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A phase I study of human lymphoblastoid interferon administered by continuous intravenous infusion

  • Original Articles
  • Interferon Phase I Study
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Summary

A phase I study of human lymphoblastoid interferon (IFN-α) was undertaken in patients with acute leukaemia and other malignancies. The pharmacokinetics of intravenous IFN-α were also investigated.

IFN-α was administered to two patients by intravenous (IV) bolus injection at a dose of 5×106 U/m2; and to a further 37 patients (40 cycles) by continuous intravenous infusion (IVI) for 5, 7, or 10 days at doses ranging from 5 to 200×106 U/m2/day. Pyrexia, general malaise, anorexia, and rigors were observed at all dose levels; three patients became hypotensive. Myelosuppression occurred in all patients, including seven without bone marrow infiltration. Transient rises in alkaline phosphatase and transaminases (SGOT) were observed in patients receiving daily doses greater than 30×106 U/m2. Dose-limiting central nervous system toxicity, hyperkalaemia, and hypocalcaemia were encountered at 200×106 U/m2.

In six patients with acute leukaemia there was a fall in the number of circulating leukaemic blasts and in one patient with acute myelogenous leukaemia (AML) the degree of bone marrow infiltration decreased from 99% to less than 5% with cellularity returning to normal. Serum levels of IFN above 1,000 U/ml were achieved with daily doses above 30×106 U/m2 given by IVI. The maximum safely tolerated daily dose, 100×106 U/m2 administered for 7 days, is appreciably higher than that used in most previous studies, although even at this level consideralbe toxicity may be encountered.

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References

  1. Balkwill FR (1979) Interferons as cell-regulatory molecules. Cancer Immunol Immunother 7:7–14

    Google Scholar 

  2. Balkwill F, Oliver RTD (1977) Growth inhibitory effect of interferon on normal and malignant human haemopoeitic cells. Int J Cancer 20:500–505

    Google Scholar 

  3. Christofinis JG (1971) Biological characteristics of a cell line GL-V3 derived from the kidney of a vervet monkey:Ceropithecus aethiops. J Med Microbiol 3:251–258

    Google Scholar 

  4. Emodi G, Just M, Hernandez R, Hirt HR (1975) Circulating interferon in man after administration of exogenous human leukocyte interferon. J Natl Cancer Inst 54:1045–1049

    Google Scholar 

  5. Greenberg HB, Pollard RB, Lutwick LI, Gregory PB, Robinson WS, Merigan TC (1976) Effect of human leukocyte interferon on hepatitis B virus infection in patients with chronic active hepatitis. N Engl J Med 295:517–522

    Google Scholar 

  6. Gresser I, Brouty-Boye D, Thomas M-I, Macieira-Coelho A (1970) Interferon and cell division. I. Inhibition of the multiplication of mouse leukaemia L 1210 cells in vitro by interferon-preparations. Proc Natl Acad Sci USA 66:1052

    Google Scholar 

  7. Grollman EF, Lee G, Ramos S, Lazo PS, Kaback HR, Friedman RM, Kohn LD (1978) Relationships of the structure and function of the interferon receptor to hormone receptors and establishment of the antiviral state. Cancer Res 38:4172–4175

    Google Scholar 

  8. Gutterman JU, Blumenschein GR, Alexanian R, Yap H-Y, Buzdar AU, Cabanillas F, Hortobagyi GN, Hersh EM, Rasmussen SL, Harmon M, Kramer M, Pestka S (1980) Leukocyte interferon-induced tumor regression in human metastatic breast cancer, multiple myeloma and malignant lymphoma. Ann Intern Med 93:388–406

    Google Scholar 

  9. Hill NO, Loeb E, Pardue A, Khan A, Dorn GL, Comparini S, Hill JM (1978) Leukocyte interferon production and its effectiveness in acute lymphatic leukaemia. J Clin Hematol Oncol 8:67–82

    Google Scholar 

  10. Hill NO, Pardue A, Khan A, Aleman D, Hill JM (1981) High-dose human leukocyte interferon trials in leukemia and cancer. Med Pediatr Oncol 9:1

    Google Scholar 

  11. Horning SJ, Levine JF, Miller RA, Merigan TC (1982) Clinical and immunologic effects of recombinant leukocyte A interferon in eight patients with advanced cancer. Lancet (in press)

