INTERFERON-ALPHA, 5-FU AND PREDNISONE IN METASTATIC RENAL-CELL CARCINOMA - A PHASE-II STUDY

Background: Due to the possibility of a synergistic effect between Int erferon (IFN-alpha) and 5-Fluorouracil (5-FU), a phase II trial was co nducted in metastatic renal cell carcinoma (MRCC) combining recombinan t IFN-alpha, 5-FU and prednisone. Prednisone has been shown to decreas e IFN-alpha-related toxicity without reducing the response rate. Patie nts 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 tr eatment cycle: IFN-alpha (Roferon(R), 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.); pred nisone: 10 mg x 2 per os daily for 2 weeks, and thereafter 5 mg x 2. I n the first 5 patients higher doses of 5-FU led to unacceptable toxici ty and subsequent dose alteration of the trial schedule. All 31 patien ts were evaluable for response. Seventy treatment cycles were given. R esults: One complete and 6 partial responses were observed (response r ate: 23%, 95% CI: 10%-41%), with a median response duration of 11 mont hs. Except in one patient, hematological toxicity was confined to grad es I and II. Eight patients developed grade III oral mucositis. Advers e cardiac events were observed in 3 patients. Dose modifications of 5- FU were necessary in 16 cycles. The IFN-alpha doses were transiently r educed during 8 cycles. Conclusion: The assessed combination of IFN-al pha, 5-FU and prednisone is moderately active in MRCC, with response r ates similar to those seen in patients on IFN-alpha monotherapy. The l atter treatment approach seems preferable, as 5-FU-related toxicity (m ucositis, cardiac toxicity) is averted.