Anti-tumor effects of interleukin 2 against genitourinary cancer--basic study and clinical application

In order to establish an optimum mode for systemic administration of recombinant interleukin 2 (rIL-2), the effects of rIL-2 (Biogen, Switzerland) on lymphocyte-mediated cytotoxicity against established renal carcinoma cell line Caki 1. KU-2 and freshly prepared renal carcinoma cells were studied. Augmentation of cell-mediated cytotoxicity by rIL-2 was dose- and time-dependent. The results indicated that the optimal dose of rIL-2 was 100 to 500 units (Jurkat units)/ml, and that cytotoxicity increased significantly even at a low concentration such as 4 units/ml. We thus chose daily administration of multiple repeated dose for inpatients. To prevent withdrawal from the therapy as a result of un-tolerable adverse effects, the daily dose was set at 1 x 10(6) units, and rIL-2 was given to 17 patients with advanced genitourinary cancer. Two-hour intravenous drip infusions containing 5 x 10(5) units of rIL-2 was given daily two times to inpatients and after at least 28 days of this mode of administration, subcutaneous injection at a dose of 1 x 10(6) units was given 6 days a week to outpatients. In 12 patients with renal cell carcinoma, 2 patients showed complete response; 1 patient partial response; 7 patients no change, and 2 patients progressive disease. In patients with carcinoma of the prostate or bladder carcinoma, all patients were no change from criteria of Japan Society for Cancer Therapy, however, marked decrease in serum acid-phosphatase and improvement of performance status in 1 patient with carcinoma of the prostate, and massive necrosis of tumor accompanied by disappearance of severe leg edema in a patient with bladder carcinoma were observed.