancy
Based on the limited data available, docetaxel appears to be safe in pregnancy if administered during the second and third trimesters; however, maternal and fetal risks should be weighed against benefits to determine the appropriate course of action. As with all chemotherapeutic agents, docetaxel administered to pregnant animals causes a variety of embryofetal toxicities, including death, when given during the period of organogenesis. Yet adequate studies investigating maternal and fetal effects in humans are lacking.