Adjuvant 5-Fluorouracil and Leucovorin With or Without Interferon Alfa-2a in Colon Carcinoma: National Surgical Adjuvant Breast and Bowel Project Protocol C-05

• Published in: JNCI : Journal of the National Cancer Institute 1998-12, Vol.90 (23), p.1810-1816
• Main Authors: Wolmark, Norman, Smith, Roy, Fisher, Bernard, Bryant, John, Hyams, David, Atkins, James, Dimitrov, Nikolay, Oishi, Robert, Prager, David, Fehrenbacher, Louis, Romond, Edward, Colangelo, Linda, Grem, Jean, Allegra, Carmen
• Format: Article
• Language: English
• Subjects: Antimetabolites, Antineoplastic - administration & dosage; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Chemotherapy; Chemotherapy, Adjuvant; Colon cancer; Colonic Neoplasms - drug therapy; Colonic Neoplasms - pathology; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil - administration & dosage; Humans; Interferon alpha-2; Interferon-alpha - administration & dosage; Leucovorin - administration & dosage; Male; Medical sciences; Middle Aged; Neoplasm Staging; Pharmacology. Drug treatments; Recombinant Proteins; Survival Analysis; Toxicology; Treatment Outcome
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/90.23.1810

Background: National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol C-03 showed a benefit from leucovorin (LV)-modulated 5-fluorouracil (5-FU) adjuvant therapy (5-FU + LV) in patients with Dukes' stage B or C carcinoma of the colon. Preclinical and clinical phase I/II data suggested that interferon alfa-2a (IFN) enhanced the efficacy of 5-FU therapy. Accordingly, in NSABP protocol C-05, the addition of recombinant IFN to 5-FU + LV adjuvant therapy was evaluated. Methods: Data are presented for 2176 patients with Dukes' stage B or C cancer entered onto protocol C-05 during the period from October 1991 through February 1994. Individuals with an Eastern Cooperative Oncology Group performance status of 0-2 (ranges from fully active to ambulatory and capable of self-care but unable to work), a life expectancy of at least 10 years, and curative resection were stratified by sex, disease stage, and number of involved lymph nodes and were randomly assigned to receive either 5-FU + LV or 5-FU + LV + IFN; the mean time on the study as of June 30, 1997, was 54 months. All statistical tests were two-sided. Results: There was no statistically significant difference in either disease-free survival (5-FU + LV, 69%; 5-FU + LV + IFN, 70%) or overall survival (5-FU + LV, 80%; 5-FU + LV + IFN, 81%) at 4 years of follow-up. Toxic effects of grade 3 or higher were observed in 61.8% of subjects in the group treated with 5-FU + LV and in 72.1% of subjects in the group treated with 5-FU + LV + IFN; fewer patients in the latter group completed protocol-mandated 5-FU + LV therapy than in the former group (77.1% versus 88.5%). Conclusion: The addition of IFN to 5-FU + LV adjuvant therapy confers no statistically significant benefit, but it does increase toxicity.