Randomized clinical trial of high-dose levamisole combined with 5-flourouracil and leucovorin as surgical adjuvant therapy for high-risk colon cancer

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, John W. Kugler

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)133-139
Number of pages7
JournalClinical Colorectal Cancer
Volume6
Issue number2
StatePublished - 2006

Fingerprint

Levamisole
Leucovorin
Colonic Neoplasms
Randomized Controlled Trials
Fluorouracil
Neopterin
Therapeutics
Maximum Tolerated Dose
Nervous System
Drug Therapy
Survival
Adjuvant Chemotherapy
Serum
Disease-Free Survival
Vomiting
Neoplasms
Clinical Trials
Recurrence
Cell Line

Keywords

  • Chemotherapy
  • Neurologic toxicity
  • Surgery
  • Vomiting

ASJC Scopus subject areas

  • Oncology

Cite this

O'Connell, M. J., Sargent, D. J., Windschitl, H. E., Shepherd, L., Mahoney, M. R., Krook, J. E., ... Kugler, J. W. (2006). Randomized clinical trial of high-dose levamisole combined with 5-flourouracil and leucovorin as surgical adjuvant therapy for high-risk colon cancer. Clinical Colorectal Cancer, 6(2), 133-139.

Randomized clinical trial of high-dose levamisole combined with 5-flourouracil and leucovorin as surgical adjuvant therapy for high-risk colon cancer. / O'Connell, Michael J.; Sargent, Daniel J.; Windschitl, Harold E.; Shepherd, Lois; Mahoney, Michelle R.; Krook, James E.; Rayson, Sandra; Morton, Roscoe F.; Rowland, Kendrith M.; Kugler, John W.

In: Clinical Colorectal Cancer, Vol. 6, No. 2, 2006, p. 133-139.

Research output: Contribution to journalArticle

O'Connell, MJ, Sargent, DJ, Windschitl, HE, Shepherd, L, Mahoney, MR, Krook, JE, Rayson, S, Morton, RF, Rowland, KM & Kugler, JW 2006, 'Randomized clinical trial of high-dose levamisole combined with 5-flourouracil and leucovorin as surgical adjuvant therapy for high-risk colon cancer', Clinical Colorectal Cancer, vol. 6, no. 2, pp. 133-139.
O'Connell, Michael J. ; Sargent, Daniel J. ; Windschitl, Harold E. ; Shepherd, Lois ; Mahoney, Michelle R. ; Krook, James E. ; Rayson, Sandra ; Morton, Roscoe F. ; Rowland, Kendrith M. ; Kugler, John W. / Randomized clinical trial of high-dose levamisole combined with 5-flourouracil and leucovorin as surgical adjuvant therapy for high-risk colon cancer. In: Clinical Colorectal Cancer. 2006 ; Vol. 6, No. 2. pp. 133-139.
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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.",
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AU - Windschitl, Harold E.

AU - Shepherd, Lois

AU - Mahoney, Michelle R.

AU - Krook, James E.

AU - Rayson, Sandra

AU - Morton, Roscoe F.

AU - Rowland, Kendrith M.

AU - Kugler, John W.

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