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High-dose continuous venous infusion of interleukin-2: Influence of dose and infusion rate on tumoricidal function and lymphocyte subsets

  • Original Article
  • Interleukin-2, Tumoricidal Function, Lymphocytes, Dose-Response, Clinical Trial
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

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Abstract

Previous clinical studies have demonstrated a dose-response relationship between enhancement of certain immune parameters and interleukin-2 (IL-2) dose in trials with low dosages of the cytokine. This has not been demonstrated for high-dose (greater than 18×106 IU/m2 per day) IL-2. We completed phase II trials of sustained administration of indomethacin and ranitidine with IL-2 given as a continuous infusion over 5 days for three courses. Peripheral blood mononuclear cells, both fresh and cultured in vitro with IL-2 or IL-2 and indomethacin, were tested for tumoricidal function against K562 and Daudi targets; these results were then correlated with actual delivered dose and mean infusion rate per course. Similar correlations were calculated between delivered dose or infusion rate and absolute and proportional counts of lymphocyte subsets as determined by flow cytometry. No enhancement of in vitro tumoricidal function with either increasing delivered dose or increasing infusion rate was seen. No consistent pattern of correlation was found between the absolute counts of lymphocyte subsets after each course of IL-2 with delivered dose or infusion rate. The percent rise in absolute counts of selected T- and NK-cell subsets at the end of course 1 compared with baseline values correlated positively with infusion rate; however, a similar correlation between the infusion rate and an increase in lymphocyte tumoricidal function was lacking. Little evidence was found for improved tumoricidal function of mononuclear cells or consistent enhancement of lymphocyte subset counts in patients able to tolerate doses of IL-2 beyond 18×106 IU/m2 per day in a 5-day continuous infusion schedule.

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Author notes

  1. Wilson C. Mertens

    Present address: Division of Hematology and Oncology, Wayne State University School of Medicine, 520 Hudson, Harper Hospital, 3990 John R, 48201, Detroit, MI, USA

Authors and Affiliations

  1. Department of Medical Oncology, London Regional Cancer Centre, London, Ontario, Canada

    Wilson C. Mertens & Vivien H. C. Bramwell

  2. Department of Pathology, St. Joseph's Health Centre, London, Ontario, Canada

    Diponkar Banerjee

  3. Department of Oncology, University of Western Ontario, London, Ontario, Canada

    Wilson C. Mertens, Vivien H. C. Bramwell & Peeyush K. Lala

  4. Department of Pathology, University of Western Ontario, London, Ontario, Canada

    Diponkar Banerjee

  5. Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada

    Larry Stitt

  6. Department of Anatomy, University of Western Ontario, London, Ontario, Canada

    Nahla Al-Mutter & Peeyush K. Lala

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Mertens, W.C., Banerjee, D., Al-Mutter, N. et al. High-dose continuous venous infusion of interleukin-2: Influence of dose and infusion rate on tumoricidal function and lymphocyte subsets. Cancer Immunol Immunother 41, 271–279 (1995). https://doi.org/10.1007/BF01517214

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  • DOI: https://doi.org/10.1007/BF01517214

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