학술논문
Phase I/II Pharmacokinetic and Pharmacogenomic Study of UGT1A1 Polymorphism in Elderly Patients With Advanced Non-Small Cell Lung Cancer Treated With Irinotecan
Document Type
Academic Journal
Author
Source
Clinical Pharmacology & Therapeutics. Feb 01, 2009 85(2):149-154
Subject
Language
English
ISSN
0009-9236
Abstract
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/m 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.