@article{1e081060ccfd42939ce66b9922fceba0,
title = "Randomized clinical trial of high-dose levamisole combined with 5-flourouracil 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.",
keywords = "Chemotherapy, Neurologic toxicity, Surgery, Vomiting",
author = "O'Connell, {Michael J.} and Sargent, {Daniel J.} and Windschitl, {Harold E.} and Lois Shepherd and Mahoney, {Michelle R.} and Krook, {James E.} and Sandra Rayson and Morton, {Roscoe F.} and Rowland, {Kendrith M.} and Kugler, {John W.}",
note = "Funding Information: and was supported in part by Public Health Service grants CA-25224, CA-37404, CA-63848, CA-35195, CA-52352, CA-35101, CA-35269, CA-37417, CA-35448, CA-63849, CA-35272, CA-35113, CA-60276, CA-35103, CA-35415 and CA77202 from the National Cancer Institute Department of Health and Human Services. Additional participating institutions include Michigan Cancer Consortium, Ann Arbor, MI 48106 (Philip J. Stella, MD); Siouxland Hematology-Oncology Associates, Sioux City, IA 51105 (Donald Wender, MD); Iowa Oncology Research Association CCOP, Des Moines, IA 50314 (Roscoe F. Morton, MD); Iowa Oncology Research Association CCOP, Toledo Community Hospital Oncology Program (Paul L. Schaefer, MD); Medcenter One Health Systems, Bismarck, ND 58506 (Edward J. Wos, DO); Cedar Rapids Oncology Project CCOP, Cedar Rapids, IA 52403 (Martin Wiesenfeld, MD); Meritcare Hospital CCOP, Fargo, ND 58122 (Preston Steen, MD); Geisinger Clinic & Medical Center CCOP, Danville, PA 17822 (Albert Bernath, MD); Altru Health Systems, Grand Forks, ND 58201 (Tudor Dentchev, MD); Missouri Valley Cancer Consortium, Omaha, NE 68106 (James A. Mailliard, MD); Ochsner CCOP, New Orleans, LA 70121 (Carl G. Kardinal, MD); Rapid City Regional Oncology Group, Rapid City, SD 57709 (Larry P. Ebbert, MD); Scottsdale CCOP, Scottsdale, AZ 85259 (Tom R. Fitch, MD); Sioux Community Cancer Consortium, Sioux Falls, SD 57105 (Loren K. Tschetter, MD); Toledo Community Hospital Oncology Program CCOP, Toledo, OH 43623 (Paul L. Schaefer, MD).",
year = "2006",
month = jul,
doi = "10.3816/CCC.2006.n.030",
language = "English (US)",
volume = "6",
pages = "133--139",
journal = "Clinical colorectal cancer",
issn = "1533-0028",
publisher = "Elsevier",
number = "2",
}