Pharmacogenetics of paclitaxel metabolism.
Paclitaxel is one of the most widely used and effective anticancer drugs. Paclitaxel's clinical utility spans many tumor sites, including treatment of ovarian, breast, lung, head and neck, and unknown primary cancers. As is the case with most chemotherapy drugs, paclitaxel is administered empirically with little individualization of dose other than adjustment for body surface area. Metabolism of the drug is predominantly by the liver by cytochromes P450 2C8 and 3A4. Recent evidence points to the presence of polymorphisms in these enzymes. The clinical relevance of these polymorphisms is not yet fully explored, though they are expected to be key in fulfilling the ultimate goal of individualized dosing of paclitaxel. Here we review the pharmacology of paclitaxel and consider the possible effects pharmacogenetics may have on paclitaxel therapy.
Spratlin
Jennifer
J
Cross Cancer Institute, Department of Medical Oncology, University of Alberta, Edmonton, Alberta, Canada.
Sawyer
Michael B
MB
D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics* / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases / Q000187:drug effects / Q000235:genetics; D065727:Cytochrome P-450 CYP2C8; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D017239:Paclitaxel / Q000493:pharmacokinetics* / Q000494:pharmacology; D011110:Polymorphism, Genetic
D000972:Antineoplastic Agents, Phytogenic; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; D017239:Paclitaxel