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.

PATIENTS AND 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).

CONCLUSION:

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: G Chong, A Bhatnagar, D Cunningham, T M Cosgriff, P G Harper, W Steward, J Bridgewater, M Moore, J Cassidy, R Coleman, F Coxon, C H Redfern, J J Jones, R Hawkins, D Northfelt, S Sreedharan, F Valone, J Carmichael
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 17 Issue 3 Pg. 437-42 (Mar 2006) ISSN: 0923-7534 [Print] England
• PMID: 16311275 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)

Chemical References

• Antibodies, Anti-Idiotypic
• Antibodies, Monoclonal
• Placebos
• Leucovorin
• Fluorouracil

Topics

• Adult
• Aged
• Antibodies, Anti-Idiotypic (administration & dosage, adverse effects, therapeutic use)
• Antibodies, Monoclonal (administration & dosage, adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Colorectal Neoplasms (therapy)
• Fluorouracil (administration & dosage)
• Humans
• Leucovorin (administration & dosage)
• Middle Aged
• Placebos