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.

PATIENTS AND 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.

CONCLUSION:

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: Michael J O'Connell, Daniel J Sargent, Harold E Windschitl, Lois Shepherd, Michelle R Mahoney, James E Krook, Sandra Rayson, Roscoe F Morton, Kendrith M Rowland Jr, John W Kugler
• Journal: Clinical colorectal cancer (Clin Colorectal Cancer) Vol. 6 Issue 2 Pg. 133-9 (Jul 2006) ISSN: 1533-0028 [Print] United States
• PMID: 16945169 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Levamisole
• Neopterin
• Leucovorin
• Fluorouracil

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Chemotherapy, Adjuvant
• Colonic Neoplasms (blood, drug therapy, mortality, surgery)
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Humans
• Leucovorin (administration & dosage, adverse effects)
• Levamisole (administration & dosage, adverse effects)
• Male
• Middle Aged
• Neopterin (blood)