Phase 1 trial of recombinant human interleukin-1 beta (rhIL-1 beta), carboplatin, and etoposide in patients with solid cancers: Southwest Oncology, Group Study 8940.

Recombinant human interleukin-1 beta (rhIL-1 beta) was evaluated in a phase 1 clinical trial in which patients with metastatic or unresectable solid tumors received carboplatin and etoposide in cycle 1 and carboplatin, etoposide, and rhIL-1 beta in cycle 2. Recombinant hIL-1 beta was given intravenously for 5 days in one of three schedules: (1) immediately postchemotherapy, (2) delayed for 5 days after chemotherapy, or (3) concurrently with chemotherapy. Four dose levels of rhIL-1 beta were evaluated: 20, 50, 100, and 200 ng/kg. The doses of carboplatin and etoposide were not changed between cycle 1 and cycle 2 so that the effect of rhIL-1 beta on chemotherapy-induced hemato-toxicity was evaluated; 54 patients were entered on study and 42 patients received at least two cycles of therapy and were thus evaluable for rhIL-1 beta toxicity and for the effect of rhIL-1 beta on hematotoxicity of carboplatin and etoposide. The major toxicities of rhIL-1 beta were chills, rigors, headache, fatigue, and hypotension. The maximum tolerated dose of rhIL-1 beta was not determined since the toxicities at all dose levels were similar. However, only 3/8 patients at the 200 ng/kg level received all 5 IL-1 beta infusions. We compared the effect of rhIL-1 beta on hematotoxicity of carboplatin/etoposide by comparing peripheral blood count parameters between cycles 1 and 2: rhIL-1 beta given postchemotherapy significantly increased absolute neutrophil count (AND) nadirs and improved neutrophil recovery times regardless of rhIL-1 beta dose level. Platelet count parameters were also improved when rhIL-1 beta was given postchemotherapy although these changes did not reach statistical significance. Thus, IL-1 beta exhibited extensive hematological effects but the usefulness of this agent in clinical practice will be limited by extensive toxicity at all tested dose levels.