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Fluorouracil plus Levamisole as Effective Adjuvant Therapy after Resection of Stage III Colon Carcinoma: A Final Report

Charles G. Moertel, MD; Thomas R. Fleming, PhD; John S. Macdonald, MD; Daniel G. Haller, MD; John A. Laurie, MD; Catherine M. Tangen, MS; James S. Ungerleider, MD; William A. Emerson, MD; Douglass C. Tormey, MD, PhD; John H. Glick, MD; Michael H. Veeder, MD; and James A. Mailliard, MD
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From the Mayo Clinic, Rochester, Minnesota. The Fred Hutchinson Cancer Research Center, Seattle, Washington. Temple University School of Medicine and the University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania. Grand Forks Clinic, Grand Forks, North Dakota. Ohio State University, Columbus, Ohio. St. Louis Community Clinical Oncology Program, St. Louis, Missouri. AMC Cancer Research Center, Denver, Colorado. Oncology Hematology Associates, Peoria, Illinois. St. Joseph Hospital and Creighton University Cancer Center, Omaha, Nebraska. Requests for Reprints: Janet Graff and Thomas R. Fleming, Southwest Oncology Group (SWOG-8591), Operations Office, 14980 Omincron Drive, San Antonio, TX, 78245. Acknowledgments: The authors thank Ms. Deborah Papenfus and Mr. John VanDamme, BS, BA, for data management and statistical assistance. Grant Support: In part by U.S. Public Health Service grants CA-25224, CA-31224, and CA-37404 (to the North Central Cancer Treatment Group and Mayo Clinic); CA-21115, CA-37403, and CA-39088 (to the Eastern Cooperative Oncology Group); CA-32102, CA-38926, and CA-3909 (to the Southwest Oncology Group); and CA-38926 (to the Fred Hutchinson Cancer Research Center) and by grants to individual participating institutions from the National Cancer Institute.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1995;122(5):321-326. doi:10.7326/0003-4819-122-5-199503010-00001
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Objective: To determine the effectiveness of two adjuvant therapy regimens in improving surgical cure rates in stage III (Dukes stage C) colon cancer.

Design: Randomized, concurrently controlled clinical trial.

Setting: Major cancer centers, universities, and community clinics affiliated with the North Cancer Treatment Group, the Southwest Oncology Group, and the Eastern Cooperative Oncology Group.

Patients: Those who had had curative-intent resections of stage III colon cancer in the previous 1 to 5 weeks.

Intervention: Patients were assigned to observation only, to levamisole alone (50 mg orally three times/d for 3 days, repeated every 2 weeks for 1 year), or to this regimen of levamisole plus fluorouracil (450 mg/m2 body surface area intravenously daily for 5 days and then, beginning at 28 days, weekly for 48 weeks).

Measurements: Rates of cancer recurrence and death. Early-and late-treatment side effects.

Results: With all 929 eligible patients able to be followed for 5 years or more (median follow-up, 6.5 years), fluorouracil plus levamisole reduced the recurrence rate by 40% (P < 0.0001) and the death rate by 33% (P = 0.0007). Levamisole reduced the recurrence rate by only 2% and the death rate by only 6%. With few exceptions, toxicity was mild and patient compliance was excellent. No evidence of late side effects was seen.

Conclusion: Fluorouracil plus levamisole is tolerable adjuvant therapy to surgery; it has been confirmed to substantially increase cure rates for patients with high-risk (stage III) colon cancer. It should be considered standard treatment for all such patients not entered into clinical trials.


Grahic Jump Location
Figure 1.
Recurrence-free interval according to treatment arm.

Patients who died without recurrence have been censored. 5-FU = fluorouracil.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Patterns of recurrence sites according to treatment arm.

Patients with more than one site are included in each involved recurrence site; patients who refused their treatment assignment are not included.

Grahic Jump Location
Grahic Jump Location
Figure 3.
Survival according to treatment arm.

5-FU = fluorouracil.

Grahic Jump Location




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