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- Title
Phase I/II Pharmacokinetic and Pharmacogenomic Study of UGT1A1 Polymorphism in Elderly Patients With Advanced Non–Small Cell Lung Cancer Treated With Irinotecan.
- Authors
Yamamoto, N.; Takahashi, T.; Kunikane, H.; Masuda, N.; Eguchi, K.; Shibuya, M.; Takeda, Y.; Isobe, H.; Ogura, T.; Yokoyama, A.; Watanabe, K.
- 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/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
- Subjects
DRUG therapy; LUNG cancer; GENETIC polymorphisms; PHARMACOKINETICS; NEUTROPENIA; PHARMACOLOGY; HEMATOLOGICAL oncology
- Publication
Clinical Pharmacology & Therapeutics, 2009, Vol 85, Issue 2, p149
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1038/clpt.2008.152