Abstract

Interleukin-1 alpha (IL-1 alpha) is myeloprotective in a variety of animal models of cancer chemotherapy and is similarly beneficial in adults treated with carboplatin, 5-fluorouracil, and after autologous bone marrow transplantation. There are no trials of this agent in children. Our purpose was to determine the toxicity and maximum tolerated dose (MTD) of recombinant human interleukin-1 alpha (rhuIL-1 alpha) in children with solid tumors receiving intensive cancer chemotherapy and to evaluate its myelo-protective effects. Cohorts of patients received rhuIL-1 alpha in doses of 0.1-10 micrograms/m2 for 4 days by subcutaneous injection prior to ICF chemotherapy (ifosfamide, 2 g/m2/day x 3, carboplatin targeted to an area under the curve of 8 mg/ml x min on day 1, and etoposide, 100 mg/m2 daily for 3 days). Patients were randomized to receive rhuIL-1 alpha before either the first or second course of therapy. After the MTD of rhuIL-1 alpha was determined an additional group of patients received rhuIL-1 alpha at the dose immediately following ICE chemotherapy. The dose-limiting toxicities of rhuIL-1 alpha in the 27 children tested comprised systemic symptoms of fever, chills, headache, and hypotension. The MTD was 3 micrograms/m2/day. There were no differences in chemotherapy-induced hematologic toxicity with increasing doses of rhuIL-1 alpha or in comparisons before or after ICE chemotherapy. Although rhuIL-1 alpha can be given safely to children receiving myelosuppressive chemotherapy, clinical usefulness would mandate a significant hematopoietic benefit in view of the trouble some side effects identified. We saw no evidence of a hematoprotective effect.

View details for Web of Science ID A1997WX01300010

View details for PubMedID 9143391