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

Abstract

Interleukin 1 alpha (IL-1 alpha) 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-1 alpha (rhIL-1 alpha) in 17 patients with refractory malignancies to examine its toxicity and biologic activity. rhIL-1 alpha 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 micrograms/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 micrograms/m2. rhIL-1 alpha induced a significant increase in absolute neutrophil count over baseline (p < 0.05), a 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-gamma-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-1 alpha administration is well tolerated at a dose of 2.0 micrograms/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-gamma-mediated MCCTX.

• Authors: M A Rosenthal, D Dennis, L Liebes, P Furmanski, D Caron, L Garrison, J Wiprovnick, D Peace, R Oratz, J Speyer, A Chachoua
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) Vol. 21 Issue 5 Pg. 371-8 (Sep 1998) ISSN: 1524-9557 [Print] United States
• PMID: 9789199 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article)

Chemical References

• Cytokines
• Interleukin-1
• Recombinant Proteins

Topics

• Adult
• Aged
• Bone Marrow (drug effects)
• Cytokines (analysis)
• Cytotoxicity, Immunologic (drug effects)
• Female
• Hematopoietic Stem Cells (drug effects)
• Humans
• Immunophenotyping
• Infusions, Intravenous
• Interleukin-1 (administration & dosage, adverse effects, therapeutic use)
• Lymphocyte Subsets (drug effects)
• Male
• Middle Aged
• Monocytes (drug effects)
• Neoplasms (drug therapy, immunology)
• Recombinant Proteins
• Safety