ROYAL-MARSDEN PHASE-III TRIAL OF FLUOROURACIL WITH OR WITHOUT INTERFERON ALFA-2B IN ADVANCED COLORECTAL-CANCER

Purpose: Phase II studies have shown that the combination of interfero n alfa-2b (IFN) and fluorouracil (5-FU) is active in patients with met astatic colon cancer. This study was designed to investigate whether t reatment with the combination of IFN and 5-FU could improve the respon se rate, duration of response, or survival compared with treatment wit h 5-FU alone. Patients and Methods: Patients with histologically confi rmed advanced colorectal cancer were randomized to receive 5-FU 750 mg /m(2)/d by continuous infusion for 5 consecutive days followed by week ly bolus 5-FU 750 mg/m(2) either with or without IFN 10 MU subcutaneou sly three times weekly. Treatment wets continued until disease progres sion or unacceptable toxicity for up to 12 months. Results: Radiologic response was observed in 26 of 106 assessable patients (25%): 10 of 5 2 (19%) in the group that received 5-FU plus IFN (all partial response s [PRs]) and 16 of 54 (30%) in the 5-FU-alone group (three complete re sponses [CRs] and 13 PRs) (P=.21). There was similarly no significant difference between the two groups in progression-free survival (median , 3 months), 1-year survival, or overall survival (median, 8 months). However, patients who received IFN did experience significantly more t oxicity in the form of leukopenia (P=.013), lymphopenia (P=.01), depre ssion (P=0.14), and alopecia (P=.002), and were significantly more lik ely to be withdrawn due to adverse events (P=.003). There were four to xic deaths, all of which occurred in patients who had received IFN. Co nclusion: At the doses and schedules used in this study, IFN affords n o benefit to 5-FU in terms of response and survival and significantly increases toxicity for patients with advanced colorectal cancer. (C) 1 995 by American Society of Clinical Oncology.