The authors performed a Phase I study to assess the toxicity and hematologic effect of recombinant human interleukin-2 (rIL-2) in seven children with advanced malignancies. The rIL-2 was given as a bolus injection of 1 or 3 X lo6 U/m2/dose three times a week (Monday, Wednesday, and Friday) for 3 weeks. No life-threatening toxicity occurred with the dose of 1 X lo6 U/mZ of rIL-2. At a dose of 3 X lo6 U/mZ, therapy had to be terminated due to cardiovascular toxicity in two patients. Toxic effects at lowdose rIL-2 included fever, nausea, vomiting, and mild hypotension. High-dose rIL-2 toxicity included fluid retention, increased creatinine, oliguria, elevated liver enzymes, and significant hypotension. Immunologic studies showed that rIL-2 caused a drop in the number of circulating peripheral blood mononuclear cells, T-cells, and natural killer cells which returned to pretherapy levels or above by 24 to 48 hours. The rIL-2 exerted no growth or stimulatory activity on the leukemic cell population. To the authors' knowledge, this is the first report of a Phase I study of IL-2 therapy in children.
Cancer 64:783-788, 1989.
XPERIMENTAL STUDIES in animals and clinical trials E in human adults have demonstrated a potential role for interleukin-2 (IL-2) in the therapy of metastatic ma-lignan~ies.'-~ In humans, IL-2 immunotherapy appears to be most effective against melanomas and renal cell car-~i n o m a . ~. ~ These studies have not resolved basic problems which include the following: the amelioration of significant toxicity, the determination of optimal dose and mode of administration (continuous versus intermittent), the From the