A PHASE-II RANDOMIZED TRIAL OF 5-FLUOROURACIL WITH OR WITHOUT INTERFERON ALPHA-2A IN ADVANCED COLORECTAL-CANCER

With the association of 5-fluorouracil (5-FU) and alpha-interferon (IF N), objective responses as high as 26-63% have been reported in untrea ted patients with advanced colorectal cancer. However, grade 3-4 toxic ity has also been reported. We have conducted a prospective phase II r andomised study comparing 5-FU to 5-FU+IFN, to investigate whether the addition of IFN to a weekly 5-FU regimen devoid of significant toxici ty used at our institutions could improve the effectiveness of 5-FU wh ile maintaining acceptable toxicity. Patients with histologically prov en advanced colorectal carcinoma were randomised to receive 5-FU 500 m g m(-2) intravenous (i.v.) bolus on days 1-5 followed by 5-FU 500 mg m (-2) i.v. bolus weekly from day 15, with or without IFN alpha-2a intra muscularly (i.m.) 1.5 mU daily on days 6-12 and 3 mU i.m. daily therea fter. The treatment was administered on an outpatient basis. Response was evaluated every 3 months, and treatment continued until progressio n or after two consecutive judgements of stable disease. Response rate was the main end point of the study. Of 141 patients eligible, 72 wer e randomised to 5-FU alone (arm A) and 69 to 5-FU+IFN (arm B). Respons es were 9/72 (12.5%) in arm A and 6/69 (8.7%) in arm B; complete respo nses were three in arm A and two in arm B. Progression-free survival ( median 4 months) and survival (median 12 months) were identical in the two arms. Toxicity was almost absent in arm A and moderate in arm B, represented mainly by haematological toxicity (usually leucopenia). In conclusion, overall survival was good in both arms of treatment and t oxicity was moderate. While the response rate with 5-FU alone was in a ccord with the literature data, response to 5-FU + IFN was lower than expected. Al least at this dosage and schedule, the association of 5-F U and IFN is no better than 5-FU alone and is of no clinical interest.