Skip to main content
Log in

Clinical effect of interferon in malignant brain tumours

  • Chemotherapy and immunotherapy of malignant gliomas
  • —A contribution by Japanese Neurosurgery—
  • Published:
Neurosurgical Review Aims and scope Submit manuscript

Summary

Phase I and phase II clinical studies of interferon (IFN) were conducted in malignant brain tumours (47 cases of glioblastoma, medulloblastoma and others) using three preparations of the drug. The drug was administered daily in doses 3.0 − 9.0 × 106 I.U. locally or intravenously (β-type) or intramuscularly (α-type). The administration was continued as many days as possible, eight weeks being the shortest period. The efficacy of the therapy was assessed mainly by the CT findings (computed volume of the tumour).

As for efficacy against glioblastomas, the highest effectiveness rate (40%) was obtained with Human Fibroblast IFN (HFIF) (β-type) (Toray) (one case of complete remission and seven cases of partial remission out of 20 cases) as compared to Human Lymphoblastoid IFN (HLBI) (αa-type) (Wellcome) (one case of partial remission out of three cases) and recombinant IFN (rIFN-αA) (α-type) (Roche) (two cases of partial remission out of nine cases). The high rate of responsiveness of HFIF seems to be largely attributable to the local, rather than systemic, administration of the drug. Our pharmacokinetic study revealed that, by means of intrathecal administration a much higher IFN titre was detected in the cerebrospinal fluid, while by intravenous or intramuscular route, the IFN titre in the CSF was undetectably low. The generally lower incidence of side-effects with HFIF compared to other preparations was also largely ascribable to the route of administration. IFN therapy in combination with radiotherapy and/or chemotherapy should also be investigated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Ball, L. A.: Induction, purification, and properties of 2′5′-oligoadenylate synthetase. Ann. N. Y. Acad. Sci. 350 (1980) 486–496

    Google Scholar 

  2. Billiau, A., P. De Somer, V. G. Edy, E. De Clercq, H. Heremans: Human fibroblast interferon for clinical trials: Pharmacokinetics and tolerability in experimental animals and humans. Antimicrob. Agents Chemother. 16 (1979) 56–63

    Google Scholar 

  3. Blalock, J. E., J. A. Georgiades, M. P. Langford, H. M. Johnson: Purified human immune interferon has more potent anticellular activity than fibroblast or leucocyte interferon. Cell. Immunol., 49 (1980) 390–394

    Google Scholar 

  4. Blomgren, H., K. Cantell, B. Johansson, C. Lagergren, U. Ringborg, H. Strander: Interferon therapy in Hodgkin's disease. Acta Med. Scand. 199 (1976) 527–532

    Google Scholar 

  5. Borden, E., T. Dao, J. Holland, J. Gutterman, T. Merigan: Interferon in recurrent breast carcinoma: preliminary report of the American Cancer Society clinical trials program. Proc. Am. Assoc. Cancer Res. Abstr., 750, 1980

  6. Boëtius, J., H. Blomgren, V. P. Collins, T. Greitz, H. Strander: The effect of systemic human interferonalpha administration to patients with glioblastoma multiforme. Acta Neurochir. 68 (1983) 239–251

    Google Scholar 

  7. Cathala, F., S. Baron: Interferon in rabbit brain, cerebrospinal fluid and serum following administration of polyinosinic-polycytidylic acid. J. Immunol. 104 (1970) 1355–1358

    Google Scholar 

  8. Cook, A. W., W. A. Carter, F. Nidzgorski, L. Akhtar: Human brain tumor-derived cell lines: Growth rate reduced by human fibroblast interferon. Science 18. Febr. (1983) 881–883

    Google Scholar 

  9. De Clercq, E., V. G. Edy, H. Vlieger, R. Eckels, J. Desmyter: Intrathecal administration of interferon in neonatal herpes. J. Pediatr. 86 (1975) 736–739

