Phase 1 Trial of Recombinant Human Interleukin-1β (rhIL-1β), Carboplatin, and Etoposide in Patients with Solid Cancers: Southwest Oncology Group Study 8940

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Abstract
Recombinant human interleukin-1β (rhIL-1β) 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-1β in cycle 2. Recombinant hIL-1β 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-1β 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 ofrhlL-1β on chemotherapy-induced hematotoxicity was evaluated; 54 patients were entered on study and 42 patients received at least two cycles of therapy and were thus evaluablefor rhIL-1β toxicity and for the effect ofrhIL-1β on hematotoxicity of carboplatin andetoposide. The major toxicities of rhIL-1β were chills, rigors, headache, fatigue, and hypotension. The maximum tolerated dose of rhIL-1β 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-1β infusions. We compared the effect of rhIL-1β on hematotoxicity of carboplatin/etoposide by comparing peripheral blood count parameters between cycles 1 and 2: rhIL-1β given postchemotherapy significantly increased absolute neutrophil count (AND) nadirs and improved neutrophil recovery times regardless ofrhIL-1β dose level. Platelet count parameters were also improved when rhIL-1β was given postchemotherapy although these changes did not reach statistical significance. Thus, IL-1β exhibited extensive hematological effects but the usefulness of this agent in clinical practice will be limited by extensive toxicity at all tested dose levels.