Article ID Journal Published Year Pages File Type
2143570 Lung Cancer 2008 7 Pages PDF
Abstract

SummaryTo investigate whether the OATP1B1 polymorphisms affect irinotecan-pharmacokinetics and subsequent toxicity and tumor response of patients with advanced NSCLC. A total of 81 Korean NSCLC patients enrolled in a phase II study of irinotecan and cisplatin chemotherapy were genotyped for OATP1B1 −11187G>A, 388A>G and 521T>C variants. The 521TC or CC and −11187AA genotypes were associated with higher AUCSN-38 (p = 0.016 and 0.030, respectively). When haplotypes were assigned, patients with *15 haplotype showed significantly higher AUCSN-38 than *1a or *1b haplotypes (p = 0.006). Grade 4 neutropenia was associated with the 521TC or CC genotypes, whereas, grade 3 diarrhea was associated with 388GG genotype (p = 0.046). Of the 81 patients enrolled, 77 were assessable for response and 36 (47%) patients achieved partial responses (PR). However, no statistical significance was observed between genotype and response. These findings suggest that OATP1B1 variants are involved in SN-38 disposition and highly predictive for severe toxicity of NSCLC patients treated with irinotecan-based chemotherapy.

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