    Google Scholar 

  10. Donahoe, R. M., K. Huang: Interferon preparations enhance phagocytosis in vivo. Infect. Immun. 13 (1976) 1250–1257

    Google Scholar 

  11. Einhorn, S., H. Blomgren, H. Strander: Interferon and spontaneous cytotoxicity in man. II. Studies in patients receiving exogenous leucocyte interferon. Acta Med. Scand. 204 (1978) 477–483

    Google Scholar 

  12. Emödi, G., J. R. Hernandez, H. R. Hirt: Circulating interferon in man after administration of exogenous human leucocyte interferon. J. Natl. Cancer Inst. 54 (1975) 1045–1049

    Google Scholar 

  13. Feun, L., J. Gutterman, J. Quesada, D. Stewart, M. Leavens, M. A. Burgess, R. S. Benjamin: Phase I study of interferon administered via indwelling Ommaya reservoir for the treatment of progressive malignant gliomas. Abstr. of 13th Internatl. Cancer Congr. No. 963, Sheattle 1982

  14. Fleischmann, Jr., W. R., K. M. Kleyn, S. Baron: Potentiation of antitumour effect of virus-induced interferon by mouse immune interferon preparations. J. Natl. Cancer Inst. 65 (1980) 963–966

    Google Scholar 

  15. Gidlund, M., A. Oern, H. Wigzell, A. Senik, I. Gresser: Enhanced NK cell activity in mice injected with interferon and interferon inducers. Nature 273 (1978) 759–761

    Google Scholar 

  16. Gresser, I., C. Bourali, J. P. Levy, D. F. Brouty-Boye, M. T. Thomas: Increased survival in mice inoculated with tumour cells and treated with interferon preparations. Proc. Natl. Acad. Sci. 63 (1969) 51–57

    Google Scholar 

  17. Gresser, I.: Antitumour effects of interferon. Adv. Cancer Res. 16 (1972) 97–140

    Google Scholar 

  18. Gresser, I., M. G. Tovey: Antitumour effects of interferon. Biochem. Biophys. Acta 516 (1978) 231–247

    Google Scholar 

  19. Gutterman, J. U., G. R. Blumenschein, R. Alexanian, H. Y. Yap, A. U. Buzdar: Leucocyte interferoninduced tumour regression in human metastatic breast cancer, multiple myeloma, and malignant lymphoma. Ann. Intern. Med., 93 (1980) 399–406

    Google Scholar 

  20. Gutterman, J. U., S. Fine, J. Quesada, S. J. Horning, J. F. Levine, R. Alexanian, L. Bernhardt, M. Kramer, H. Spiegel, W. Colburn, P. Troen, T. Merigan, Z. Sziewanowski: Recombinant leucocyte A Interferon: Pharmacokinetics, single-dose tolerance, and biologic effects in cancer patients. Ann. Int. Med. 96 (1982) 549–556

    Google Scholar 

  21. Gutterman, J., J. Quesada: Clinical investigation of partially pure and recombinant DNA derived leucocyte interferon in human cancer. Texas Rep. Biol. Med. 41 (1982) 626–633

    Google Scholar 

  22. Habif, D. V., R. Lipton, K. Cantell: Interferon crosses blood-cerebrospinal fluid barrier in monkeys. Proc. Soc. Exp. Biol. Med. 149 (1975) 287–289

    Google Scholar 

  23. Hanley, D. F., M. Wiranowska-Stewart, W. E. Stewart II: Pharmacology of interferon I. Pharmacologic distinctions between human leucocyte and fibroblast interferons. Int. J. Immunopharmacol. 1 (1979) 219–226

    Google Scholar 

  24. Hill, N. O., E. Loeb, A. S. Pardue, G. L. Dorn, A. Khan, M. Hill: Response of acute leukemia to leucocyte interferon. J. Clin. Hematol. Oncol. 9 (1979) 137–149

