The influence of platinum pathway polymorphisms on the outcome in patients with malignant mesothelioma.

Erculj, N; Kovac, V; Hmeljak, J; Dolzan, V

Erculj, N; Kovac, V; Hmeljak, J; Dolzan, V.

Afiliación

Erculj N; Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.

Ann Oncol ; 23(4): 961-7, 2012 Apr.

Article en En | MEDLINE | ID: mdl-21765044

RESUMEN

BACKGROUND: Platinum-based therapy is widely used in the treatment of malignant mesothelioma (MM); however, the efficacy and toxicity of platinum agents vary greatly between patients. The aim of our study was to evaluate the influence of platinum pathway polymorphisms on treatment outcome in patients with MM. PATIENTS AND METHODS: In total, 133 patients with MM treated with (n = 97) or without (n = 36) platinum-based therapy were genotyped for common XPD, ERCC1, and GSTP1 polymorphisms, as well as for GSTM1 and GSTT1 gene deletion. Haplotype analysis was carried out to assess the combined effect of nucleotide excision repair (NER) polymorphisms. RESULTS: GST polymorphisms were not associated with treatment outcome in patients with MM. In the group of platinum-treated patients with MM, ERCC1 8092C/C wild-type genotype significantly influenced progression-free survival (PFS) in multivariable analysis accounting for clinical variables (P = 0.034). XPD 312Asp/Asp and ERCC1 8092C/C wild-type genotypes also increased the odds of treatment-related toxic effects in univariable as well as multivariable analysis. The association of wild-type NER genotypes with better PFS and higher susceptibility to treatment-related toxic effects was confirmed in haplotype analysis. CONCLUSIONS: Our results suggest that polymorphisms in NER pathway influence platinum-treatment efficacy and toxicity; therefore, these should be further evaluated as potential markers for the prediction of clinical outcome in patients with MM.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico; Mesotelioma/tratamiento farmacológico; Adulto; Anciano; Anciano de 80 o más Años; Alopecia/inducido químicamente; Alopecia/genética; Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos; Carboplatino/administración & dosificación; Cisplatino/administración & dosificación; Reparación del ADN/genética; Proteínas de Unión al ADN/genética; Supervivencia sin Enfermedad; Endonucleasas/genética; Femenino; Estudios de Asociación Genética; Glutatión Transferasa/genética; Haplotipos; Humanos; Leucopenia/inducido químicamente; Leucopenia/genética; Masculino; Mesotelioma/genética; Mesotelioma/mortalidad; Persona de Mediana Edad; Náusea/inducido químicamente; Náusea/genética; Polimorfismo Genético; Modelos de Riesgos Proporcionales; Análisis de Secuencia de ADN; Trombocitopenia/inducido químicamente; Trombocitopenia/genética; Resultado del Tratamiento; Proteína de la Xerodermia Pigmentosa del Grupo D/genética

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Mesotelioma Tipo de estudio: Prognostic_studies Límite: Aged80 Idioma: En Revista: Ann Oncol Asunto de la revista: NEOPLASIAS Año: 2012 Tipo del documento: Article País de afiliación: Eslovenia Pais de publicación: Reino Unido

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