PHASE-III RANDOMIZED STUDY TO COMPARE INTERFERON ALFA-2A IN COMBINATION WITH FLUOROURACIL VERSUS FLUOROURACIL ALONE IN PATIENTS WITH ADVANCED COLORECTAL-CANCER

Purpose: To compare the efficacy and toxicity profiles of a combinatio n of fluorouracil (5-FU) and recombinant human interferon alfa-2a ([IF N alpha 2a] Roferon-A; Hoffmann-LaRoche, Basel, Switzerland) versus 5- FU alone in the treatment of advanced colorectal cancer (ACC). Patient s and Methods: A total of 245 previously untreated ACC patients were r andomized to receive either IFN alpha 2a (9 million IU) subcutaneously (SC) three times weekly with 5-FU (750 mg/m(2)/d) by continuous intra venous (CIV) infusion on days 1 to 5 and then, after a 1-week hiatus, as a weekly IV bolus at the same dose (IFN/5-FU), or 5-FU alone at the same dose schedule (5-FU). Results: There were no significant differe nces between IFN/5-FU and 5-FU alone in the overall response rate (24% v 17%, P = .2), duration of response (median, 6.4 v 8.1 months), time to response (plateau at 3 months), time to progressive disease ([PD] median, 4.8 v 4.9 months), or survival duration (median, 13.9 v 13.2 m onths). Toxicity profiles were not statistically different except for constitutional symptoms, which were more frequent and more severe with IFN/5-FU. More patients interrupted treatment for adverse events (AEs ) with IFN/5-FU (34%) than with 5-FU alone (21%) (P = .03). The number of deaths (mostly unrelated to drug treatment) during the study (8%) was similar with both regimens. Conclusion: The combination IFN/5-FU p roduced a response rate, response duration, and survival duration simi lar to that of 5-FU alone. The addition of IFN to 5-FU in the doses an d schedules used in this study did not provide any further benefit ove r 5-FU alone and cannot be recommended for patients with metastatic AC C. This study confirms the value of large prospective randomized clini cal trials to determine the clinical value of regimens that emerge fro m smaller single-center phase II studies. (C) 1996 by American Society of Clinical Oncology.