Interleukin-1 (IL-1) plays a central role in immune responses and might be useful in the treatment of cancer patients for several reasons. We conducted a phase I clinical trial of IL-1 alpha to determine the: (1) toxicity of IL-1 in cancer patients, (2) effects of IL-1 in the immune system, (3) effects of IL-1 on the hemopoietic system, (4) pharmacokinetics of IL-1 and (5) the effect of adding indomethacin on all of the above. All patients had chills, fever, headache, and some had nausea, vomiting, myalgia, arthralgia, and abdominal pain. Hypotension, renal insufficiency, confusion, and abdominal pain were the dose-limiting toxicities. The inpatient-maximum tolerated dose (MTD) of IL-1 alpha administered alone with blood pressure support was determined to be 0.3 mog/kg. With the addition of indomethacin at 25 mg every 8 hours, the maximum tolerated dose was determined to be 0.1 mog/kg. IL-1 alpha did not cause an increase in peripheral blood natural killer cell and lymphokine activated killer cell activity. However, IL-1 treatment did induce increases in serum soluble IL-2 receptor levels and in IL-6 levels. Pharmacokinetic studies indicated measurable IL-1 alpha levels at the two highest dose levels consistent with a short alpha half-life of 10-15 minutes. IL-1 caused a dose related 2-7 fold increase in the white blood count (mainly increased neutrophils and neutrophil bands). The platelet count declined slightly during treatment but increased one and a half to two times above baseline one week later in five patients studied at that time. Bone marrow aspirates one day after the end of treatment showed increased cellularity and increased M/E ratio compared to ones obtained before treatment.
