This trial was designed to evaluate the immunomodulatory effects and toxic effects of interleukin-2 in patients with cancer. The interleukin-2 was given subcutaneously, intramuscularly, or by slow intravenous infusion for 24 hours in single escalating doses given once per week. The pharmacokinetics of IL-2 and the effects of the IL-2 on various immune parameters were monitored serially. Each individual patient then received daily intramuscularly injections of interleukin-2 for 5 consecutive days for 3 consecutive weeks. The dose of interleukin-2 used during this 3-week period was that dose which optimally augmented the immune function during the initial dose-escalation phase of the study. Thirteen patients are evaluable for response and toxicity on this trial. No tumor responses were seen. Single doses of interleukin- 2 were incapable of significantly augmenting immune function even with doses up to 3 times 10 to the 7th units per meter squared. When patients received daily injections of interleukin-2, significant alterations in immune function were observed. There were persisting and progressive elevations in the soluble IL-2 receptor level, natural killer cell activity in the peripheral blood, and the appearance of Leu-19 positive cells in the peripheral blood. These changes were progressive over time but returned to baseline within 4 weeks. Based upon these favorable effects on the immune system, interleukin-2 is being administered in a new trial at moderate dosages for prolonged periods of time.
