PHASE-III RANDOMIZED STUDY OF 2 FLUOROURACIL COMBINATIONS WITH EITHERINTERFERON-ALFA-2A OR LEUCOVORIN FOR ADVANCED COLORECTAL-CANCER

Purpose: To compare the efficacy and toxicity profiles of a combinatio n of fluorouracil (5-FU) with recombinant human interferon alfa-2a (Ro feron-A; Hoffman La-Roche AG, Basel, Switzerland) versus the combinati on of 5-FU with leucovorin (LV) in the treatment of advanced colorecta l cancer. Patients and Methods: A total of 496 previously untreated co lorectal cancer patients were randomized to receive either Roferon-A ( 9 MIU) subcutaneously three times per week, with 5-FU (750 mg/m(2)/d) by continuous intravenous (IV) infusion (CIV) on days 1 to 5, then, af ter a 9-day hiatus, as a weekly IV bolus at the same dose (IFN/5-FU); or LV (200 mg/m(2)/d) by IV infusion plus 5-FU (370 mg/m(2)/d) by IV b olus on days 1 to 5, repeated every 4 weeks (LV/5-FU). Results: There were no significant differences between IFN/5-FU and LV/5-FU in the ov erall response rate (21% v 18%), duration of response (7.3 v 6.2 month s), or survival time (median, 11.0 v 11.3 months). Toxicity profiles d iffered; constitutional symptoms and myelosuppression were more freque nt and more severe with IFN/5-FU, and gastrointestinal symptoms with L V/5-FU. More patients interrupted treatment for adverse events (AEs) w ith IFN/5-FU than with LV/5-FU. Five treatment-related deaths occurred with each regimen. Conclusion: The combination IFN/5-FU produced resp onse rates, response durations, and survival times similar to those wi th LV/5-FU. Biochemical modulation of 5-FU by either IFN or LV appears to result in equivalent efficacy; however, fewer patients were able t o tolerate the specified IFN/5-FU combination used in this study. J Cl in Oncol 13:921-928. (C) 1995 by American Society of Clinical Oncology .