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PurposeAlthough current treatment options for metastatic non-small-cell lung cancer (NSCLC) rely on cisplatin-based chemotherapy, individualized approaches to therapy may improve response or reduce unnecessary toxicity. Excision repair cross-complementing 1 (ERCC1) has been associated with cisplatin resistance. We hypothesized that assigning cisplatin based on pretreatment ERCC1 mRNA levels would improve response.Patients and methodsFrom August 2001 to October 2005, 444 stage IV NSCLC patients were enrolled. RNA was isolated from pretreatment biopsies, and quantitative real-time reverse transcriptase PCR assays were performed to determine ERCC1 mRNA expression. Patients were randomly assigned in a 1:2 ratio to either the control or genotypic arm before ERCC1 assessment. Patients in the control arm received docetaxel plus cisplatin. In the genotypic arm, patients with low ERCC1 levels received docetaxel plus cisplatin, and those with high levels received docetaxel plus gemcitabine. The primary end point was the overall objective response rate.ResultsOf 444 patients enrolled, 78 (17.6%) went off study before receiving one cycle of chemotherapy, mainly due to insufficient tumor tissue for ERCC1 mRNA assessment. Of the remaining 346 patients assessable for response, objective response was attained by 53 patients (39.3%) in the control arm and 107 patients (50.7%) in the genotypic arm (P = .02).ConclusionAssessment of ERCC1 mRNA expression in patient tumor tissue is feasible in the clinical setting and predicts response to docetaxel and cisplatin. Additional studies are warranted to optimize methodologies for ERCC1 analysis in small tumor samples and to refine a multibiomarker profile predictive of patient outcome.

Original publication

DOI

10.1200/jco.2006.09.7915

Type

Conference paper

Publication Date

07/2007

Volume

25

Pages

2747 - 2754

Addresses

Hospital Carlos Haya, Malaga, Spain.

Keywords

Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Cisplatin, Endonucleases, DNA-Binding Proteins, Antineoplastic Agents, Treatment Outcome, Drug Resistance, Neoplasm, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Biomarkers, Tumor