Fluorouracil and recombinant interferon alfa-2a in advanced gastrointestinal neoplasms

Based on preclinical studies which demonstrated synergy between recombinant interferon alfa-2a (rIFN alpha-2a) and 5-fluorouracil (5FU), clinical studies have been initiated to investigate this combination. The initial study conducted by investigators from the Albert Einstein Cancer Center reported a response rate of 76% with 13/17 patients with advanced colorectal carcinoma responding. To further evaluate this regimen, two clinical trials have been conducted in previously untreated advanced colorectal carcinoma patients with measurable disease. The regimen consisted of 5FU administered as a continuous infusion, 750 mg/m2/d for 5 consecutive days. Intravenous bolus administration of 5FU 750 mg/m2 was given weekly for 7 weeks starting 1 week after completion of the continuous infusion. rIFN alpha-2a, 9 MU, was administered subcutaneously three times weekly. In The University of Texas M.D. Anderson Cancer Center trial, 15/45 evaluable patients experienced partial response, and one patient achieved a complete response for an overall response rate of 35%. Another trial of this regimen conducted by Memorial Sloan-Kettering has reported a 26% response rate with 9/34 evaluable patients experiencing a partial response. Current randomized trials comparing this schedule of 5FU with rIFN alpha-2a to 5FU plus folinic acid or single-agent 5FU may clarify its role in the treatment of advanced colorectal carcinomas.