OBJECTIVE: To evaluate the efficacy and toxicity of subcutaneous immunotherapy using a combination of recombinant interleukin-2 (r-IL2) and interferon-alpha (IFN-alpha) for the treatment of patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Initially a maximum of 45 patients with advanced RCC were to be included in the study, according to a Fleming three-stage procedure. To be included patients had to have measurable metastasis. Of a potential 45 patients with advanced RCC, 15 patients were included in the study (10 men and five women, mean age 51 years, range 25-69). From the first week of treatment r-IL2 was given subcutaneously on day 1 to 5, at 18 x 10(6) units once a day and then 9 x 10(6) units once a day for the following 5 weeks. IFN-alpha was given three times a week for the last 5 weeks. Minimum follow-up was 6 months. RESULTS: All patients initially underwent radical nephrectomy. Seven patients were found to have metastases at the time of diagnosis. All patients received ambulatory therapy, except for the first 5 days of treatment. Overall, 80% of the patients received more than 75% of the complete dose of r-IL2. One patient suffered toxicity greater than the World Health Organization (WHO) grade 2 (neutropenia). No patient had a complete or partial response, two patients had a minor response, two patients had stable disease and 11 patients had disease progression. CONCLUSIONS: Subcutaneous r-IL2 and IFN-alpha had no beneficial effect on the first 15 patients and the study was discontinued, in accordance with the Fleming rules. The dose, administration and combination of r-IL2 and IFN-alpha may explain the lack of efficacy. Other studies have shown that low doses of r-IL2 are not effective and the superiority of the combination of r-IL2 and IFN-alpha has not been proven. Therefore, a high dose of r-IL2, in association with other cytokines, chemotherapy and adoptive immunotherapy, may be the only way to improve the response rate of metastatic RCC.
OBJECTIVE: To evaluate the efficacy and toxicity of subcutaneous immunotherapy using a combination of recombinant interleukin-2 (r-IL2) and interferon-alpha (IFN-alpha) for the treatment of patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Initially a maximum of 45 patients with advanced RCC were to be included in the study, according to a Fleming three-stage procedure. To be included patients had to have measurable metastasis. Of a potential 45 patients with advanced RCC, 15 patients were included in the study (10 men and five women, mean age 51 years, range 25-69). From the first week of treatment r-IL2 was given subcutaneously on day 1 to 5, at 18 x 10(6) units once a day and then 9 x 10(6) units once a day for the following 5 weeks. IFN-alpha was given three times a week for the last 5 weeks. Minimum follow-up was 6 months. RESULTS: All patients initially underwent radical nephrectomy. Seven patients were found to have metastases at the time of diagnosis. All patients received ambulatory therapy, except for the first 5 days of treatment. Overall, 80% of the patients received more than 75% of the complete dose of r-IL2. One patient suffered toxicity greater than the World Health Organization (WHO) grade 2 (neutropenia). No patient had a complete or partial response, two patients had a minor response, two patients had stable disease and 11 patients had disease progression. CONCLUSIONS: Subcutaneous r-IL2 and IFN-alpha had no beneficial effect on the first 15 patients and the study was discontinued, in accordance with the Fleming rules. The dose, administration and combination of r-IL2 and IFN-alpha may explain the lack of efficacy. Other studies have shown that low doses of r-IL2 are not effective and the superiority of the combination of r-IL2 and IFN-alpha has not been proven. Therefore, a high dose of r-IL2, in association with other cytokines, chemotherapy and adoptive immunotherapy, may be the only way to improve the response rate of metastatic RCC.