Pharmacogenetics of paclitaxel metabolism

Crit Rev Oncol Hematol. 2007 Mar;61(3):222-9. doi: 10.1016/j.critrevonc.2006.09.006. Epub 2006 Nov 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Aryl Hydrocarbon Hydroxylases / drug effects
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Cytochrome P-450 CYP2C8
  • Cytochrome P-450 Enzyme System / drug effects*
  • Cytochrome P-450 Enzyme System / genetics
  • Humans
  • Paclitaxel / pharmacokinetics*
  • Paclitaxel / pharmacology
  • Polymorphism, Genetic

Substances

  • Antineoplastic Agents, Phytogenic
  • Cytochrome P-450 Enzyme System
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C8 protein, human
  • Cytochrome P-450 CYP2C8
  • Paclitaxel