Background: Due to the possibility of a synergistic effect between Interferon (IFN-alpha) and 5-fluorouracil (5-FU), a phase II trial was conducted in metastatic renal cell carcinoma (MRCC) combining recombinant IFN-alpha, 5-FU and prednisone. Prednisone has been shown to decrease IFN-alpha-related toxicity without reducing the response rate.
Patients and methods: Thirty-one patients with measurable MRCC were entered into the trial; 16 of them had lung metastases only. In 26 patients (nos. 6-31) the following dose schedule was applied during an 8-week treatment cycle: IFN-alpha (Roferon, Roche, Basel, Switzerland): 12 x 10(6)U s.c. 3 times weekly; Days 1-5: 5-FU: 600 mg/m2/day continuous i.v. infusion; Weeks 3-8: 5-FU 600 mg/m2 x 1 weekly (bolus i.v.); prednisone: 10 mg x 2 per os daily for 2 weeks, and thereafter 5 mg x 2. In the first 5 patients higher doses of 5-FU led to unacceptable toxicity and subsequent dose alteration of the trial schedule. All 31 patients were evaluable for response. Seventy treatment cycles were given.
Results: One complete and 6 partial responses were observed (response rate: 23%, 95% CI: 10%-41%), with a median response duration of 11 months. Except in one patient, hematological toxicity was confined to grades I and II. Eight patients developed grade III oral mucositis. Adverse cardiac events were observed in 3 patients. Dose modifications of 5-FU were necessary in 16 cycles. The IFN-alpha doses were transiently reduced during 8 cycles.
Conclusion: The assessed combination of IFN-alpha, 5-FU and prednisone is moderately active in MRCC, with response rates similar to those seen in patients on IFN-alpha monotherapy. The latter treatment approach seems preferable, as 5-FU-related toxicity (mucositis, cardiac toxicity) is averted.