BACKGROUND:Platinum-based therapy is pivotal to the treatment of advanced non-small cell lung Cancer (NSCLC). Excision repair cross-complementation group 1 (ERCC1) is a key component of the platinum-DNA repair machinery responsible for nucleotide excision repair. We sought to determine the influence of ERCC1mRNA expression in advanced NSCLC on chemotherapy response, toxicity, and survival after platinum-based chemotherapy. METHODS: Patients randomized to a phase III trial of platinum-based chemotherapy were eligible for inclusion. Formalin-fixed paraffin-embedded tumor biopsies were retrieved for mRNA extraction and purification before quantitative real-time polymerase chain reaction analysis using Taqman technology. Expression data were correlated with treatment response, toxicity, and overall survival. RESULTS:Sixty-six patients were enrolled. No statistically significant relationship existed between ERCC1mRNA expression and response to chemotherapy (p = 0.794) or hematological toxicity. No statistically significant difference in median survival was demonstrated according to ERCC1 expression (high expression, 415 days, 95% confidence interval [95%CI]: 197-633 days; low expression, 327 days [95%CI: 211-433 days]; p = 0.801). High ERCC1mRNA expression was associated with a hazard ratio for death of 0.96 (95% CI 0.919-1.004; p = 0.08). CONCLUSION: In contrast to recent publications, ERCC1mRNA expression in our study did not favor a prognostically better outcome after platinum-based chemotherapy in advanced NSCLC. We explore potential reasons for this, including the need for cautious interpretation of mRNA expression data from archival materials and highlight the need for additional translational research linking gene expression with a promising ERCC1 polymorphism.
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BACKGROUND:Platinum-based therapy is pivotal to the treatment of advanced non-small cell lung Cancer (NSCLC). Excision repair cross-complementation group 1 (ERCC1) is a key component of the platinum-DNA repair machinery responsible for nucleotide excision repair. We sought to determine the influence of ERCC1 mRNA expression in advanced NSCLC on chemotherapy response, toxicity, and survival after platinum-based chemotherapy. METHODS:Patients randomized to a phase III trial of platinum-based chemotherapy were eligible for inclusion. Formalin-fixed paraffin-embedded tumor biopsies were retrieved for mRNA extraction and purification before quantitative real-time polymerase chain reaction analysis using Taqman technology. Expression data were correlated with treatment response, toxicity, and overall survival. RESULTS: Sixty-six patients were enrolled. No statistically significant relationship existed between ERCC1 mRNA expression and response to chemotherapy (p = 0.794) or hematological toxicity. No statistically significant difference in median survival was demonstrated according to ERCC1 expression (high expression, 415 days, 95% confidence interval [95%CI]: 197-633 days; low expression, 327 days [95%CI: 211-433 days]; p = 0.801). High ERCC1 mRNA expression was associated with a hazard ratio for death of 0.96 (95% CI 0.919-1.004; p = 0.08). CONCLUSION: In contrast to recent publications, ERCC1 mRNA expression in our study did not favor a prognostically better outcome after platinum-based chemotherapy in advanced NSCLC. We explore potential reasons for this, including the need for cautious interpretation of mRNA expression data from archival materials and highlight the need for additional translational research linking gene expression with a promising ERCC1 polymorphism.
Authors: Xin Shelley Wang; Qiuling Shi; Charles Lu; Ethan M Basch; Valen E Johnson; Tito R Mendoza; Gary M Mobley; Charles S Cleeland Journal: Cancer Date: 2010-01-01 Impact factor: 6.860