Although
sunitinib is a well-established chemotherapeutic for metastatic
renal cell carcinoma (mRCC), there are no robust markers that predict efficacy and toxicity. We analyzed the effect of single nucleotide polymorphisms (SNPs) in genes involved in
sunitinib pharmacokinetics on clinical outcomes in Japanese patients with mRCC. We analyzed the effect of SNPs in genes involved in
sunitinib pharmacokinetics on the clinical outcome in mRCC patients in a Japanese population. We evaluated seven SNPs in four candidate genes, the
transport proteins ATP-binding cassette (ABC) B1 (rs1045642, rs1128503, rs2032582, and rs7779562) and ABCG2 (rs2231142), and the metabolic
proteins cytochrome P450 (CYP) 3A4 (rs35599367) and
CYP3A5 (rs776746) in 70 patients. No significant association was observed between the genotypes of each SNP and time to
dose reduction, progression-free survival, overall survival, and best objective response. Meanwhile, the incidence of grade 2 or greater
hypertension and
hand-foot syndrome, and multiple adverse events (>3), was significantly higher in patients carrying the ABCB1 rs2032582 GG genotype [odds ratio (OR): 5.37, 95% confidence interval (CI) 1.02-14.63, P=0.035; OR: 3.17, 95% CI 1.06-9.52, P=0.036, OR: 3.35; 95% CI 1.14-9.84; P=0.025, respectively]. In conclusion, our data showed that the ABCB1 rs2032582 GG genotype was associated with individual adverse events' susceptibility among Japanese patients treated with
sunitinib in routine clinical settings.