SMALL-DOSE CYTOKINES IN COMBINATION WITH 5-FLUOROURACIL IN OLISSEMINATED RENAL CELL CARCINOMA: FINAL RESULTS OF A RANDOMIZED TRIAL

Background: High and intermediate IL-2 regimens are difficult to recommend because of great toxicity and efficacy is not sufficient. We suggest that a combination of very low-dose cytokines is effective and safe in metastatic renal cell carcinoma (MRCC) patients (pts). A prospective randomized study was started in 2003. The primary end-point was a response rate. Methods: The eligibility criteria included histopathologically confirmed MRCC, ECOG PS 0-2, no autoimmune diseases, no brain metastases, and normal organ function. All pts were randomized in three arms: IL-2 alone, 1.5 MIU, iv, t.i.w., weeks 1—3 or IL-2 1.0 MIU, iv, t.i.w., weeks 1—3 plus IFN 5 MIU, sc, t.i.w, weeks 1—3 or biochemotherapy group 5-FU, 500 mg/m2, iv, once a week, weeks 1—3 plus IL-2 1.0 MIU, iv, t.i.w., weeks 1—3 plus IFN 5 MIU, sc, t.i.w., weeks 1—3. Courses were repeated every three weeks. A response was assessed according to the RECIST every 2 courses.

Results: 64 pts were enrolled, of whom 63 were analyzed. Their median age was 55.4 years (range 16—74). 42.9% of the patients had pre- viously received chemo- or immunotherapy. 55.6 percent of the pts had poor prognosis (according to Motzer et al., 2002). Bone metastases were present in 52.4% of the pts. Sixteen patients treated with IL-2 alone showed no CR, PR, 2 SD, or 14 PD. Of 23 patients in the IL-2+IFN group, there were 5 PR, 8 SD, and 10 PD, with a response rate of 21.7%. Amongst 24 patients in the 5-FU+IL-2+IFN group, there were 1 CR, 3 PR, 10 SD, and 10 PD, with a response rate of 16.7%. One-year survival was 20.0%, 81.3% and 81.0%, respectively. The influenza-like syndrome was the most common side effect in the pts who received IFN (89.1%, grade 1, CTC). Hypotension associated with IL-2 (all groups) was seen in 56.3% (50%, grade 1 and 6.3%, grade 2). The other adverse reactions were 12.7% grade 1 neutropenia and vomiting in 4.7% pts (Group 3).

Conclusion: All regimens are well tolerated. Small-dose IL-2 alone is ineffective. 5-FU does not improve the efficacy of a cytokine combination. Small-dose IL-2 and IFN demonstrate a reasonable efficacy and can be recommend for MRCC pts outside clinical trials.

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