5-FLUOROURACIL VERSUS 5-FLUOROURACIL PLUS ALPHA-INTERFERON AS TREATMENT OF METASTATIC COLORECTAL-CARCINOMA - A RANDOMIZED STUDY

Background: In 1989, S. Wadler reported very promising results (76% re sponse 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 synergi sm between the two agents. We therefore decided in 1989 to start a ran domized study comparing 5-FU alone with 5-FU plus IFN. Patients and me thods: 105 non-pretreated patients with measurable metastatic colorect al carcinoma entered into this study. The patients were randomly alloc ated either in arm A (n = 49) with 5-FU: 750 mg/m(2) i.v. CI d1-d5 fol lowed by 750 mg/m(2) 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 mo nths) than in arm A (10 months) (P < 0.05). For overall survival the d ifference was not significant after adjustment on center treatment and baseline Karnofsky status (P = 0.13). Toxicity was also greater in ar m 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 fre e survival but not of overall survival. 5-FU plus IFN is more toxic. A s IFN has no demonstrated efficacy in MCRC as a single agent, this stu dy suggests that IFN is acting as a 5-FU modulatory agent. The respons e rate observed (19.6%) is similar to the results obtained elsewhere w ith 5-FU plus leucovorin.