    Google Scholar 

  25. Hill, N. O., A. Pardue, A. Khan, C. Aleman, R. Hilario, J. M. Hill: Clinical trials of human leucocyte interferon in malignancy. Texas Rep. Biol. Med. 41 (1982) 634–640

    Google Scholar 

  26. Hirakawa, K., S. Ueda, Y. Nakagawa, K. Suzuki, S. Fukuma, M. Kita, J. Imanishi, T. Kishida: Effect of human leucocyte interferon on malignant brain tumours. Cancer 51 (1983) 1976–1981

    Google Scholar 

  27. Ho, M., C. Nash, C. W. Morgan, J. A. Armstrong, R. G. Carroll, B. Postic: Interferon administered in the cerebrospinal space and its effect on rabies in rabbits. Infect. Immun. 9 (1974) 286–293

    Google Scholar 

  28. Horning, S. J., J. F. Levine, R. A. Miller, S. A. Rosenberg, T. C. Merigan: Clinical and immunologic effects of recombinant leucocyte A interferon in eight patients with advanced cancer. JAMA 247 (1982) 1718–1722

    Google Scholar 

  29. Horoszewitz, J. S., S. S. Leong, M. Ito, R. F. Buffett, C. Karakousis, E. Holyode: Human fibroblast interferon in human neoplasia: Clinical and laboratory study. Cancer Treat. Rep. 62 (1978) 1899–1906

    Google Scholar 

  30. Hovanessian, A. G., J. N. Wood: Anticellular and antiviral effects of pppA (2′5′A) n. Virol. 101 (1980) 81–90

    Google Scholar 

  31. Huddlestone, J. R., T. C. Merigan, M. B. A. Oldstone: Induction and kinetics of natural killer cell in humans following interferon therapy. Nature 282 (1979) 417–419

    Google Scholar 

  32. Ikic, D., J. Krusic, V. Kirhmajer, M. Knezevic, Z. Maricic: Application of human leucocyte interferon in patients with carcinoma of the uterine cervix. Lancet, May 9 (1981) 1027–1030

    Google Scholar 

  33. Isaacs, A., J. Lindenmann: Virus interference. I. The interferon. Proc. Royal Soc., B 147 (1957) 258–267

    Google Scholar 

  34. Isaacs, A., J. Lindenmann, R. C. Valentine: Virus interference. II. Some properties of interferon. Proc. Royal Soc., B 147 (1957) 268–273

    Google Scholar 

  35. Karnovsky, D. A.: Meaningful clinical classification of therapeutic responses to anticancer drugs. Clin. Pharmacol. Therapeut. 2 (1961) 709–712

    Google Scholar 

  36. Kimchi, A., H. Shure, M. Revel: Anti-mitogenic function of interferon-induced (2′-5′)Oligo(adenylate) and growth-related variations in enzymes that synthesize and degrade this oligonucleotide. Eur. J. Biochem. 114 (1981) 5–10

    Google Scholar 

  37. Kohase, M., S. Kohno, S. Yamazaki, A. Shishido, R. Kono: Potency standardization of human interferon preparations for clinical trials. In: Kono, R., J. Vilcek: The clinical potential of interferons Univ. of Tokyo Press, Tokyo (1982) 299–309

    Google Scholar 

  38. Korose, K., I. Takeshita, H. Mannoji, M. Fukui: Interferon effects on multiplication, cytoplasmic protein and GFAP content, and morphology in human glioma cells. J. Neurooncol. 1 (1983) 69–76

    Google Scholar 

  39. Larsson, I., L.-E. Landström, E. Larner, E. Lundgren, H. Miörner, O. Strannegard: Interferon production in glia and glioma cell lines. Infect. Immun. 22 (1978) 786–789

    Google Scholar 

  40. Lundblad, D., E. Lundgren: Block of a glioma cell line in S by interferon. Int. J. Cancer 27 (1981) 749–754

    Google Scholar 

  41. Mellstedt, H., A. Ahre, M. Bjorkholm, G. Holm, B. Johansson, H. Strander: Interferon therapy in myelomatosis. Lancet, Febr. 3 (1979) 245–247

