title: Randomized clinical trial of high-dose levamisole combined with 5-fluorouracil and leucovorin as surgical adjuvant therapy for high-risk colon cancer.
abstract: 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.
authors.affiliation: Department of Medical Oncology, Allegheny General Hospital, Pittsburgh, PA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Connell
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sargent
authors.forename: Harold E
authors.initials: HE
authors.lastname: Windschitl
authors.forename: Lois
authors.initials: L
authors.lastname: Shepherd
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Mahoney
authors.forename: James E
authors.initials: JE
authors.lastname: Krook
authors.forename: Sandra
authors.initials: S
authors.lastname: Rayson
authors.forename: Roscoe F
authors.initials: RF
authors.lastname: Morton
authors.forename: Kendrith M
authors.initials: KM
authors.lastname: Rowland
authors.forename: John W
authors.initials: JW
authors.lastname: Kugler
mesh_terms: 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
chemical_list: D007978:Levamisole; D019798:Neopterin; D002955:Leucovorin; D005472:Fluorouracil