Long-term follow-up of patients with metastatic renal cell carcinoma treated with intravenous recombinant interleukin-2 in Europe

PURPOSE The median survival for patients with metastatic renal cell carcinoma (mRCC ) is generally < 1 year. Immunotherapy with high-dose recombinant interleuk in (IL)-2 has been reported to produce objective responses in approximately 15% of treated patients and is associated with durable complete responses and prolonged survival in responding patients. The impact of IL-2 therapy o n survival of metastatic renal cell carcinoma patients has begun to emerge, based on long-term follow-up data from large databases, Combinations of IL -2 and interferon alfa (IFN-alpha) have also been intensively investigated in mRCC. PATIENTS AND METHODS Between 1987 and 1990, 281 mRCC patients were treated with continuous infus ion IL-2 in three European multinational, single-arm phase II trials. Long- term treatment outcomes for these patients were analyzed, and the results a re presented here. The results of a large, randomized French cooperative gr oup trial (the Cancer Renal Cytokine [CRECY] study) that enrolled 425 patie nts between 1991 and 1995 are also summarized. Patients on this trial were randomized to treatment with IL-2 alone, IFN-alpha alone, or the combinatio n. RESULTS Among patients included in the 281-patient database, the objective response rate was 15%. Median survival was 10 months; 41% of patients were alive at 1 year, 22% were alive at 2 years, and 8% were alive at 5 years. Among pat ients with a complete or partial response, 60% and 18% were alive at 5 year s, respectively. No clinical factors were predictive for response or surviv al; however, no patient with a high endogenous IL-6 level at diagnosis resp onded to IL-2 therapy. The CRECY trial demonstrated that the combination of IL-2 and IFN-alpha induced a significantly higher response rate (P < 0.01) and significantly improved I-year event-fi ee survival (P = 0.01) compared with either agent alone, but overall survival was not significantly differ ent between the three treatment groups. CONCLUSION The European experience suggests that the 5-year survival rate for metastat ic renal cell carcinoma patients treated with high-dose continuous infusion IL-2 therapy is approximately 8% and that the majority of the therapeutic benefit is restricted to patients achieving a complete response. Therefore, given the toxicity, candidates for IL-2 therapy should be carefully select ed. The combination of IL-2 and IFN-alpha does not appear to provide additi onal survival benefit. Efforts to further improve therapeutic outcome for p atients with metastatic renal cell carcinoma should focus on understanding the underlying mechanisms of cytokine-induced tumor regression.