Clinical effects of single nucleotide polymorphisms on drug-related genes in Japanese metastatic renal cell carcinoma patients treated with sunitinib.

Numakura, Kazuyuki; Tsuchiya, Norihiko; Kagaya, Hideaki; Takahashi, Makoto; Tsuruta, Hiroshi; Inoue, Takamitsu; Narita, Shintaro; Huang, Mingguo; Satoh, Shigeru; Niioka, Takenori; Miura, Masatomo; Habuchi, Tomonori

Numakura, Kazuyuki; Tsuchiya, Norihiko; Kagaya, Hideaki; Takahashi, Makoto; Tsuruta, Hiroshi; Inoue, Takamitsu; Narita, Shintaro; Huang, Mingguo; Satoh, Shigeru; Niioka, Takenori; Miura, Masatomo; Habuchi, Tomonori.

Afiliación

Numakura K; aDepartment of Urology, Akita University Graduate School of Medicine bDepartment of Pharmacy cCenter for Kidney Disease and Transplantation, Akita University Hospital, Akita dDepartment of Urology, Yamagata University Graduate School of Medicine, Yamagata, Japan eBrigham and Women's Hospital, Boston, Massachusetts, USA.

Anticancer Drugs ; 28(1): 97-103, 2017 01.

Article en En | MEDLINE | ID: mdl-27564227

RESUMEN

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.

Asunto(s)

Pueblo Asiatico/genética; Carcinoma de Células Renales/genética; Carcinoma de Células Renales/metabolismo; Indoles/farmacocinética; Neoplasias Renales/genética; Neoplasias Renales/metabolismo; Pirroles/farmacocinética; Adulto; Anciano; Anciano de 80 o más Años; Carcinoma de Células Renales/tratamiento farmacológico; Carcinoma de Células Renales/patología; Femenino; Humanos; Indoles/uso terapéutico; Neoplasias Renales/tratamiento farmacológico; Neoplasias Renales/patología; Masculino; Persona de Mediana Edad; Metástasis de la Neoplasia; Polimorfismo de Nucleótido Simple; Pirroles/uso terapéutico; Sunitinib

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirroles / Carcinoma de Células Renales / Pueblo Asiatico / Indoles / Neoplasias Renales Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Anticancer Drugs Asunto de la revista: ANTINEOPLASICOS Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

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