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.

Abstract

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/m(2)/d for 56 days every 9 weeks for three cycles or FU 425 mg/m(2) and LV 20 mg/m(2) 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.

• Authors: Elizabeth A Poplin, Jacqueline K Benedetti, Norman C Estes, Daniel G Haller, Robert J Mayer, Richard M Goldberg, Geoffrey R Weiss, Saul E Rivkin, John S Macdonald
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 23 Issue 9 Pg. 1819-25 (Mar 20 2005) ISSN: 0732-183X [Print] United States
• PMID: 15774775 (Publication Type: Clinical Trial, Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Levamisole
• Leucovorin
• Fluorouracil

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Chemotherapy, Adjuvant
• Colonic Neoplasms (drug therapy, mortality, pathology)
• Disease-Free Survival
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Humans
• Infusions, Intravenous
• Leucovorin (administration & dosage, adverse effects)
• Levamisole (administration & dosage)
• Male
• Middle Aged