title: Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer.
abstract: OBJECTIVE
  This randomized study assessed whether the best overall response rate (ORR) of cetuximab combined with oxaliplatin, leucovorin, and fluorouracil (FOLFOX-4) was superior to that of FOLFOX-4 alone as first-line treatment for metastatic colorectal cancer. The influence of KRAS mutation status was investigated.
  
  
  METHODS
  Patients received cetuximab (400 mg/m(2) initial dose followed by 250 mg/m(2)/wk thereafter) plus FOLFOX-4 (oxaliplatin 85 mg/m(2) on day 1, plus leucovorin 200 mg/m(2) and fluorouracil as a 400 mg/m(2) bolus followed by a 600 mg/m(2) infusion during 22 hours on days 1 and 2; n = 169) or FOLFOX-4 alone (n = 168). Treatment was continued until disease progression or unacceptable toxicity. KRAS mutation status was assessed in the subset of patients with assessable tumor samples (n = 233).
  
  
  RESULTS
  The confirmed ORR for cetuximab plus FOLFOX-4 was higher than with FOLFOX-4 alone (46% v 36%). A statistically significant increase in the odds for a response with the addition of cetuximab to FOLFOX-4 could not be established (odds ratio = 1.52; P = .064). In patients with KRAS wild-type tumors, the addition of cetuximab to FOLFOX-4 was associated with a clinically significant increased chance of response (ORR = 61% v 37%; odds ratio = 2.54; P = .011) and a lower risk of disease progression (hazard ratio = 0.57; P = .0163) compared with FOLFOX-4 alone. Cetuximab plus FOLFOX-4 was generally well tolerated.
  
  
  CONCLUSIONS
  KRAS mutational status was shown to be a highly predictive selection criterion in relation to the treatment decision regarding the addition of cetuximab to FOLFOX-4 for previously untreated patients with metastatic colorectal cancer.
authors.affiliation: University Hospital, Hamburg-Eppendorf, Hamburg-Eppendorf, Germany. c.bokemeyer@uke.uni-hamburg.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Igor
authors.initials: I
authors.lastname: Bondarenko
authors.forename: Anatoly
authors.initials: A
authors.lastname: Makhson
authors.forename: Joerg T
authors.initials: JT
authors.lastname: Hartmann
authors.forename: Jorge
authors.initials: J
authors.lastname: Aparicio
authors.forename: Filippo
authors.initials: F
authors.lastname: de Braud
authors.forename: Serban
authors.initials: S
authors.lastname: Donea
authors.forename: Heinz
authors.initials: H
authors.lastname: Ludwig
authors.forename: Gunter
authors.initials: G
authors.lastname: Schuch
authors.forename: Christopher
authors.initials: C
authors.lastname: Stroh
authors.forename: Anja H
authors.initials: AH
authors.lastname: Loos
authors.forename: Angela
authors.initials: A
authors.lastname: Zubel
authors.forename: Piotr
authors.initials: P
authors.lastname: Koralewski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D010349:Patient Compliance; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil