Randomized clinical trial of high-dose levamisole combined with 5-fluorouracil and leucovorin as surgical adjuvant therapy for high-risk colon cancer.
BACKGROUND
Levamisole combined with 5-fluorouracil (5-FU) was previously shown to significantly reduce tumor relapses and improve patient survival when given postoperatively in patients with resected stage III colon cancer. Laboratory investigations subsequently documented a direct dose-dependent enhancement of 5-FU cytotoxicity with increasing concentrations of levamisole against human cancer cell lines. A clinical trial was designed to test the value of levamisole given at its maximum tolerated dose in combination with 5-FU-based chemotherapy.


METHODS
Eight hundred seventy-eight patients who had undergone complete surgical resection of high-risk stage II/III colon cancer were stratified by known prognostic factors and randomized to receive 1 of 2 treatment regimens: standard-dose levamisole combined with 5-FU and leucovorin; or high-dose levamisole combined with the same chemotherapy. Serum neopterin was monitored in a cohort of patients to evaluate immune function.


RESULTS
Severe vomiting and neurologic side effects required reduction in the dose of levamisole that could be safely administered on the high-dose levamisole regimen. There were no significant differences in disease-free survival, overall survival, or levels of serum neopterin between the treatment regimens.


CONCLUSIONS
It was not possible to improve the efficacy of surgical adjuvant chemotherapy for patients with high-risk colon cancer by giving levamisole at its maximum tolerated dose in combination with 5-FU and leucovorin. High rates of severe gastrointestinal and neurologic side effects were observed with the high-dose levamisole regimen.
O'Connell
Michael J
MJ
Department of Medical Oncology, Allegheny General Hospital, Pittsburgh, PA, USA.
Sargent
Daniel J
DJ
Windschitl
Harold E
HE
Shepherd
Lois
L
Mahoney
Michelle R
MR
Krook
James E
JE
Rayson
Sandra
S
Morton
Roscoe F
RF
Rowland
Kendrith M
KM
Kugler
John W
JW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D007978:Levamisole / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood
D007978:Levamisole; D019798:Neopterin; D002955:Leucovorin; D005472:Fluorouracil