Adjuvant 5-fluorouracil and leucovorin with or without interferon alfa- 2a in colon carcinoma: National surgical adjuvant breast and bowel project protocol C-05

Norman Wolmark, John Bryant, Roy Smith, Jean Grem, Carmen Allegra, David Hyams, James Atkins, Nikolay Dimitrov, Robert Oishi, David Prager, Louis Fehrenbacher, Edward Romond, Linda Colangelo, Bernard Fisher

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1810-1816
Number of pages7
JournalJournal of the National Cancer Institute
Volume90
Issue number23
DOIs
StatePublished - Dec 2 1998

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Wolmark, N., Bryant, J., Smith, R., Grem, J., Allegra, C., Hyams, D., Atkins, J., Dimitrov, N., Oishi, R., Prager, D., Fehrenbacher, L., Romond, E., Colangelo, L., & Fisher, B. (1998). Adjuvant 5-fluorouracil and leucovorin with or without interferon alfa- 2a in colon carcinoma: National surgical adjuvant breast and bowel project protocol C-05. Journal of the National Cancer Institute, 90(23), 1810-1816. https://doi.org/10.1093/jnci/90.23.1810