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Phase III Southwest Oncology Group 9415/Intergroup 0153 Randomized Trial of Fluorouracil, Leucovorin, and Levamisole Versus Fluorouracil Continuous Infusion and Levamisole for Adjuvant Treatment of Stage III and High-Risk Stage II Colon Cancer

From the Cancer Institute of New Jersey, New Brunswick, NJ; Southwest Oncology Group Statistical Center; Puget Sound Oncology Consortium, Seattle, WA; University of Illinois College of Medicine at Peoria, Peoria, IL; University of Pennsylvania Cancer Center, Philadelphia, PA; Dana-Farber Cancer Institute, Boston, MA; University of North Carolina at Chapel Hill, Chapel Hill, NC; The University of Texas Health Science Center, San Antonio, TX; and St Vincent's Comprehensive Cancer Center, New York, NY

Address reprint requests to Southwest Oncology Group (SWOG-9415), Operations Office, 14980 Omicron Dr, San Antonio, TX 78245-3217; e-mail: pubs{at}swog.org

PURPOSE: Modest toxicity and possibly enhanced activity makes continuous-infusion fluorouracil (FU) an attractive alternative to FU plus leucovorin (FU/LV) for the adjuvant treatment of colorectal cancer. Intergroup trial 0153 (Southwest Oncology Group trial 9415) was developed to compare the efficacy of continuous-infusion FU (CIFU) plus levamisole to FU/LV plus levamisole in the adjuvant treatment of high-risk Dukes' B2 and C1 or C2 colon cancer.

PATIENTS AND METHODS: After surgery, patients were randomly assigned to CIFU 250 mg/m²/d for 56 days every 9 weeks for three cycles or FU 425 mg/m² and LV 20 mg/m² daily for 5 days every 28 to 35 days for six cycles. All patients received levamisole 50 mg tid for 3 days every other week. The primary end point was overall survival (OS).

RESULTS: The study closed in December 1999 after an interim analysis demonstrated little likelihood of CIFU showing superiority to FU/LV within the stipulated hazard ratio. A total of 1,135 patients were registered. At least one grade 4 toxicity occurred in 39% of patients receiving FU/LV and 5% of patients receiving CIFU. However, almost twice as many patients receiving CIFU discontinued therapy early compared with those receiving FU/LV. The 5-year OS is 70% (95% CI, 66% to 74%) for FU/LV and 69% (95% CI, 64% to 73%) for CIFU. The corresponding 5-year disease-free survival (DFS) is 61% (95% CI, 56% to 65%) and 63% (95% CI, 59% to 68%), respectively. For all patients, 5-year OS is 83%, 74%, and 55%; 5-year DFS is 78%, 67%, and 47% for N0, N1, and N2-3, respectively.

CONCLUSION: CIFU had less severe toxicity but did not improve DFS or OS in comparison with bolus FU/LV.

Supported in part by the following public health service Cooperative Agreement grants awarded by the National Cancer Institute, Department of Health and Human Services: CA38926, CA32102, CA15488, CA21115, CA32291, CA25224, CA22433, CA35090, CA20319, CA58416, CA45807, CA45450, CA12644, CA35119, CA58861, CA04919, CA63845, CA45377, CA46282, CA76429, CA35192, CA63844, CA58348, CA58882, CA76447, CA67575, CA04920, CA37981, CA27057, CA14028, CA58686, CA63850, CA46441, CA12213, CA58723, CA35281, CA46368, CA35262, CA58658, CA45560, CA42777, CA35261, CA67663, CA46113, CA28862, CA35178, CA13612, CA35996, CA76462, CA58415, CA35176, CA45461, 35128, CA52654, CA35431, CA16385, CA46136, CA68183, and CA74647.

Presented in part at the 36th Annual Meeting of the American Cancer Society, New Orleans, LA, May 20-23, 2000.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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