title: FOLFOX4 with cetuximab vs. UFOX with cetuximab as first-line therapy in metastatic colorectal cancer: The randomized phase II FUTURE study.
abstract: BACKGROUND
  The purpose of this study was to assess the efficacy and safety of FOLFOX4, comprising infusional 5-fluorouracil (5-FU)/leucovorin (LV) and oxaliplatin, with cetuximab compared with UFOX, comprising UFT, an oral prodrug of 5-FU, LV, and oxaliplatin, with cetuximab as first-line treatment for mCRC.
  
  
  METHODS
  Patients, unselected by tumor KRAS status, were randomized 1:1 to FOLFOX4 with cetuximab or UFOX with cetuximab. Treatment was continued until disease progression or unacceptable toxicity. The primary end point, assessed in the intention-to-treat population, was progression-free survival (PFS). Secondary end points included tumor response, overall survival, and safety. Outcome according to KRAS mutation status was investigated.
  
  
  RESULTS
  Recruitment was curtailed at 302 patients after reporting of the importance of tumor KRAS mutation status for cetuximab activity. Baseline characteristics were balanced between treatment groups. PFS was significantly longer in the FOLFOX4 with cetuximab group compared with UFOX with cetuximab group (median 8.2 vs. 6.6 months; hazard ratio, 0.68; 95% confidence interval [CI], 0.52-0.89; P = .0048). The response rate was also significantly greater in the FOLFOX4 with cetuximab group (51.3% vs. 37.5%, respectively; odds ratio, 1.76; 95% CI, 1.11-2.78; P = .0160), although overall survival was comparable. In the KRAS wild type subgroup, efficacy outcomes were similar to those in the intention-to-treat population. Side effect profiles were manageable and consistent with expectations.
  
  
  CONCLUSIONS
  In the first-line treatment of mCRC, UFOX with cetuximab had an acceptable safety profile but inferior activity compared with FOLFOX4 with cetuximab in relation to PFS and response. The regimens were comparable with regard to overall survival.
authors.affiliation: Institut de Cancerologie de l'Ouest - Centre René Gauducheau, Saint-Herblain, France. Electronic address: jean-yves.douillard@ico.unicancer.fr.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Douillard
authors.affiliation: Centrum Onkologii, Instytut im. M. Sklodowskiej-Curie, Krakow, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Zemelka
authors.affiliation: Department of Medical Oncology, Aristotle University of Thessaloniki School of Medicine, Papageorgiou Hospital, Thessaloniki, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
authors.affiliation: UOC di Oncologia Medica, Università Cattolica del S. Cuore, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Barone
authors.affiliation: Merck KGaA, Darmstadt, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schlichting
authors.affiliation: Cancer Communications and Consultancy Ltd, Knutsford, Cheshire, UK.
authors.forename: Jim
authors.initials: J
authors.lastname: Heighway
authors.affiliation: Merck KGaA, Darmstadt, Germany.
authors.forename: S Peter
authors.initials: SP
authors.lastname: Eggleton
authors.affiliation: Siriraj Hospital, Bangkok, Thailand.
authors.forename: Vichien
authors.initials: V
authors.lastname: Srimuninnimit
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009944:Organoplatinum Compounds; D011355:Prodrugs / Q000008:administration & dosage / Q000009:adverse effects; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011355:Prodrugs; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil
keywords: Chemotherapy; EGFR antibody; KRAS; Oxaliplatin; UFT