title: Phase III trial of 5-fluorouracil and leucovorin plus either 3H1 anti-idiotype monoclonal antibody or placebo in patients with advanced colorectal cancer.
abstract: BACKGROUND
  The monoclonal antibody 3H1 mimics the external structure of the carcinoembryonic antigen (CEA). It therefore has the potential, via the anti-idiotypic network, to stimulate immune responses to CEA that may benefit colorectal cancer patients.
  
  
  METHODS
  A total of 630 patients with previously untreated metastatic colorectal cancer were randomised in a 2:1 fashion to receive bolus 5-fluorouracil (5-FU) and leucovorin (LV) plus either 3H1 (n = 422) or placebo (n = 208).
  
  
  RESULTS
  The addition of 3H1 to 5-FU and LV did not result in increased toxicity. Survival for the full intent-to-treat population was 14.7 months for the 3H1 arm and 15.2 months for the placebo arm (P = 0.80). Anti-CEA antibody responses were observed in 70% of patients treated with 3H1. Patients with a negative CEA response had a median survival of 8.3 months (95% CI 7.5-11.0) compared with patients with a strong response: median survival not reached (P <0.001).
  
  
  CONCLUSIONS
  3H1 is safe and effectively induces immune responses to CEA. Addition of 3H1 to 5-FU and LV was not shown to improve overall patient outcomes. However, improved survival in patients developing anti-CEA responses to 3H1 are provocative and should be studied in further clinical trials.
authors.affiliation: Royal Marsden Hospital, Sutton, Surrey, UK.
authors.forename: G
authors.initials: G
authors.lastname: Chong
authors.forename: A
authors.initials: A
authors.lastname: Bhatnagar
authors.forename: D
authors.initials: D
authors.lastname: Cunningham
authors.forename: T M
authors.initials: TM
authors.lastname: Cosgriff
authors.forename: P G
authors.initials: PG
authors.lastname: Harper
authors.forename: W
authors.initials: W
authors.lastname: Steward
authors.forename: J
authors.initials: J
authors.lastname: Bridgewater
authors.forename: M
authors.initials: M
authors.lastname: Moore
authors.forename: J
authors.initials: J
authors.lastname: Cassidy
authors.forename: R
authors.initials: R
authors.lastname: Coleman
authors.forename: F
authors.initials: F
authors.lastname: Coxon
authors.forename: C H
authors.initials: CH
authors.lastname: Redfern
authors.forename: J J
authors.initials: JJ
authors.lastname: Jones
authors.forename: R
authors.initials: R
authors.lastname: Hawkins
authors.forename: D
authors.initials: D
authors.lastname: Northfelt
authors.forename: S
authors.initials: S
authors.lastname: Sreedharan
authors.forename: F
authors.initials: F
authors.lastname: Valone
authors.forename: J
authors.initials: J
authors.lastname: Carmichael
mesh_terms: D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000628:therapy*; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008875:Middle Aged; D010919:Placebos
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D010919:Placebos; D002955:Leucovorin; D005472:Fluorouracil