title: Phase II trial of cetuximab in combination with fluorouracil, leucovorin, and oxaliplatin in the first-line treatment of metastatic colorectal cancer.
abstract: OBJECTIVE
  This phase II study investigated the efficacy and safety of cetuximab combined with standard oxaliplatin-based chemotherapy (infusional fluorouracil, leucovorin, and oxaliplatin [FOLFOX-4]) in the first-line treatment of epidermal growth factor receptor-expressing metastatic colorectal cancer (mCRC).
  
  
  METHODS
  The activity of cetuximab plus oxaliplatin was investigated in colon cancer cell lines and xenograft models. In the clinical study, patients with mCRC received on day 1 of a 14 day cycle, cetuximab (initial dose 400 mg/m(2) during week 1, then 250 mg/m(2) weekly) followed by FOLFOX-4 (oxaliplatin 85 mg/m(2) on day 1; leucovorin 200 mg/m(2) on days 1 and 2, followed by fluorouracil 400 mg/m(2) bolus then 600 mg/m(2) intravenous infusion during 22 hours on days 1 and 2).
  
  
  RESULTS
  The preclinical studies confirmed the supra-additive activity of cetuximab to oxaliplatin. In the clinical study, 43 patients were included, with a median age of 65 years (range, 43 to 78 years). Response rates (RRs) were 79% (unconfirmed) and 72% (confirmed), with 95% disease control. Median progression-free survival (mPFS) and median duration of response were 12.3 and 10.8 months, respectively. Ten patients (23%) underwent resection with curative intent of previously unresectable metastases. After a median follow-up of 30.5 months, median overall survival (mOS) was 30.0 months. Cetuximab did not increase the characteristic toxicity of FOLFOX-4 and was generally well tolerated.
  
  
  CONCLUSIONS
  Cetuximab in combination with FOLFOX-4 is a highly active first-line treatment for mCRC, showing encouraging RR, mPFS, and mOS values. The treatment resulted in a high resectability rate, which could potentially result in an improved cure rate. This combination is under phase III development.
authors.affiliation: Medical Oncology Department, Vall d'Hebron University Hospital, P. Vall d'Hebron, 119-129, 08035 Barcelona, Spain. jtabernero@vhebron.net
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
authors.forename: Eric
authors.initials: E
authors.lastname: Van Cutsem
authors.forename: Eduardo
authors.initials: E
authors.lastname: Díaz-Rubio
authors.forename: Andrés
authors.initials: A
authors.lastname: Cervantes
authors.forename: Yves
authors.initials: Y
authors.lastname: Humblet
authors.forename: Thierry
authors.initials: T
authors.lastname: André
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Van Laethem
authors.forename: Patrick
authors.initials: P
authors.lastname: Soulié
authors.forename: Esther
authors.initials: E
authors.lastname: Casado
authors.forename: Chris
authors.initials: C
authors.lastname: Verslype
authors.forename: Javier Sastre
authors.initials: JS
authors.lastname: Valera
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
authors.forename: Fortunato
authors.initials: F
authors.lastname: Ciardiello
authors.forename: Oliver
authors.initials: O
authors.lastname: Kisker
authors.forename: Aimery
authors.initials: A
authors.lastname: de Gramont
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010349:Patient Compliance; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil