A Pharmacokinetic and Pharmacogenetic study of capecitabine in colorectal cancer patients among South Indian population

Abstract

The burden of cancer is increasing worldwide and in Chennai the incidence rate of large bowel cancer is showing a rising trend. Capecitabine is an oral prodrug of 5FU which is approved by FDA for Colorectal cancer Metastatic breast cancer stomach cancer The most common dose limiting adverse effects associated with capecitabine are hyperbilirubinemia diarrhoea hand and foot syndrome myelosupression fatigue and nausea Unpredictable inter individual variability in efficacy and toxicity remain important limitations associated with the use of this anticancer drug Progress in cancer treatment has brought within it challenges that go beyond cure and Toxicities are the biggest hurdles for cancer patients to face Hence this study is undertaken with the aim of identifying the factors such as gender age weight renal and hepatic function and genes that explains variability of toxicity or response of capecitabine in cancer patients Thus through this project the first population pharmacokinetic model was developed for capecitabine in colorectal cancer patients and the potential influence of demographic and genetically controlled factors that could lead to inter patient pharmacokinetic variability among this population was assessed From the study findings it can be concluded that patients with the Dihydro Pyrimidine Dehydrogenase mutation are not good candidates for Capecitabine therapy The therapeutic dose is justifiable with capecitabine treatment as there no effect of the covariates influencing the capecitabine pharmacokinetics in adults newline