Biblioteca Hospital 12 de Octubre

Single nucleotide polymorphism associations with response and toxic effects in patients with advanced renal-cell carcinoma treated with first-line sunitinib: a multicentre, observational, prospective study (Registro nro. 1125)

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Campo de control de longitud fija 03626na a2200229 4500
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Campo de control H12O
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Campo de control 20180417105935.0
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Campo de control de longitud fija 130622s2011 xxx||||| |||| 00| 0 eng d
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Centro transcriptor H12O
041 ## - CÓDIGO DE LENGUA
Código de lengua del texto/banda sonora o título independiente eng
100 ## - PUNTO DE ACCESO PRINCIPAL - NOMBRE DE PERSONA
Nombre de persona Castellano, Daniel
9 (RLIN) 882
Término indicativo de función Oncología Médica
245 00 - MENCIÓN DE TÍTULO
Título Single nucleotide polymorphism associations with response and toxic effects in patients with advanced renal-cell carcinoma treated with first-line sunitinib: a multicentre, observational, prospective study
Tipo de material [artículo]
260 ## - PUBLICATION, DISTRIBUTION, ETC. (IMPRINT)
Nombre del editor distribuidor etc. Lancet Oncology,
Fecha de publicación distribución etc. 2011.
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Extensión 12(12):1143-1150.
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Nota general Formato Vancouver:
García Donas J, Esteban E, Leandro García LJ, Castellano DE, Del Alba AG, Climent MA, et al. Single nucleotide polymorphism associations with response and toxic effects in patients with advanced renal-cell carcinoma treated with first-line sunitinib: a multicentre, observational, prospective study. Lancet Oncol. 2011;12(12):1143-50.
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Nota de "Con" PMID: 22015057
504 ## - NOTA DE BIBLIOGRAFÍA; ETC.
Nota de bibliografía etc. Contiene 30 referencias
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Sumario etc. BACKGROUND: Sunitinib is a tyrosine kinase inhibitor with proven efficacy in renal-cell carcinoma, but some patients do not respond or need dose reductions due to toxicity. Because there are no validated molecular predictors of response or toxicity to sunitinib, we aimed to identify genetic markers predictive of outcome and toxic effects. METHODS: In our observational, prospective study we enrolled previously untreated adults (≥ 18 years) with clear-cell renal-cell carcinoma at 15 institutions in the Spanish Oncology Genitourinary Group in Spain. Patients received sunitinib according to local practice guidelines. We assessed RECIST response, progression-free survival (PFS), overall survival, and toxicity of sunitinib with 16 key polymorphisms in nine genes: VEGFR2 (rs2305948 and rs1870377), VEGFR3 (rs307826, rs448012, and rs307821), PDGFR-α (rs35597368), VEGF-A (rs2010963, rs699947, and rs1570360), IL8 (rs1126647), CYP3A4 (rs2740574), CYP3A5 (rs776746), ABCB1 (rs1045642, rs1128503, and rs2032582), and ABCB2 (rs2231142). We assessed associations with efficacy and toxicity by use of univariable and multivariable analyses (with clinical factors associated with outcomes as covariates). We adjusted for multiplicity using the Bonferroni method; p values of less than 0·0031 before adjustment were deemed to still be significant after adjustment. FINDINGS: We enrolled 101 patients between Oct 10, 2007, and Dec 13, 2010. 95 of these patients were included in toxicity analyses and 89 in the efficacy analyses. Two VEGFR3 missense polymorphisms were associated with reduced PFS with sunitinib on multivariable analysis: rs307826 (hazard ratio [HR] per allele 3·57, 1·75-7·30; p(unadjusted)=0·00049, p(adjusted)=0·0079) and rs307821 (3·31, 1·64-6·68; p(unadjusted)=0·00085, p(adjusted)=0·014). The CYP3A5*1 (rs776746) high metabolising allele was associated in a multivariable analysis with an increased risk of dose reductions due to toxicity (HR per allele 3·75, 1·67-8·41; p(unadjusted)=0·0014, p(adjusted)=0·022). No other SNPs were associated with sunitinib response or toxicity. INTERPRETATION: Polymorphisms in VEGFR3 and CYP3A5*1 might be able to define a subset of patients with renal-cell carcinoma with decreased sunitinib response and tolerability. If confirmed, these results should promote interventional studies testing alternative therapeutic approaches for patients with such variants.
710 ## - PUNTO DE ACCESO ADICIONAL - NOMBRE DE ENTIDAD
9 (RLIN) 303
Nombre de entidad o nombre de jurisdicción como elemento inicial Servicio de Oncología Médica
856 ## - LOCALIZACIÓN Y ACCESO ELECTRÓNICOS
Identificador Uniforme del Recurso (URI) http://pc-h12o-es.m-hdoct.a17.csinet.es/pdf/pc/1/pc1125.pdf
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          Hospital Universitario 12 de Octubre Hospital Universitario 12 de Octubre 2015-10-23 PC1125 2015-10-23 2015-10-23 Artículo

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