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.
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.
Han
Ji-Youn
JY
Research Institute and Hospital, National Cancer Center, Goyang, Korea. jymama@ncc.re.kr
Lim
Hyeong-Seok
HS
Shin
Eun Soon
ES
Yoo
Yeon-Kyeong
YK
Park
Yong Hoon
YH
Lee
Jong-Eun
JE
Kim
Heung Tae
HT
Lee
Jin Soo
JS
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
D000972:Antineoplastic Agents, Phytogenic; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human; D000077146:Irinotecan; D002166:Camptothecin