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Production of tumor necrosis factor α and interferon γ in interleukin-2-treated melanoma patients: Correlation with clinical toxicity

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Summary

Interleukin-2 (IL-2)-based immunotherapy regimens are accompanied by dose-limiting toxicity consisting of fever, tachycardia, chills and capillary leak syndrome. We hypothesized that the toxicity was caused by the induction and release of endogenous cytokines such as tumor necrosis factor α (TNFα) and interferon γ (IFNγ). We measured the serum levels of TNFα and IFNγ in IL-2-treated melanoma patients and attempted a correlation with clinical toxicity. A total of 23 patients received either 6 × 106 IU or 12 × 106 IU Cetus IL-2/m2 by i. v. bolus daily for 5 consecutive days on weeks 1, 3 and 5. Serum TNFα and IFNγ levels were measured by enzyme-linked immunosorbent assay. Clinical toxicity was scored each day by objective measurements of hypotension, tachycardia, fever and chills/rigors. Clinical toxicity and IFNγ levels correlated nicely, peaking on the 5th day of each treatment cycle. The kinetics and magnitude of TNFα production, however, were not predictable and did not correlate with either IFNγ or toxicity. Some patients had modest increases in TNFα production while others had markedly increased levels during the second and third treatment weeks. Remarkably, these high levels persisted during nontreatment weeks and after completion of therapy. This clinical study demonstrates novel kinetics for immunoreactive TNFα in IL-2 cancer patients, which do not correlate well with toxicity.

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Authors and Affiliations

  1. Division of Surgical Oncology, Department of Surgery, John Wayne Cancer Clinic, University of California, Los Angeles Medical Center, 10833 LeConte Avenue, 90024-1782, Los Angeles, CA, USA

    James S. Economou, Mary Hoban, Jeffrey D. Lee, Richard Essner, Stephen Swisher, Dave B. Hoon & Donald L. Morton

  2. Department of Radiation Oncology, Jonsson Comprehensive Cancer Center, University of California, Los Angeles Medical Center, 10833 LeConte Avenue, 90024-1782, Los Angeles, CA, USA

    William McBride

Authors
  1. James S. Economou
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  2. Mary Hoban
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  3. Jeffrey D. Lee
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  4. Richard Essner
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  5. Stephen Swisher
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  6. William McBride
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  7. Dave B. Hoon
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  8. Donald L. Morton
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Additional information

This work was supported by NIH Grants CA 50 780 (J. E.) and CA 29 605, CA 12 582 (D. L. M.) and the U. C. Tobacco-Related Disease Research Program RT-62 (J. E.). J. E. is the recipient of an NCI Clinical Investigator Award (KO8-01360) and is a Dorothy and Leonard Straus Scholar at UCLA

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Economou, J.S., Hoban, M., Lee, J.D. et al. Production of tumor necrosis factor α and interferon γ in interleukin-2-treated melanoma patients: Correlation with clinical toxicity. Cancer Immunol Immunother 34, 49–52 (1991). https://doi.org/10.1007/BF01741324

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  • DOI: https://doi.org/10.1007/BF01741324

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