PURPOSE Phase II studies have shown that the combination of interferon alfa-2b (IFN) and fluorouracil (5-FU) is active in patients with metastatic colon cancer. This study was designed to investigate whether treatment with the combination of IFN and 5-FU could improve the response rate, duration of response, or survival compared with treatment with 5-FU alone. PATIENTS AND METHODS Patients with histologically confirmed advanced colorectal cancer were randomized to receive 5-FU 750 mg/m2/d by continuous infusion for 5 consecutive days followed by weekly bolus 5-FU 750 mg/m2 either with or without IFN 10 MU subcutaneously three times weekly. Treatment was continued until disease progression or unacceptable toxicity for up to 12 months. RESULTS Radiologic response was observed in 26 of 106 assessable patients (25%): 10 of 52 (19%) in the group that received 5-FU plus IFN (all partial responses [PRs]) and 16 of 54 (30%) in the 5-FU-alone group (three complete responses [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 toxicity in the form of leukopenia (P = .013), lymphopenia (P = .01), depression (P = .014), and alopecia (P = .002), and were significantly more likely to be withdrawn due to adverse events (P = .003). There were four toxic deaths, all of which occurred in patients who had received IFN. CONCLUSION At the doses and schedules used in this study, IFN affords no benefit to 5-FU in terms of response and survival and significantly increases toxicity for patients with advanced colorectal cancer.

Hill, M., Norman, A., Cunningham, D., Findlay, M., Nicolson, V., Hill, A., Iveson, A., Evans, C., Joffe, J., & Nicolson, M. (1995). Royal Marsden phase III trial of fluorouracil with or without interferon alfa-2b in advanced colorectal cancer. Journal of Clinical Oncology, 13(6), 1297–1302.