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

Autor: T Takahashi, A Yokoyama, N. Yamamoto, Yuichiro Takeda, Kenji Eguchi, Takashi Ogura, Koshiro Watanabe, Hiroshi Isobe, Noriyuki Masuda, Hiroshi Kunikane, M Shibuya
Rok vydání: 2008
Předmět:
Zdroj: Clinical Pharmacology & Therapeutics. 85:149-154
ISSN: 1532-6535
0009-9236
DOI: 10.1038/clpt.2008.152
Popis: 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
Databáze: OpenAIRE
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