title: The toxic and hematologic effects of interleukin-1 alpha administered in a phase I trial to patients with advanced malignancies.
abstract: OBJECTIVE
  A phase I trial was undertaken because interleukin-1 alpha (IL-1 alpha) possesses antiproliferative, immunostimulatory, antiinfection, myeloprotective, and myelorestorative properties that could be beneficial in cancer treatment.
  
  
  METHODS
  In this phase I trial, IL-1 alpha was administered intravenously (IV) during a 15-minute period daily for 7 days to patients with advanced solid malignancies.
  
  
  RESULTS
  The maximum-tolerated dose (MTD) of IL-1 alpha alone was 0.3 microgram/kg. A second group of patients received indomethacin plus IL-1 alpha based on preclinical studies, which indicated that indomethacin could abrogate IL-1 alpha-induced hypotension; however, the MTD of IL-1 alpha plus indomethacin was 0.1 microgram/kg lower than IL-1 alpha alone. Fever, chills, headache, nausea, vomiting, and myalgia were common but were not dose-limiting. Hypotension resulted from a marked decrease in systemic vascular resistance and required pressors at 0.3 and 1.0 micrograms/kg IL-1 alpha. Dose-limiting toxicities included hypotension, myocardial infarction, confusion, severe abdominal pain, and renal insufficiency. IL-1 alpha treatment caused a significant, dose-related increase in the total WBC count (mainly segmented neutrophils and neutrophilic bands). Bone marrow cellularity increased because of enhanced numbers of relatively mature myeloid cells and megakaryocytes. Platelet counts decreased during therapy but were significantly elevated above baseline values 1 to 2 weeks posttreatment; this may have been an effect of IL-6 that was shown to be induced by IL-1 alpha treatment. Significant increases in triglycerides, cortisol, C-reactive protein, thyroid-stimulating hormone and decreases in cholesterol, testosterone, and protein-C were observed with treatment.
  
  
  CONCLUSIONS
  We conclude that at doses of IL-1 alpha that can be given safely to cancer patients, significant, potentially beneficial hematopoietic effects occur.
authors.affiliation: Biological Response Modifiers Program, Frederick Memorial Hospital, MD.
authors.forename: J W
authors.initials: JW
authors.lastname: Smith
authors.forename: W J
authors.initials: WJ
authors.lastname: Urba
authors.forename: B D
authors.initials: BD
authors.lastname: Curti
authors.forename: L J
authors.initials: LJ
authors.lastname: Elwood
authors.forename: R G
authors.initials: RG
authors.lastname: Steis
authors.forename: J E
authors.initials: JE
authors.lastname: Janik
authors.forename: W H
authors.initials: WH
authors.lastname: Sharfman
authors.forename: L L
authors.initials: LL
authors.lastname: Miller
authors.forename: R G
authors.initials: RG
authors.lastname: Fenton
authors.forename: K C
authors.initials: KC
authors.lastname: Conlon
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001773:Blood Cells / Q000187:drug effects*; D001853:Bone Marrow / Q000187:drug effects; D004341:Drug Evaluation; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*
chemical_list: D007375:Interleukin-1; D007213:Indomethacin