Phase I/II Pharmacokinetic and Pharmacogenomic Study of UGT1A1 Polymorphism in Elderly Patients With Advanced Non–Small Cell Lung Cancer Treated With Irinotecan

This phase II study investigated the recommended dose (RD) of irinotecan (CPT‐11) by dose escalation in elderly (≥70 years) chemotherapy‐naive Japanese patients with advanced non–small cell lung cancer. UGT1A1*28 and *6 polymorphisms and pharmacokinetics were also investigated. Thirty‐seven patients received the RD, 100 mg/m2 of intravenous CPT‐11, on days 1 and 8 of each 3‐week cycle in phase II. The overall response rate was 8.1%. The median survival time was 441 days, and time to progression was 132 days. A significant correlation was observed between the incidence of grade 3/4 neutropenia and area under the time‐concentration curve (AUC) values of SN‐38. A reduction in AUC ratios (AUCSN‐38G/AUCSN‐38) and a rise in incidence of grade 3/4 neutropenia were observed with increase in polymorphism. The regimen was well tolerated and provided good disease control and promising survival effects. An analysis of the influence of UGT1A1*28 and *6 polymorphisms provides useful information for the prediction of CPT‐11‐related hematological toxicity. Clinical Pharmacology & Therapeutics (2009); 85, 2, 149–154 doi:10.1038/clpt.2008.152