title: Report of a phase I evaluation of dose and schedule of interleukin-1 alpha and cyclophosphamide in patients with advanced tumors: An Eastern Cooperative Oncology Group study (PX990) and review of IL-1-based studies of hematopoietic reconstitution.
abstract: Interleukin-1 (IL-1) is a cytokine critical to inflammation, immunological activation, response to infection, and bone marrow hematopoiesis. Cyclophosphamide downmodulates immune suppressor cells and is cytotoxic to a variety of tumors. A phase I trial of IL-1 and cyclophosphamide was conducted by the Eastern Cooperative Oncology Group. This study evaluated 3 dose levels and 3 schedules in patients with solid tumors. The goal was to evaluate the hematopoietic supportive care effect and possible antitumor effect. Toxicity was fever, chills, hypotension, nausea/emesis, hepatic, and neutropenia. Toxicity increased with dose increases of interleukin-1. Treatment at all dose levels resulted in significant increases in total white blood cell (WBC) counts above baseline. Nadir WBC and nadir absolute neutrophil counts were not significantly different by dose level of IL-1 or schedule of IL-1. Toxicity due to IL-1 at higher doses prohibited further evaluation of this agent for hematopoietic support, particularly in view of the activity and tolerability of more lineage-specific hematopoietic cytokines. Therapeutic interventions in the role of IL-1 in inflammatory conditions and cancer may be further informed by our definition of its clinical and biological effects in this evaluation of dose and schedule.
authors.affiliation: 1 Department of Oncology, Montefiore Medical Center , Bronx, New York.
authors.forename: Janice P
authors.initials: JP
authors.lastname: Dutcher
authors.forename: Donna
authors.initials: D
authors.lastname: Neuberg
authors.forename: Michael B
authors.initials: MB
authors.lastname: Atkins
authors.forename: William J
authors.initials: WJ
authors.lastname: Tester
authors.forename: Scott
authors.initials: S
authors.lastname: Wadler
authors.forename: James A
authors.initials: JA
authors.lastname: Stewart
authors.forename: Abraham
authors.initials: A
authors.lastname: Chachoua
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Schuchter
mesh_terms: D000328:Adult; D000368:Aged; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D053582:Interleukin-1alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D014184:Transplantation, Homologous
chemical_list: D053582:Interleukin-1alpha; D003520:Cyclophosphamide