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PurposeNew therapeutic approaches are being developed based on findings that several genetic abnormalities underlying non-small-cell lung cancer (NSCLC) can influence chemosensitivity. The identification of molecular markers, useful for therapeutic decisions in lung cancer, is thus crucial for disease management. The present study evaluated single-nucleotide polymorphisms (SNPs) in XRCC3, XPD and Aurora kinase A in NSCLC patients in order to assess whether these biomarkers were able to predict the outcomes of the patients.MethodsThe Spanish Lung Cancer Group prospectively assessed this clinical study. Eligible patients had histologically confirmed stage IV or IIIB (with malignant pleural effusion) NSCLC, which had not previously been treated with chemotherapy, and a World Health Organization performance status (PS) of 0-1. Patients received intravenous doses of vinorelbine 25 mg/m(2) on days 1 and 8, and cisplatin 75 mg/m(2) on day 1, every 21 days for a maximum of 6 cycles. Venous blood was collected from each, and genomic DNA was isolated. SNPs in XRCC3 T241M, XPD K751Q, XPD D312N, AURORA 91, AURORA 169 were assessed.ResultsThe study included 180 patients. Median age was 62 years; 87 % were male; 34 % had PS 0; and 83 % had stage IV disease. The median number of cycles was 4. Time to progression was 5.1 months (95 % CI, 4.2-5.9). Overall median survival was 8.6 months (95 % CI, 7.1-10.1). There was no significant association between SNPs in XRCC3 T241M, XPD K751Q, XPD D312N, AURORA 91, AURORA 169 in outcome or toxicity.ConclusionsOur findings indicate that SNPs in XRCC3, XPD or Aurora kinase A cannot predict outcomes in advanced NSCLC patients treated with platinum-based chemotherapy.

Original publication

DOI

10.1007/s00280-012-1985-9

Type

Journal article

Journal

Cancer chemotherapy and pharmacology

Publication Date

12/2012

Volume

70

Pages

883 - 890

Addresses

Servicio de Oncología Médica, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain. mprovencio.hpth@salud.madrid.org

Keywords

Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Cisplatin, Vinblastine, Protein-Serine-Threonine Kinases, DNA-Binding Proteins, Antineoplastic Combined Chemotherapy Protocols, Disease-Free Survival, Drug Administration Schedule, Prospective Studies, Genotype, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, Spain, Female, Male, Xeroderma Pigmentosum Group D Protein, Aurora Kinase A, Aurora Kinases, Vinorelbine