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

Prostate Cancer and Prostatic Diseases
M JoergerChristian Rothermundt

Abstract

This study was initiated to explore the impact of organic cation transporter 1 (OCT1) and multidrug and toxin extrusion transporter 1 (MATE1) genetic polymorphisms on toxicity, and clinical activity of metformin in patients with castration-resistant prostate cancer (CRPC). The SAKK 08/09 trial included 44 patients with CRPC to receive single-agent metformin 1000 mg two times a day until disease progression or unwanted toxicity. Drug pathway-associated gene polymorphisms of OCT1 (rs622342) and MATE1 (rs2289669) were assessed. The primary objective of this study was to define the relationship between mutations in OCT1, MATE1 and progression-free survival (PFS) at 12 weeks absolute PFS and PSA response in consenting patients of SAKK 08/09. The secondary objective of this study was to analyze the association between mutations in OCT1, MATE1, metformin-related toxicity, PSA response at 12 weeks and overall survival. Thirty-six patients were evaluable for pharmacogenetic analysis. Homozygous carriers of the polymorphic OCT1 C-allele had no metformin-related toxicity as compared with 41.9% for any metformin-related toxicity in carriers of at least one wild-type A-allele (P=0.07). Disease progression according to RECIST (Response Evalu...Continue Reading

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Citations

Dec 6, 2018·Diabetes/metabolism Research and Reviews·Gaia Chiara ManninoGiorgio Sesti
Dec 3, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Benjamin D HopkinsLewis C Cantley

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