MP69-03 CLINICAL OUTCOME OF SINGLE NUCLEOTIDE POLYMORPHISMS ON PHARMACOKINETIC GENES IN JAPANESE METASTATIC RENAL CELL CARCINOMA PATIENTS TREATED WITH SUNITINIB

Abstract

You have accessJournal of UrologyKidney Cancer: Advanced II1 Apr 2015MP69-03 CLINICAL OUTCOME OF SINGLE NUCLEOTIDE POLYMORPHISMS ON PHARMACOKINETIC GENES IN JAPANESE METASTATIC RENAL CELL CARCINOMA PATIENTS TREATED WITH SUNITINIB Kazuyuki Numakura, Norihiko Tsuchiya, Makoto Takahashi, Hiroshi Tsuruta, Susumu Akihama, Mitsuru Saito, Tkamitsu Inoue, Shintaro Narita, Mingguo Huang, Shigeru Satoh, and Tomonori Habuchi Kazuyuki NumakuraKazuyuki Numakura More articles by this author , Norihiko TsuchiyaNorihiko Tsuchiya More articles by this author , Makoto TakahashiMakoto Takahashi More articles by this author , Hiroshi TsurutaHiroshi Tsuruta More articles by this author , Susumu AkihamaSusumu Akihama More articles by this author , Mitsuru SaitoMitsuru Saito More articles by this author , Tkamitsu InoueTkamitsu Inoue More articles by this author , Shintaro NaritaShintaro Narita More articles by this author , Mingguo HuangMingguo Huang More articles by this author , Shigeru SatohShigeru Satoh More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2507AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Sunitinib is a multi-targeted tyrosine kinase inhibitor for patients with metastatic renal cell carcinoma (mRCC). Its therapeutic efficacy and toxicity manifested with a wide heterogeneity and are difficult to predict before treatment initiation. To evaluate predictors of clinical outcomes (progression-free survival (PFS), overall survival (OS), and adverse events (AEs)) in mRCC patients treated with sunitinib, we analyzed single nucleotide polymorphisms (SNPs) in the pharmacokinetic genes of sunitinib in Japanese population. METHODS This study included 70 mRCC patients treated with sunitinib between April 2006 and July 2013. We assessed baseline clinical factors and examined 7 genetic polymorphisms in 4 candidate genes involved in sunitinib pharmacokinetics, which were located in genes encoding its transport: ABCB1 (rs1045642, rs1128503, rs2032582 and rs7779562) and ABCG2 (rs2231142), and metabolism: CYP3A4 (rs35599367) and CYP3A5 (rs776746). Associations between SNPs and clinical outcomes were analyzed. RESULTS Sixty four patients were successfully genotyped all seven SNPs. For each seven SNPs, no significant association was observed between certain genotypes and PFS and OS. The incidence of hypertension and hand-foot syndrome and the risk of multiple AEs were significantly higher in patients carrying ABCB1 rs2032582 GG genotype (OR 2.06, 95% CI 1.019–3.363, p = 0.02; OR 1.04, 95% CI 1.002–1.352, p = 0.04, R 3.29; 95% CI 1.207–4.777; p = 0.02, respectively) compared to those carrying variant alleles. Multiple AEs was also significantly observed in variant homozygote CC of ABCB1 rs7779562 polymorphism (OR 3.95; 95% CI 1.60–5.32; p = 0.046) compared to those with at least one wild type G allele. CONCLUSIONS In Japanese mRCC patients, carrying the rs2032582 GG genotype or the rs7779562 CC genotype in ABCB1 are associated with individual susceptibility to AEs of sunitinib. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e867 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kazuyuki Numakura More articles by this author Norihiko Tsuchiya More articles by this author Makoto Takahashi More articles by this author Hiroshi Tsuruta More articles by this author Susumu Akihama More articles by this author Mitsuru Saito More articles by this author Tkamitsu Inoue More articles by this author Shintaro Narita More articles by this author Mingguo Huang More articles by this author Shigeru Satoh More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...