title: Influence of the organic anion-transporting polypeptide 1B1 (OATP1B1) polymorphisms on irinotecan-pharmacokinetics and clinical outcome of patients with advanced non-small cell lung cancer.
abstract: To 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 AUC(SN-38) (p=0.016 and 0.030, respectively). When haplotypes were assigned, patients with *15 haplotype showed significantly higher AUC(SN-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.
authors.affiliation: Research Institute and Hospital, National Cancer Center, Goyang, Korea. jymama@ncc.re.kr
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Han
authors.forename: Hyeong-Seok
authors.initials: HS
authors.lastname: Lim
authors.forename: Eun Soon
authors.initials: ES
authors.lastname: Shin
authors.forename: Yeon-Kyeong
authors.initials: YK
authors.lastname: Yoo
authors.forename: Yong Hoon
authors.initials: YH
authors.lastname: Park
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Heung Tae
authors.initials: HT
authors.lastname: Kim
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D000077146:Irinotecan; D027381:Liver-Specific Organic Anion Transporter 1; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000235:genetics*; D011110:Polymorphism, Genetic; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human; D000077146:Irinotecan; D002166:Camptothecin