There is no standard care for metastatic renal cell carcinoma (MRCC). High and intermediate IL-2 regimens are difficult to recommend due to their high toxicity. A combination of low-dose cytokines is assumed to be effective and safe in MRCC patients. A prospective randomized study was started in 2003.

Methods: The eligibility criteria included histopathologically confirmed MRCC, ECOG PS 0—2, no autoimmune diseases, no brain metastases, and normal organ function. All patients 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/m 2 , 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. Cycles were repeated every three weeks. A response was evaluated according to RECIST every 2 cycles.

Results: 64 patients were enrolled of whom 63 were analyzed. The patients’ median age was 55.4 years (range 16—74). 55.6% of the patients had a poor prognosis (as described by Motzer et al., 2002). Bone metastases were present in 52.4%. Sixteen patients treated with IL-2 alone showed no CR, no PRs, 2 SDs, and 14 PDs. Of the 23 patients in IL-2+IFN group, 5 PRs, 8 SDs, and 10 PDs were observed, with a response rate of 21.7%. Amongst the 24 patients in 5-FU+IL-2+IFN group, 1 CR, 3 PRs, 10 SDs, and 10 PDs were shown, with a response rate of 16.7%. One-year survival was 20.0%, 81.3% and 81.0%, respectively. Flu-like syndrome was the most common side effect in the patients receiving IFN (89.1%, grade 1, CTC). Hypotension associated with IL-2 (all groups) was seen in 56.3% (grade 1 in 50% and grade 2 in 6.3%). The other toxicities were 12.7% grade 1 neutropenia and vomiting in 4.7% (group 3).

Conclusions: Small-dose IL-2 in combination with IFN and 5-FU in MRCC is feasible, tolerable, with the efficacy comparable to other more toxic therapeutic modalities.