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 |
003 - IDENTIFICADOR DEL NÚMERO DE CONTROL | |
Campo de control | H12O |
005 - FECHA Y HORA DE LA ÚLTIMA TRANSACCIÓN | |
Campo de control | 20180417105935.0 |
008 - CÓDIGOS DE INFORMACIÓN DE LONGITUD FIJA | |
Campo de control de longitud fija | 130622s2011 xxx||||| |||| 00| 0 eng d |
040 ## - FUENTE DE LA CATALOGACIÓN | |
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. |
300 ## - DESCRIPCIÓN FÍSICA | |
Extensión | 12(12):1143-1150. |
500 ## - NOTA GENERAL | |
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. |
501 ## - NOTA DE “CON” | |
Nota de "Con" | PMID: 22015057 |
504 ## - NOTA DE BIBLIOGRAFÍA; ETC. | |
Nota de bibliografía etc. | Contiene 30 referencias |
520 ## - NOTA DE SUMARIO; ETC. | |
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 |
Acceso | Solicitar documento |
942 ## - ENTRADA PARA ELEMENTOS AGREGADOS (KOHA) | |
Suprimido en OPAC | Público |
Fuente de clasificación o esquema de ordenación en estanterías | |
Koha [por defecto] tipo de item | Artículo |
Suprimido | Estado de pérdida | Fuente de clasificación o esquema de ordenación en estanterías | Estropeado | No para préstamo | Localización permanente | Localización actual | Fecha de adquisición | Signatura completa | Fecha última consulta | Fecha del precio de reemplazo | Tipo de item de Koha |
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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 |