Clinical research of individualized therapy in advanced non-small cell lung cancer guiding by detection of ERCC1 protein

Background and purpose: Excision repair cross-complementing 1(ERCC1) has been associated with cisplatin resistance.The study aimed to explore the role and clinical significance of detection of ERCC1 protein in individualized therapy of advanced non-small cell lung cancer(NSCLC) patients.Methods: From Aug.2006 to Jul.2009,222 stage ⅢB/Ⅳ NSCLC patients were enrolled.The expressions of ERCC1 protein in advanced stage NSCLC tissues were qualitatively detected by immunohistochemical methods.Patients were randomly assigned in a 2∶1 ratio to either the individualized treatment group or the standard treatment group before ERCC1 assessment.Patients in the control arm received gemcitabine plus cisplatin or vinorelbine plus cisplatin.In the genotypic arm,patients with low ERCC1 levels received gemcitabine plus cisplatin or vinorelbine plus cisplatin,and those with high levels received gemcitabine plus vinorelbine.Main outcome measures include response rate,overall survival and time to progression.Differences between the groups were statistically analyzed by chi-square test.Survival differences were analyzed by temporal inspection and Kaplan-Meier survival curves.Results: Follow-up data was up to Sep.30,2012.Objective response was obtained by 20 patients(26.6%) in the standard treatment group and 40 patients(27.2%) in the individualized treatment group(P=0.931).One year survival rate was 40.0% in the standard treatment group and 48.3% in the genotypic arm(P=0.24).The median survival time was 10.2 months(95%CI was 8.67 months to 11.73 months) in the standard treatment group and 13.3 months(95%CI was 12.46 months to 14.14 months) in the individualized treatment group(P=0.041).The time to progression was 4.8 months(95%CI was 4.12 months to 5.48 months) in the standard treatment group and 4.7 months(95%CI was 3.88 months to 5.52 months) in the individualized treatment group(P=0.395).Conclusion: The median survival time has extended in the individualized treatment group.But individualized therapy in advanced NSCLC guiding by detection of ERCC1 protein has not reflected advantage in response rate,overall survival and time to progression.Additional studies are warranted to optimize detections of biomarkers in guiding rational clinical chemotherapy regimens.