RESUMEN
BACKGROUND: In 1989, S. Wadler reported very promising results (76% response rate) with a combination of 5-fluorouracil (5-FU) plus alpha-2a interferon (IFN) in the treatment of metastatic colorectal carcinoma (MCRC). In vitro, there are several potential explanations for synergism between the two agents. We therefore decided in 1989 to start a randomized study comparing 5-FU alone with 5-FU plus IFN. PATIENTS AND METHODS: 105 non-pretreated patients with measurable metastatic colorectal carcinoma entered into this study. The patients were randomly allocated either in arm A (n = 49) with 5-FU: 750 mg/m2 i.v. CI d1-d5 followed by 750 mg/m2 i.v. bolus once a week, or in arm B (n = 56) with 5-FU as in arm A plus IFN 9 x 10(6) IU sub-cutaneously three times a week. RESULTS: After two months of treatment we observed 1 CR and 2 PR in arm A (response rate 6.1%), 3 CR and 8 PR in arm B (response rate 19.6%), i.e., a significant difference (P = 0.05). Event-free survival was significantly higher in arm B (6 months) than in arm A (2 months) (P < 0.01), while median survival was slightly higher in arm B (12 months) than in arm A (10 months) (P < 0.05). For overall survival the difference was not significant after adjustment on center treatment and baseline Karnofsky status (P = 0.13). Toxicity was also greater in arm B. Sixteen percent of patients in arm A and 36% in arm B experienced certain grade 3-4 side effects (P < 0.05). CONCLUSION: 5-FU plus IFN is more effective than 5-FU alone in terms of response rate, event free survival but not of overall survival. 5-FU plus IFN is more toxic. As IFN has no demonstrated efficacy in MCRC as a single agent, this study suggests that IFN is acting as a 5-FU modulatory agent. The response rate observed (19.6%) is similar to the results obtained elsewhere with 5-FU plus leucovorin.