The Tradition of the Rising Sun: When Geography Counts

Ethnic differences in the pharmacokinetics and tolerability of anticancer drugs, especially between Asian and white patients, have been extensively reported. Allelic variants of genes encoding drug-metabolizing enzymes are expressed with different incidences in different ethnic groups.1 Irinotecan is more active in Asian than in white patients because of the single-nucleotide polymorphisms of UDP glucuronosyltransferase gene (UGT1A1), which is responsible for the irinotecan metabolism. Differences in the cellular processing of irinotecan may result in differences in toxicity, compliance, and chemosensitivity.2 Thymidylate synthase (TS) is an important target for cytotoxic drugs such as 5-fluorouracil and its oral prodrugs, including uracil/tegafur (UFT). Ethnic variation in a TS gene regulatory element have been identified and may have influence on pyrimidine homeostasis and drug therapy.3 Treatment with oral UFT produces stable effective serum concentrations of 5-fluorouracil for a prolonged period of time. Although UFT has a minimal direct antitumor effect, it has been shown to be therapeutically useful against several tumors, including NSCLC.