Clinical trials of fluorouracil with alpha-interferon in advanced colorectal carcinomas

Three clinical trials have been conducted with fluorouracil (5-FU) and recombinant interferon alfa-2a (rIFN-alpha 2a) in the treatment of advanced colorectal carcinoma. The regimen consisted of 5-FU (750 mg/m2/d) as an intravenous continuous infusion for 5 consecutive days followed by a week's rest. Weekly bolus 5-FU (750 mg/m2) was subsequently administered. Nine million units of rIFN-alpha 2a was administered subcutaneously three times weekly. The initial clinical trial conducted by investigators from the Albert Einstein Cancer Center (New York, NY) reported a 76% response rate with 13 of 17 patients responding. When this clinical trial was extended to 32 patients, 20 patients (63%) achieved partial responses. Investigators from the University of Texas M.D. Anderson Cancer Center (Houston, TX) enrolled 45 evaluable patients and reported 15 partial responses and one clinical complete response (response rate, 36%). A similar trial was conducted at Memorial Sloan-Kettering Cancer Center (New York, NY) with nine of 35 patients (26%) experiencing partial responses. Grades 3 to 4 toxicities in these three trials included mucositis, diarrhea, leukopenia, and neurotoxicity. Four treatment-related deaths were reported, with three of these deaths ascribed to profuse watery diarrhea associated with leukopenia. Current randomized trials are comparing this regimen with 5-FU plus folinic acid. Future strategies will examine alternative schedules of 5-FU with interferon, and will attempt to better define the mechanism of interaction.