Combined Immunotherapy with Low-dose IL-2 Plus IFN-α for Metastatic Renal Cell Carcinoma: Survival Benefit for Selected Patients with Lung Metastasis and Serum Sodium Level

Objective: To clarify the survival benefit of immunotherapy for renal cell carcinoma patients with lung metastasis using low-dose interleukin-2 plus interferon-alpha, we examined survival outcomes and factors associated with prognosis. Methods: This was a multicenter prospective study. Nephrectomized renal cell carcinoma patients with lung metastasis were treated with interleukin-2 (0.7 x 10(6) unit, 5 days a week) and interferon-alpha (6 x 10(6) IU, 3 days a week) for the first 8 weeks, and then with both interleukin-2 and interferon-alpha, 2 or 3 days a week for 16 additional weeks. Results: Median follow-up period for 42 patients was 28.3 months (range: 4.2-43.8). Two-year overall survival rate was 82% and the probability of 3 year survival rate was 71%. Median progression-free survival was 10.4 months. While no difference was found in survival among patients assessed as complete response, partial response and no change, survival of patients assessed as NC or better was significantly better than those assessed as progressive disease (P < 0.0001). Furthermore, multivariate analyses identified pre-treatment serum sodium (P = 0.004) as an independent prognostic factor. The sodium level was also statistically associated with tumor response (p = 0.035). Patients with normal sodium level survived significantly longer (P = 0.0005) than those with low sodium level showing median survival of 12.2 months. Conclusions: Combination immunotherapy with low-dose interleukin-2 plus interferon-alpha showed survival benefit for patients with lung metastasis whose tumor responded as no change or better. This combination immunotherapy could be beneficial for patients selected by metastatic organ and their pre-treatment serum sodium level.