Pharmacogenetics of irinotecan: An ethnicity-based prediction of irinotecan adverse events.

Irinotecan is now regarded as the most active drug for the treatment of colorectal cancer. However, one of the most difficult issues oncologists face is deciding the optimal dose for an individual patient, as each individual shows different outcomes even at the same dose with regard to treatment related adverse events, ranging from no toxicity to a lethal event. Inherited genetic polymorphism of a single gene or multiple genes (haplotype or linkage disequilibrium) involved in SN-38 glucuronidation, a predominant route of irinotecan detoxification, is now recognized as a significant factor that can alter the incidence of side effects. Attempts to explore such inherited genetic variability have been focused on elucidating interindividual as well as interethnic differences. Genotyping studies in relation to adverse events in an individual or in a group of similar ethnicity should contribute to establishing individual-oriented or ethnicity-oriented irinotecan treatment regimens. This review highlights current single- or multi-tired approaches for the elucidation of genetic predispositions of patients to severe toxicities, especially among Asians. The purpose of this is to contribute to minimizing toxicity by dose modifications, with the consequent aim of maximizing dose intensity and efficacy, an ultimate goal of irinotecan-individualized therapy.