title: KRAS mutational status affects oxaliplatin-based chemotherapy independently from basal mRNA ERCC-1 expression in metastatic colorectal cancer patients.
abstract: BACKGROUND
  In this study, we evaluated the possibility that KRAS mutational status might be predictive of oxaliplatin (OXA) efficacy. We also explored the role of excision repair cross complementing group-1 (ERCC-1).
  
  
  METHODS
  Ninety anti-epidermal growth factor receptor-naive advanced colorectal cancer patients were retrospectively analysed. In all patients KRAS mutational status was assessed. In 60 patients mRNA ERCC-1 expression was also investigated. Response rate (RR) and progression-free survival (PFS) after FOLFOX-6±bevacizumab were evaluated according to KRAS status and mRNA ERCC-1 expression.
  
  
  RESULTS
  Among 90 patients 47% wild-type (wt) and 53% mutated (mt) KRAS tumours were found. Response rate was 26% in the wt KRAS group, whereas it was 56% in the mt KRAS group; the difference is statistically significant in the total sample (P=0.008) and when only patients receiving FOLFOX-6±bevacizumab as first-line are considered (P=0.01). Progression-free survival was longer in mt than in wt KRAS patients over all patients (10 vs 8 months, respectively, P=0.001) and in those treated as first-line (10 vs 8 months, respectively, P=0.0069). Mt KRAS patients experienced a longer survival (24 vs 18 months; P=0.01). ERCC-1 mRNA expression was not found to correlate with FOLFOX activity in our analysis.
  
  
  CONCLUSIONS
  Our results suggest that activating mutation of KRAS oncogene may predict response to OXA. Basal expression of ERCC-1 mRNA does not explain the high efficacy of FOLFOX-6 in mt KRAS patients.
authors.affiliation: Department of Medical Oncology, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli n 8, 00168 Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Basso
authors.forename: A
authors.initials: A
authors.lastname: Strippoli
authors.forename: A
authors.initials: A
authors.lastname: Orlandi
authors.forename: M
authors.initials: M
authors.lastname: Martini
authors.forename: M A
authors.initials: MA
authors.lastname: Calegari
authors.forename: G
authors.initials: G
authors.lastname: Schinzari
authors.forename: M
authors.initials: M
authors.lastname: Di Salvatore
authors.forename: T
authors.initials: T
authors.lastname: Cenci
authors.forename: A
authors.initials: A
authors.lastname: Cassano
authors.forename: L M
authors.initials: LM
authors.lastname: Larocca
authors.forename: C
authors.initials: C
authors.lastname: Barone
mesh_terms: D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D000077150:Oxaliplatin; D012333:RNA, Messenger / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D012333:RNA, Messenger; D000077150:Oxaliplatin; C071447:ERCC1 protein, human; D004720:Endonucleases