Phase II study of fluorouracil, leucovorin, and interferon alfa-2a in metastatic colorectal carcinoma

J. L. Grem, E. Jordan, M. E. Robson, R. A. Binder, J. M. Hamilton, S. M. Steinberg, S. G. Arbuck, R. A. Beveridge, A. N. Kales, J. A. Miller, R. B. Weiss, N. McAtee, A. Chen, B. Goldspiel, E. Sover, C. J. Allegra

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Purpose: To test the activity of a regimen of interferon alfa-2a (IFN α- 2a) 5 x 106 U/m2 subcutaneously (SC) days 1 through 7 combined with leucovorin 500 mg/m2/d intravenously (IV) over 30 minutes and fluorouracil (5-FU) 370 mg/m2/d through IV push 1 hour after leucovorin days 2 through 6 in a phase II study. Patients and Methods: Forty-six patients with a good performance status (PS) with measurable colorectal cancer and no prior therapy for metastatic disease were entered. Cycles were repeated at 3-week intervals if toxicity had resolved. The 5-FU dose was increased by 15% if toxicity was mild, and decreased by 15% for grade 3 to 4 nonhematologic or grade 4 hematologic toxicity. Results: Three complete responses (CRs) and 21 partial responses (PRs) were seen among 44 assessable patients (54%; 95% confidence interval, 39% to 70%). A moderately strong association was noted between PS and response: PS 0 (n = 26), two CRs and 15 PRs (65%); PS 1 (n = 13), one CR and six PRs (54%); PS 2 (n = 5), zero CRs and zero PRs (0%; two- tailed P = .026). With a median follow-up duration of 18.8 months, the median time to treatment failure (TTF) and survival were 7.8 months and 16.3 months, respectively. Doses were escalated to 425 mg/m2/d 5-FU in 10 patients, but only four tolerated the higher dose. When expressed as the most severe degree of toxicity experienced by each patient across all cycles, grade 3 to 4 toxicity of the following types was observed; mucositis, 37%; diarrhea, 40%; rash, 7%; fatigue, 14%; granulocytopenia, 13%. Dose-limiting toxicity at 370 mg/m2/d 5-FU eventually occurred in 28 patients (61%). Twelve patients (26%) required an IFN α-2a dose reduction for constitutional toxicity. Conclusion: This regimen has promising activity in advanced colorectal cancer, particularly in patients with an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1.

Original languageEnglish (US)
Pages (from-to)1737-1745
Number of pages9
JournalJournal of Clinical Oncology
Issue number9
StatePublished - Jan 1 1993


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Grem, J. L., Jordan, E., Robson, M. E., Binder, R. A., Hamilton, J. M., Steinberg, S. M., Arbuck, S. G., Beveridge, R. A., Kales, A. N., Miller, J. A., Weiss, R. B., McAtee, N., Chen, A., Goldspiel, B., Sover, E., & Allegra, C. J. (1993). Phase II study of fluorouracil, leucovorin, and interferon alfa-2a in metastatic colorectal carcinoma. Journal of Clinical Oncology, 11(9), 1737-1745.