A phase I study of interleukin-2 in children with cancer.

Recombinant interleukin-2 (IL-2) produces clinical responses in approximately 20% of adult patients with renal cell carcinoma and melanoma, with both high-dose bolus and continuous infusion regimens. Because of the lower toxicity of continuous infusion, we elected to investigate in a Phase I trial a 5-day continuous infusion repeated for three weeks in children with malignancies refractory to standard therapy. Nineteen children with solid tumors and eight children with hematologic malignancies were entered into the study. The maximum tolerated dose was 3 x 10(6) U/m2/day, with dose-limiting toxicities occurring in five of seven patients treated at the 5 x 10(6) U/m2/day dose level. Dose-limiting toxicities included hypotension, hyperbilirubinemia, thrombocytopenia, pulmonary/pleural effusion, and nephrotoxicity. Serum IL-2 levels were detectable at the higher dose levels and were comparable to those observed in adult patients. Hematologic changes at the higher dose levels included rebound lymphocytosis occurring within 48 h of discontinuation of IL-2, eosinophilia, and decreased platelet counts. No objective responses to therapy were seen. We have identified a dose and schedule of administration for IL-2 in pediatric patients that can be given without intensive care unit support. Pediatric Phase II trials examining the anti-tumor activity of IL-2 given by this schedule are in progress.