A randomized phase II trial of 5-fluorouracil, with or without human interferon-beta, for advanced colorectal cancer.

This study compared the efficacy and safety of 5-fluorouracil (5-FU) monotherapy to that of 5-FU combined with natural human interferon-beta (IFN-beta) in patients with unresectable, advanced colorectal carcinoma. Forty-nine chemotherapy-naive patients were randomized to 5-FU alone or to the combination. All patients received 750 mg m(-2) day(-1) 5-FU for 5 days by continuous intravenous (i.v.) infusion, followed after day 15 by a weekly i.v. bolus of 750 mg m(-2). IFN-beta was injected intramuscularly three times weekly at 9 M IU. Treatment continued for 52 weeks, or until disease progression or intolerable toxicity. Clinical endpoints were tumor response, time to progression, survival and toxicity. The addition of IFN-3 to 5-FU significantly improved response rate (33.3% vs 4.5% for evaluable patients; P = 0.021), time to progression (median 7.2 vs 4.2 months; P = 0.0435), and survival time (median 15.9 vs 7.2 months; P = 0.038) without significantly increasing toxicity compared to 5-FU alone. Cumulative 5-FU dose was higher with combined therapy (P < 0.001): more patients receiving monotherapy discontinued treatment because of disease progression. Fever was more frequent with combined therapy (P = 0.008); there were no other differences in toxicity. The only grade IV toxicity observed was neutropenia (two patients per group). A randomized phase III trial has been initiated to confirm the synergy between 5-FU and IFN-beta.