A clinical investigation trial to analyze the role of interleukin-2 in the treatment of patients with cancer has been designed. This trial tests the toxicity of recombinant interleukin-2 preparations given subcutaneously, intramuscularly, or by slow intravenous infusion in escalating doses. Concomitantly, we are studying the pharmacokinetics and immunomodulatory dose properties of recombinant interleukin-2 when given by these routes in escalating doses. Finally, in an attempt to evaluate the possible antitumor effects of interleukin-2 in cancer patients, we administer the agent for three weeks on a daily basis at the optimal immunomodulatory dose (as determined by our in vitro immunomonitoring assays). Fourteen patients have been entered on study to date of whom 13 are evaluable. No tumor responses have been seen with six having stable disease and seven having progressive disease. At doses through 10-6 units/m2 toxicities were mild and consisted of diarrhea, fatigue, rash, pruritus, and fever which were easily controlled symptomatically and promptly resolved after therapy was stopped. At 10-7/m2, patients developed fluid retention, hypotension, decreased urine output, and anxiety. There was one death at 10-7/m2, but it is not yet known whether this was treatment related or due to the patient's underlying disease.