  12. Ingimarsson S, Cantell K, Strander H (1979) Side effects of long-term treatment with human leukocyte interferon. J Infect Dis 140:560–563

    Google Scholar 

  13. Isaacs A, Lindenmann J (1975) Virus interference. I. The interferon. Proc R Soc Lond [B] 147:258–267

    Google Scholar 

  14. Karanes C, Wolfe SN, Herzig GP, Phillips GL, Lazarus HM, Herzig RH (1979) High-dose cytosine arabinoside (AraC) in the treatment of patients with acute non-lymphocytic leukaemia (ANLL). Blood Abstracts 504:191a

    Google Scholar 

  15. Levine AS, Levy HB (1978) Phase I–II trials of poly IC stabilized with poly-l-lysine. Cancer Treat Rep 62:1907–1912

    Google Scholar 

  16. Louie AC, Gallagher JG, Sikora K, Levy R, Rosenberg SA, Merigan TC (1981) Follow-up observations on the effect of human leukocyte interferon in non-Hodgkin's lymphoma. Blood 58:712–718

    Google Scholar 

  17. Lundgren E, Hillörn W, Holmberg D, Lenner P, Roos G (1980) Comparative study on the effects of fibroblast and leukocyte interferon on short term cultures of leukemic cells. Ann NY Acad Sci 350:628

    Google Scholar 

  18. Mellstedt H, Bjorkholm M, Johansson B, Ahre A, Holm G, Strander H (1979) Interferon therapy in myelomatosis. Lancet I:245–247

    Google Scholar 

  19. Merigan TC (1977) Pharmacokinetics and side effects of interferon in man. Tex Rep Biol Med 35:541–547

    Google Scholar 

  20. Priestman TJ (1980) Initial evaluation of human lymphoblastoid interferon inpatients with advanced malignant disease. Lancet II:113–118

    Google Scholar 

  21. Rohatiner AZS, Balkwill F, Malpas JS, Lister TA (1981) A Phase I study of human lymphoblastoid interferon in patients with haematological malignancies. In: Modern trends in human leukaemia, vol IV. Springer, Berlin Heidelberg New York, pp 63–67

    Google Scholar 

  22. Salazar AM, Gibbs CJ, Gajdusek DC, Smith RA (1982) Clinical usage of interferons in central nervous system disorders. In: Came P, Carter W (eds) Interferons and their applications. Springer, Berlin Heidelberg New York, (in press)

    Google Scholar 

  23. Scott GM, Secher DS, Flowers D, Bate J, Cantell K, Tyrell DAJ (1981) Toxicity of interferon. Br Med J 282:1345–1348

    Google Scholar 

  24. Strander H, Cantell K, Carlstrom G, Jakobsson PA (1973) Clinical and laboratory investigations on man: systemic administration of potent interferon to man. J Natl Cancer Inst 5:733–742

    Google Scholar 

  25. Taetle R, Buick RN, McCulloch EA (1980) Effect of interferon on colony formation in culture by blast cell progenitors in acute myeloblastic leukaemia. Blood 56:549–552

    Google Scholar 

  26. Taylor-Papadimitriou J (1980) Effects of interferons on cell growth and function. In: Interferon II, 13–46

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Authors and Affiliations

  1. I.C.R.F. Department of Medical Oncology, St. Bartholomew's Hospital, West Smithfield, EC1A, 7 BE, London

    A. Z. S. Rohatiner, J. S. Malpas & T. A. Lister

  2. I.C.R.F. Laboratories, Queen Square, WC1, London, Great Britain

    F. R. Balkwill & D. B. Griffin

Authors
  1. A. Z. S. Rohatiner
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  2. F. R. Balkwill
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  3. D. B. Griffin
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  4. J. S. Malpas
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  5. T. A. Lister
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Rohatiner, A.Z.S., Balkwill, F.R., Griffin, D.B. et al. A phase I study of human lymphoblastoid interferon administered by continuous intravenous infusion. Cancer Chemother. Pharmacol. 9, 97–102 (1982). https://doi.org/10.1007/BF00265387

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  • DOI: https://doi.org/10.1007/BF00265387

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