Efficacy versus toxicity of docetaxel in Asian and Caucasian cancer patients from the pharmacogenomics perspectives: a review of the literature

Abstract

Docetaxel is a common anticancer agent in the treatment of breast and lung cancers. Metabolism of docetaxel occurs through cytochrome P450 (CYP) and the function of the enzyme can be altered by genetic, environmental and physiological factors. Interindividual differences in pharmacokinetic profiles of anticancer agents due to changes in CYP function lead to variations in drug efficacy and/or toxicity. Unpredictable toxicities of taxanes have been reported, related to interindividual variability of pharmacokinetics of the drugs. It is evident from multiple studies that adverse events, which are mainly haematological amongst Asian patients receiving docetaxel are higher than as reported in the Caucasian population. Most clinicians who treat Asian patients thus prophylactically support patients with growth factors or reduce the dose of docetaxel. Polymorphisms in genes encoding transporters involved in the uptake of docetaxel will lead to accumulation of the drug in the circulation e.g. ABCB1. Polymorphisms in β‐tubulin (target of docetaxel) affect the taxane chemotherapy results. Presently we have embarked on a project to study the pharmacogenomics of docetaxel in Malaysian breast cancer patients for the very first time to address the above issues. This project is funded by UPM and Al‐Malak Universality, Iraq.