PHASE-I TRIAL OF COMBINED RECOMBINANT INTERLEUKIN-2 WITH LEVAMISOLE IN PATIENTS WITH ADVANCED MALIGNANT DISEASE

A Phase I study of rIL-2 and levamisole was Performed to evaluate the activity, toxicity, and effect on immune parameters of this combinatio n of agents in patients with advanced malignancy. Twelve patients with advanced cancer were included and begun on therapy with rIL-2, 1 X 10 (6) U/M2 subcutaneously (SQ) daily for 5 days and levamisole beginning at 25 Mg/M2 orally three times daily for 5 days. The dose of levamiso le was increased to 50 Mg/M2 thrice daily during this study. Immune pa rameter analysis included the percentages of lymphocyte subsets in per ipheral blood, cellular cytotoxicity assays versus K562 and Daudi cell s, and lymphocyte blastogenesis to the recall antigens tetanus toxoid and Candida albicans. The dose-limiting toxicities were pruritus, naus ea, and facial edema. There were no indications of significant hematol ogic or hepatorenal toxicities. No patient fulfilled the traditional c riteria for an objective response. In 8 of 9 patients with immune para meter data available there was an increase in cellular cytotoxicity an d in the percentage of lymphocytes with the natural killer phenotype ( CD3-, CD16/56+). This regimen can be given as an outpatient with accep table toxicity. For Phase 11 investigations the doses of rIL-2, 1 X 10 (6) U/M2 SQ daily X 5 days and levamisole, 50 mg/m2 three times daily x 5 days is recommended.