title: ERCC1, toxicity and quality of life in advanced NSCLC patients randomized in a large multicentre phase III trial.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Oncology 5073, Finsen Centre, National University Hospital, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark. adamvilmar@hotmail.com
authors.forename: Adam
authors.initials: A
authors.lastname: Vilmar
authors.forename: Eric
authors.initials: E
authors.lastname: Santoni-Rugiu
authors.forename: Jens Benn
authors.initials: JB
authors.lastname: Sørensen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004268:DNA-Binding Proteins / Q000032:analysis*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004720:Endonucleases / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011788:Quality of Life; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D003841:Deoxycytidine; C071447:ERCC1 protein, human; D004720:Endonucleases; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine