title: Cetuximab for the treatment of colorectal cancer.
abstract: BACKGROUND
  Cetuximab, an IgG1 chimeric monoclonal antibody against epidermal growth factor receptor (EGFR), has activity against colorectal cancers that express EGFR.
  
  
  METHODS
  From December 2003 to August 2005, 572 patients who had colorectal cancer expressing immunohistochemically detectable EGFR and who had been previously treated with a fluoropyrimidine, irinotecan, and oxaliplatin or had contraindications to treatment with these drugs underwent randomization to an initial dose of 400 mg of cetuximab per square meter of body-surface area followed by a weekly infusion of 250 mg per square meter plus best supportive care (287 patients) or best supportive care alone (285 patients). The primary end point was overall survival.
  
  
  RESULTS
  In comparison with best supportive care alone, cetuximab treatment was associated with a significant improvement in overall survival (hazard ratio for death, 0.77; 95% confidence interval [CI], 0.64 to 0.92; P=0.005) and in progression-free survival (hazard ratio for disease progression or death, 0.68; 95% CI, 0.57 to 0.80; P<0.001). These benefits were robust after adjustment in a multivariable Cox proportional-hazards model. The median overall survival was 6.1 months in the cetuximab group and 4.6 months in the group assigned to supportive care alone. Partial responses occurred in 23 patients (8.0%) in the cetuximab group but in none in the group assigned to supportive care alone (P<0.001); the disease was stable in an additional 31.4% of patients assigned to cetuximab and in 10.9% of patients assigned to supportive care alone (P<0.001). Quality of life was better preserved in the cetuximab group, with less deterioration in physical function and global health status scores (both P<0.05). Cetuximab treatment was associated with a characteristic rash; a rash of grade 2 or higher was strongly associated with improved survival (hazard ratio for death, 0.33; 95% CI, 0.22 to 0.50; P<0.001). The incidence of any adverse event of grade 3 or higher was 78.5% in the cetuximab group and 59.1% in the group assigned to supportive care alone (P<0.001).
  
  
  CONCLUSIONS
  Cetuximab improves overall survival and progression-free survival and preserves quality-of-life measures in patients with colorectal cancer in whom other treatments have failed. (ClinicalTrials.gov number, NCT00079066 [ClinicalTrials.gov].).
authors.affiliation: Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada. djonker@ottawahospital.on.ca
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Jonker
authors.forename: Chris J
authors.initials: CJ
authors.lastname: O'Callaghan
authors.forename: Christos S
authors.initials: CS
authors.lastname: Karapetis
authors.forename: John R
authors.initials: JR
authors.lastname: Zalcberg
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Tu
authors.forename: Heather-Jane
authors.initials: HJ
authors.lastname: Au
authors.forename: Scott R
authors.initials: SR
authors.lastname: Berry
authors.forename: Marianne
authors.initials: M
authors.lastname: Krahn
authors.forename: Timothy
authors.initials: T
authors.lastname: Price
authors.forename: R John
authors.initials: RJ
authors.lastname: Simes
authors.forename: Niall C
authors.initials: NC
authors.lastname: Tebbutt
authors.forename: Guy
authors.initials: G
authors.lastname: van Hazel
authors.forename: Rafal
authors.initials: R
authors.lastname: Wierzbicki
authors.forename: Christiane
authors.initials: C
authors.lastname: Langer
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Moore
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D066246:ErbB Receptors / Q000276:immunology*; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000068818:Cetuximab