Clinical effects and toxicity of interleukin‐2 in patients with cancer

Michael T. Lotze, Yvedt L. Matory, Anthony A. Rayner, Stephen E. Ettinghausen, John T. Vetto, Claudia A. Seipp, Steven A. Rosenberg

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    281 Scopus citations

    Abstract

    Interleukin‐2 (IL‐2) is a 15,000 dalton glycoprotein produced naturally by human T‐cells during an immune response. IL‐2 has been demonstrated to have substantial activity alone or in combination with the adoptive transfer of lymphokine‐activated killer cells in murine tumor models. IL‐2 derived from both natural (Jurkat human T‐cell tumor) and recombinant (Escherichia coli) sources has been studied in Phase I protocols designed to evaluate toxicity in patients with a variety of solid tumors and to ascertain improvement in clinical parameters and immunologic status. A total of 16 patients (7 with acquired immune deficiency syndrome [AIDS] and 9 with non‐AIDS malignancies) were treated with Jurkat derived IL‐2. The total maximum dose (1.3 × 105 U/kg) was limited only by supply of this reagent. A total of 25 patients have been treated with recombinant IL‐2 (RIL‐2) alone. Dose‐limiting toxicity manifested by marked malaise and weight gain was achieved with doses of RIL‐2 of 106 U/kg as a single bolus or 3000 U/kg/hr. IL‐2 could be administered intraperitoneally with similar toxicity. Minimal renal or hepatic toxicity was demonstrated. Hematologic toxicity was limited to mild anemia (25/25), thrombocytopenia (10/25), and marked reversible eosinophilia (15/25). Pronounced weight gain greater than 2 kg (16/25) occurred in most patients, primarily those who received cumulative doses of greater than 1–3 × 105 U/kg of IL‐2. The weight gain amounted to as much as 10% to 20% of the pretreatment weight over 3 weeks of treatment and limited our ability to give higher doses. Two partial responses (>50% decrease in cross sectional diameters) were seen in two patients with melanoma metastatic to the lung.

    Original languageEnglish (US)
    Pages (from-to)2764-2772
    Number of pages9
    JournalCancer
    Volume58
    Issue number12
    DOIs
    StatePublished - Dec 15 1986

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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  • Cite this

    Lotze, M. T., Matory, Y. L., Rayner, A. A., Ettinghausen, S. E., Vetto, J. T., Seipp, C. A., & Rosenberg, S. A. (1986). Clinical effects and toxicity of interleukin‐2 in patients with cancer. Cancer, 58(12), 2764-2772. https://doi.org/10.1002/1097-0142(19861215)58:12<2764::AID-CNCR2820581235>3.0.CO;2-Z