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BackgroundPlatinum-based doublets are the standard chemotherapy for advanced non-small-cell lung cancer (NSCLC). Excision-repair cross-complementing 1 (ERCC1), xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunit M1 (RRM1) are essential to the repair of cisplatin DNA adducts. Multidrug resistance 1 (MDR1) has been related to antimicrotubule resistance. We assessed whether single nucleotide polymorphisms (SNPs) in ERCC1, XPD, RRM1 and MDR1, and ERCC1 mRNA expression, predicted survival in docetaxel-cisplatin-treated stage IV NSCLC patients.Patients and methodsUsing the TaqMan 5' nuclease assay, we examined ERCC1 118, XPD 751 and 312, RRM1 -37C/A, and MDR1 C3435T SNPs in peripheral blood lymphocytes (PBLs) obtained from 62 docetaxel-cisplatin-treated advanced NSCLC patients. ERCC1 expression was measured in RNA isolated from PBLs using real-time reverse transcriptase PCR.ResultsOverall median survival was 10.26 months. Median survival was 9.67 months for 34 patients with ERCC1 118 C/T, 9.74 months for 17 patients with T/T, and not reached for 11 patients with C/C (P=0.04). Similar significant differences in time to progression were observed according to ERCC1 118 genotype (P=0.03). No other significant differences were observed.ConclusionsPatients homozygous for the ERCC1 118 C allele demonstrated a significantly better survival. ERCC1 SNP assessment could be an important component of tailored chemotherapy trials.

Original publication

DOI

10.1093/annonc/mdh319

Type

Conference paper

Publication Date

08/2004

Volume

15

Pages

1194 - 1203

Addresses

Hospital Clinico Lozano Blesa, Zaragoza, Spain.

Keywords

Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Cisplatin, Taxoids, Endonucleases, DNA-Binding Proteins, DNA Adducts, Antineoplastic Combined Chemotherapy Protocols, Prognosis, Treatment Outcome, Survival Analysis, Reverse Transcriptase Polymerase Chain Reaction, DNA Repair, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, Female, Male, Docetaxel