Phase III trial of 5-fluorouracil and leucovorin plus either 3H1 anti-idiotype monoclonal antibody or placebo in patients with advanced colorectal cancer.
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.
Chong
G
G
Royal Marsden Hospital, Sutton, Surrey, UK.
Bhatnagar
A
A
Cunningham
D
D
Cosgriff
T M
TM
Harper
P G
PG
Steward
W
W
Bridgewater
J
J
Moore
M
M
Cassidy
J
J
Coleman
R
R
Coxon
F
F
Redfern
C H
CH
Jones
J J
JJ
Hawkins
R
R
Northfelt
D
D
Sreedharan
S
S
Valone
F
F
Carmichael
J
J
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
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D010919:Placebos; D002955:Leucovorin; D005472:Fluorouracil