Continuous infusion of high-dose 5-fluorouracil in combination with leucovorin and recombinant interferon-alpha-2b in patients with advanced colorectal cancer. A Multicenter Phase II study.

Background: 5-Fluorouracil (5-FU), when combined with leucovorin (LV) or interferon-alpha (IFN-α), may result in improved response rates compared with 5-FU alone in patients with advanced colorectal cancer. The authors investigated the clinical efficacy of combining these three agents for patients in this group. Methods: Forty-five patients were administered outpatient high-dose 5-FU, 60 mg/kg/48 hours (2400 mg/m2/48 hours) continuous intravenous infusion on days 1 and 2; LV, 90 mg orally every 6 hour, 8 times during 5FU infusion; and recombinant IFN-α-2b, 10 × 106 IU/dose subcutaneously on days 1, 3, and 5. Cycles were repeated weekly for 4 weeks and every 2 weeks thereafter. Results: Forty-four patients were evaluable for response, and 11 patients (25%; 95% confidence interval, 12–38%) achieved a partial response with a median duration of 11 months. Median survival time for all patients was 11 months. Grade 3 and Grade 4 toxicities occurred in 21 patients (47%), which necessitated discontinuation of treatment in 2 patients (4%); permanent dose reductions were necessary in 11 patients (24%). The addition of IFN-α produced more 5-FU-related toxicity compared with a previous study in which the same dosage and schedule of 5-FU plus LV was used. Conclusions: The efficacy of 5-FU continuous infusion combined with LV and IFN-α does not appear to differ significantly from earlier reports on treatment using 5-FU plus LV or 5-FU plus IFN-α for patients with colorectal cancer. However, this schedule of 5-FU combined with LV and IFN-α produces less toxicity compared with previous trials using bolus 5-FU plus IFN-α.