A Direct Comparison of Immunological and Clinical Effects of Interleukin 2 with and without Interferon- in Humans1

Joan H. Schiller, Jacquelyn Hank, Barry Storer, Agnes A. Borchert, Karen Huseby Moore, Mark Albertini, Robin Bechhofer, Osvaldo Wesley, Raymond R. Brown, Ann Mrowca Bastin, Paul M. Sondel

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19 Scopus citations

Abstract

Interleukin 2 (IL-2) and interferon-a (IFN-a) are cytokines with synergistic antitumor effects in mouse models. The biological effects of this combination, however, have not been directly compared to each agent alone in humans. We conducted a Phase IB trial of IL-2 plus or minus IFN-a in 38 cancer patients. The objectives of this trial were to determine which doses of IFN-a and IL-2 maximally enhanced biological responses, and to determine whether the combined administration of IFN-a and IL-2 would result in a potentiation of biological responses over IL-2 alone. Patients received 4 days of IL-2 (L5 x 106 units/m2/day or 3.0 X 106 units/m2/day) as a continuous infusion followed by a 3-day rest period, weekly for 3 weeks, with a 3-week rest period between 2 treatment courses. IFN-a (0.5 x 106 or 5 x 106 units/m2/day) was administered sx. on days 1-4 weekly for 3 weeks with one of the 3-week courses. Patients were randomized to receive either IL-2 alone for course 1, followed by IL-2/ IFN-a for course 2, or IL-2/IFN-a in course 1, followed by IL-2 alone. Immunological parameters were evaluated before treatment, and 24 h after completion of the third week of IL-2.A statistically significant increase in the percentage of circulating natural killer cells (CD56), natural killer cells bearing the Fc receptor (CD16), and activated T cells (CD25) was observed following IL-2 alone, and following IL-2 plus IFN-a. Significant increases in lymphocyte-activated killer cell cytotoxicity, antibody cellular cytotoxicity, and serum IL-2 receptor were also observed following both IL-2 and IL-2 plus IFN-a. However, no significant differences were observed in the magnitude of the increase in the IL-2-alone group when compared to the IL-2 plus IFN-a group. The mean fluorescent intensity of monocytes positive for HLA-DR and Fc receptor expression also increased significantly in both groups, as did serum 2-microglobulin expression and indoleamine 2,3-dioxygenase activity. However, increases were not significantly different between patients receiving IL-2 alone and IL-2 plus IFN-a. No dose response effect for IFN-a was observed for any of the parameters assessed.Toxicities consisted primarily of constitutional toxicities, including fever, rigors, malaise, headache, anorexia, and a decrease in performance status. No clinically significant differences in toxicities were observed between courses consisting of IL-2 and those consisting of IFN-a and IL-2. Two patients had a partial response, and 5 patients had a minor response (partial plus minor response rate, 18%).In conclusion, we did not observe a difference in biological activity between IL-2 and IL-2 plus IFN-a in any of the immunological parameters we studied. Although this regimen was relatively well-tolerated, we cannot conclude that IFN-a adds significantly to the immunological or therapeutic activity of IL-2 alone.

Original languageEnglish (US)
Pages (from-to)1286-1292
Number of pages7
JournalCancer Research
Volume53
Issue number6
StatePublished - Mar 1993

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Schiller, J. H., Hank, J., Storer, B., Borchert, A. A., Moore, K. H., Albertini, M., Bechhofer, R., Wesley, O., Brown, R. R., Bastin, A. M., & Sondel, P. M. (1993). A Direct Comparison of Immunological and Clinical Effects of Interleukin 2 with and without Interferon- in Humans1. Cancer Research, 53(6), 1286-1292.