title: Effect of KRAS codon13 mutations in patients with advanced colorectal cancer (advanced CRC) under oxaliplatin containing chemotherapy. Results from a translational study of the AIO colorectal study group.
abstract: BACKGROUND
  To evaluate the value of KRAS codon 13 mutations in patients with advanced colorectal cancer (advanced CRC) treated with oxaliplatin and fluoropyrimidines.
  
  
  METHODS
  Tumor specimens from 201 patients with advanced CRC from a randomized, phase III trial comparing oxaliplatin/5-FU vs. oxaliplatin/capecitabine were retrospectively analyzed for KRAS mutations. Mutation data were correlated to response data (Overall response rate, ORR), progression-free survival (PFS) and overall survival (OS).
  
  
  RESULTS
  201 patients were analysed for KRAS mutation (61.2% males; mean age 64.2 ± 8.6 years). KRAS mutations were identified in 36.3% of tumors (28.8% in codon 12, 7.4% in codon 13). The ORR in codon 13 patients compared to codon 12 and wild type patients was significantly lower (p = 0.008). There was a tendency for a better overall survival in KRAS wild type patients compared to mutants (p = 0.085). PFS in all patients was not different in the three KRAS genetic groups (p = 0.72). However, we found a marked difference in PFS between patients with codon 12 and 13 mutant tumors treated with infusional 5-FU versus capecitabine based regimens.
  
  
  CONCLUSIONS
  Our data suggest that the type of KRAS mutation may be of clinical relevance under oxaliplatin combination chemotherapies without the addition of monoclonal antibodies in particular when overall response rates are important.
  
  
  BACKGROUND
  2002-04-017.
authors.affiliation: Department of Internal Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany. Anke.Reinacher@rub.de
authors.forename: Anke
authors.initials: A
authors.lastname: Reinacher-Schick
authors.forename: Karsten
authors.initials: K
authors.lastname: Schulmann
authors.forename: Dominik P
authors.initials: DP
authors.lastname: Modest
authors.forename: Nina
authors.initials: N
authors.lastname: Bruns
authors.forename: Ulrich
authors.initials: U
authors.lastname: Graeven
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Jaworska
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.forename: Rainer
authors.initials: R
authors.lastname: Porschen
authors.forename: Dirk
authors.initials: D
authors.lastname: Arnold
authors.forename: Wolff
authors.initials: W
authors.lastname: Schmiegel
authors.forename: Andrea
authors.initials: A
authors.lastname: Tannapfel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003062:Codon; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D003062:Codon; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D000077150:Oxaliplatin; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins