ERCC1, toxicity and quality of life in advanced NSCLC patients randomized in a large multicentre phase III trial.

AIM: Excision repair cross complementation group 1 (ERCC1) is a promising biomarker in advanced non-small cell lung cancer (NSCLC). However, current evidence regarding the impact of ERCC1 on toxicity and quality of life (QOL) is limited. PATIENTS AND METHODS: Four hundred and forty three patients with advanced NSCLC were enroled in a phase III trial and randomized to triplet chemotherapy or standard doublet regimen. Immunohistochemical evaluation for ERCC1-status was mainly performed on bioptic material. Toxicity and patient-reported QOL were correlated to ERCC1-status. RESULTS: We observed a significantly improved outcome in patients with ERCC1-negative (ERCC1-neg) tumours and demonstrated interaction between ERCC1-status and adenocarcinomas. Numerically more toxicity was observed in the entire population of ERCC1-neg tumours and reached significance in patients with adenocarcinomas regarding leukopenia (P=0.015), nausea/vomiting (P=0.040) and neurotoxicity (P=0.037). Mean change in QOL in the entire population was -13.33 (ERCC1-neg; P=0.001) and -2.25 (ERCC1-positive (ERCC1-pos): P=0.607) and -14.86 (ERCC1-neg; P=0.006) and 0 (ERCC1-pos) in patients with adenocarcinomas. CONCLUSIONS: Patient-reported QOL deteriorated significantly among survival-favourable ERCC1-neg patients possibly due to increased toxicity especially in patients with adenocarcinomas. Our novel findings emphasise strict demands for careful patient selection, proper methodology and prospective validation of ERCC1 to prove a true survival benefit before clinical implementation. [ABSTRACT FROM AUTHOR]