Biologic activity of interleukin 1 (IL-1) alpha in patients with refractory malignancies

Mark A. Rosenthal, David Dennis, Leonard Liebes, Phil Furmanski, Dania Caron, Leslie Garrison, Jay Wiprovnick, Denise Peace, Ruth Oratz, James Speyer, Abraham Chachoua

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Interleukin Iα (IL-Iα) is a cytokine with pleiotropic effects, including cytotoxic-cytostatic activity against some tumor cell lines. We have conducted a phase I study of recombinant human IL-Iα (rhIL-Iα) in 17 patients with refractory malignancies to examine its toxicity and biologic activity. rhIL-Iα was given as a 2-h IV infusion daily for 5 days at five dose levels (0.08, 0.2, 0.8, 2.0, and 5.0 µg/m2). Seventeen patients with malignancies were treated, with no objective tumor responses noted. Common toxicities included: fever (100%), rigors and/or chills (96%), myalgia (54%), and headache (48%). Three patients developed grade III hypotension. The maximum tolerated dose was 2.0 µg/m2. rhIL-Iα induced a significant increase in absolute neutrophil count over baseline (p < 0.05), and delayed but significant increase in platelet count over baseline (p < 0.05), and there was a marked increase in the number of progenitors [colony-forming units (CFU)-G, CFU-M, CFU-GM, CFU-GEMM and burst-forming units (BFU-E)] observed in the peripheral blood. Nine of 12 evaluable patients showed an increase in bone marrow cellularity or myeloid:erthyroid ratio. Immunophenotyping did not demonstrate an increase in peripheral blood or bone marrow CD34+ cells. Interferon-γ-mediated monocyte cytotoxicity (MCCTX) was significantly enhanced from baseline (p < 0.001), although an increase in direct MCCTX did not reach statistical significance. In summary. rhIL-Iα administration is well tolerated at a close of 2.0 µg/m2 with fever, rigors, myalgia, and headache being the most frequent toxicities. Although there were no objective tumor responses, we have demonstrated significant biologic activity with increased neutrophil and platelet counts, increased peripheral blood progenitor cells, and enhanced interferon-γ-mediated MCCTX.

Original languageEnglish (US)
Pages (from-to)371-378
Number of pages8
JournalJournal of Immunotherapy
Volume21
Issue number5
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

Keywords

  • IL-Iα
  • Malignancy
  • Phase I
  • Toxicity

Fingerprint Dive into the research topics of 'Biologic activity of interleukin 1 (IL-1) alpha in patients with refractory malignancies'. Together they form a unique fingerprint.

Cite this