PROGNOSTIC FACTORS OF THE CLINICAL-RESPONSE TO SUBCUTANEOUS IMMUNOTHERAPY WITH INTERLEUKIN-2 ALONE IN PATIENTS WITH METASTATIC RENAL-CELL CARCINOMA

The intravenous immunotherapy with interleukin 2 (IL-2) represents one of the most active therapies of metastatic renal cell carcinoma (RCC) . Recently, it has been demonstrated that IL-2 given subcutaneously in association with interferon alpha (IFN) may determine a response rate in RCC comparable to that obtained with an intravenous route of admin istration, but with a lower toxicity. Moreover, our previous data have suggested that IFN is not essential for IL-2 efficacy. On the basis o f these data, we have designed a protocol of immunotherapy with IL-2 a lone given subcutaneously in the treatment of metastatic RCC. The stud y included 48 consecutive evaluable patients. IL-2 was given at a dail y dose of 6 million IU for 5 days/week for 6 consecutive weeks, corres ponding to one IL-2 cycle. The overall response rate was 14/48 (29%; C R:1; PR:13). Response rate was significantly higher in nephrectomized than in nonnephrectomized patients, and in patients with a good compar ed to those with a low performance status. Patients with an interval b etween the diagnosis of primary renal tumor and of its metastases long er than 1 year did better than those with a lower interval, as did pat ients with a single metastasis compared to those with multiple metasta ses, while no significant difference was seen in relation to sex, age and previous IFN therapy. As far as dominant metastasis sites are conc erned, patients with liver metastases showed a response rate significa ntly lower than that seen in patients with metastases in sites other t han liver. Toxicity was low in all patients. This study shows that the subcutaneous immunotherapy with IL-2 alone is a well tolerated and ef fective therapy of metastatic RCC. The evidence of a low PS, dissemina ted tumor and liver metastases represents the most important negative prognostic factor for the response to therapy.