title: Edrecolomab alone or in combination with fluorouracil and folinic acid in the adjuvant treatment of stage III colon cancer: a randomised study.
abstract: BACKGROUND
  Edrecolomab is a murine monoclonal antibody to the cell-surface glycoprotein 17-1A, which is expressed on epithelial tissues and on various carcinomas. Preliminary data suggested that it might be of use in the adjuvant treatment of patients with resected stage III colon cancer. We did a randomised trial in 27 countries to determine the effect of adding edrecolomab to the combination of fluorouracil and folinic acid in these patients.
  
  
  METHODS
  After surgery, 2761 patients were randomly assigned edrecolomab plus fluorouracil-folinic acid (combination therapy [n=912]); fluorouracil-folinic acid alone (chemotherapy [n=927]); or edrecolomab alone (edrecolomab monotherapy [n=922]). Patients were assessed for survival and disease recurrence after surgery. The primary endpoint tested the hypothesis that combination therapy improved overall survival relative to chemotherapy. The key secondary endpoint was to test whether edrecolomab monotherapy was non-inferior to chemotherapy in terms of disease-free survival. Analysis was by intention to treat.
  
  
  RESULTS
  Median follow-up time was 26 months (IQR 20-36). 3-year overall survival on combination therapy was no different from that on chemotherapy (74.7% vs 76.1%, hazard ratio 0.94 [95% CI 0.76-1.15], p=0.53). Disease-free survival was significantly lower on edrecolomab monotherapy than on chemotherapy (53.0% vs 65.5%, 0.62 [0.53-0.73], p<0.0001). Hypersensitivity reactions occurred in 452 (25%) patients receiving edrecolomab, causing treatment discontinuation in 71 (4%). The addition of edrecolomab to chemotherapy did not increase neutropenia, diarrhoea, or mucositis.
  
  
  CONCLUSIONS
  The addition of edrecolomab to fluorouracil and folinic acid in the adjuvant treatment of resected stage III colon cancer does not improve overall or disease-free survival, and edrecolomab monotherapy is associated with significantly shorter overall and disease-free survival than fluorouracil and folinic acid and is therefore an inferior treatment option. Edrecolomab is well tolerated and its addition to fluorouracil and folinic acid does not increase the toxicity of chemotherapy.
authors.affiliation: Department of Medical Oncology, University Medical Center St Radboud, PO Box 9101, 6500 HB Nijmegen, Netherlands. c.punt@onco.azn.nl
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
authors.forename: Attila
authors.initials: A
authors.lastname: Nagy
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Douillard
authors.forename: Arie
authors.initials: A
authors.lastname: Figer
authors.forename: Torben
authors.initials: T
authors.lastname: Skovsgaard
authors.forename: John
authors.initials: J
authors.lastname: Monson
authors.forename: Carlo
authors.initials: C
authors.lastname: Barone
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
authors.forename: Hanno
authors.initials: H
authors.lastname: Riess
authors.forename: Eugene
authors.initials: E
authors.lastname: Moylan
authors.forename: Delyth
authors.initials: D
authors.lastname: Jones
authors.forename: Juergen
authors.initials: J
authors.lastname: Dethling
authors.forename: Jessica
authors.initials: J
authors.lastname: Colman
authors.forename: Lorna
authors.initials: L
authors.lastname: Coward
authors.forename: Stuart
authors.initials: S
authors.lastname: MacGregor
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D001315:Australia; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality*; D009367:Neoplasm Staging; D012426:Russia; D016019:Survival Analysis; D016896:Treatment Outcome; D014481:United States
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000964:Antimetabolites, Antineoplastic; C400149:Edrecolomab; D002955:Leucovorin; D005472:Fluorouracil