Multidrug and toxin extrusion 1 and human organic cation transporter 1 polymorphisms in patients with castration-resistant prostate cancer receiving metformin (SAKK 08/09)

摘要: This study was initiated to explore the impact of organic cation transporter 1 (OCT1) and multidrug toxin extrusion (MATE1) genetic polymorphisms on toxicity, clinical activity metformin in patients with castration-resistant prostate cancer (CRPC). The SAKK 08/09 trial included 44 CRPC receive single-agent 1000 mg two times a day until disease progression or unwanted toxicity. Drug pathway-associated gene OCT1 (rs622342) MATE1 (rs2289669) were assessed. primary objective this define relationship between mutations OCT1, progression-free survival (PFS) at 12 weeks absolute PFS PSA response consenting 08/09. secondary analyze association MATE1, metformin-related overall survival. Thirty-six evaluable for pharmacogenetic analysis. Homozygous carriers polymorphic C-allele had no toxicity as compared 41.9% any least one wild-type A-allele (P=0.07). Disease according RECIST (Response Evaluation Criteria In Solid Tumors) significantly more frequent homozygous (80%) (28.6%) (P=0.002). also (44%) G-allele (12.5%) not associated PFS. has been shown be less higher risk tumor receiving an anticancer treatment. Polymorphisms drug transporters are attractive molecular markers serve potential predictors efficacy future studies.