LACK OF EFFICACY OF LOW-DOSE SUBCUTANEOUS RECOMBINANT INTERLEUKIN-2 AND INTERFERON-ALPHA IN THE TREATMENT OF METASTATIC RENAL-CELL CARCINOMA

Objective To evaluate the efficacy and toxicity of subcutaneous immuno therapy using a combination of recombinant interleukin-2 (r-IL2) and i nterferon-alpha (IFN-alpha) for the treatment of patients with metasta tic renal cell carcinoma (RCC). Patients and methods Initially a maxim um 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 adv anced RCC, 15 patients were included in the study (10 men and Eve wome n, 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, I FN-alpha was given three times a week for the last 5 weeks. Minimum fo llow-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 th e first 5 days of treatment. Overall, 80% of the patients received mor e than 75% of the complete dose of r-IL2. One patient suffered toxicit y greater than the World Health Organization (WHO) grade 2. (neutropen ia), No patient had a complete or partial response, two patients had a minor response, two patients had stable disease and 11 patients had d isease progression. Conclusions Subcutaneous r-IL2 and IFN-alpha had n o beneficial effect on the first 15 patients and the study was discont inued, in accordance with the Fleming rules, The dose, administration and combination of r-IL2 and IFN-alpha may explain the lack of efficac y. 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 Ethe r cytokines, chemotherapy and adoptive immunotherapy, may be the only way to improve the response rate of metastatic RCC.