    Google Scholar 

  42. Merigan, T. C.: Pharmacokinetics and side effects of interferon in man. Texas Rep. Biol. Med. 35 (1977) 541–547

    Google Scholar 

  43. Merigan, T. C., K. Sikora, J. H. Breeden, R. Levy, S. A. Rosenberg: Preliminary observations on the effect of human leukocyte interferon in non-Hodgkin's lymphoma. New Engl. J. Med. 299 (1978) 1449–1453

    Google Scholar 

  44. Merlin, G., M. Revel, D. Wallach: The interferoninduced enzyme oligo-isoadenylate synthetase: Rapid determination of its in vitro products. Analyt. Biochem. 110 (1981) 190–196

    Google Scholar 

  45. Mogensen, K. E., Ph. Daubas, I. Gresser, D. Sereni, B. Varet: Patient with circulating antibodies to α-interferon. Lancet, Nor. 28 (1981) 1227

    Google Scholar 

  46. Murphy, G. P.: Current report on the interferon program at Rosewell Park Memorial Institute. J. Surg. Oncol. 17 (1981) 99–111

    Google Scholar 

  47. Nagai, M., T. Arai, S. Kohno, M. Kohase: Interferon therapy for malignant brain tumours. In: Kono. R., J. Vilcek: The clinical potential of interferons, 257–273. Univ. of Tokyo Press, Tokyo 1982

    Google Scholar 

  48. Nagai, M., T. Arai: Interferon as a treatment for malignant brain tumours. Abstr. of 7th Internatl. Congr. of Neurol. Surg. No. 8.8.10. Munich 1981

  49. Nagai, M., T. Arai: Interferon therapy for malignant brain tumors — Present and future —. Neurol. Surg. 10 (1982) 463–476

    Google Scholar 

  50. Nagai, M., T. Arai, S. Kohno, M. Kohase: Local application of interferon to malignant brain tumours. Texas Rep. Biol. Med. 41 (1982) 693–698

    Google Scholar 

  51. Nagai, M., T. Arai, S. Kohno, E. Iizuka: Present state of interferon therapy on malignant brain tumours. Jap. J. Cancer Clin. 29 (1983) 608–615

    Google Scholar 

  52. Niethammer, D., J. Treuner: Pharmacological and therapeutical experience with human interferon-β in malignant tumours in children. Texas Rep. Biol. Med. 41 (1982) 641–645

    Google Scholar 

  53. Nuwer, M. R., E. De Clercq, T. C. Merigan: Interferon clearance rate decreased after repeated injections. J. Gen. Virol. 12 (1971) 191–194

    Google Scholar 

  54. Ommaya, A. K., M. A. Okon, M. B. Punjab: Subcutaneous reservoir and pump for sterile access to ventricular cerebrospinal fluid. Lancet, 2 (1963) 983–984

    Google Scholar 

  55. Pape, G. R., M. R. Hadam, J. Eisenburg, G. Riethmüller: Kinetics of natural cytotoxicity in patients treated with human fibroblast interferon. Cancer Immunol. Immunother. 11 (1981) 1–6

    Google Scholar 

  56. Paucker, K., K. Cantell, W. Henle: Quantitative studies on viral interference in suspended L cells. III. Effect of interfering viruses and interferon on the growth rate of cells. Virol. 17 (1962) 327–334

    Google Scholar 

  57. Priestman, T. J.: Initial evaluation of human lymphoblastoid interferon in patients with advanced malignant desease. Lancet. July 19 (1980) 113–118

    Google Scholar 

  58. Rubin, B. Y., S. L. Gupta: Differential efficacies of human type I and type II interferons as antiviral and antiproliferative agents. Proc. Natl. Acad. Sci. 77 (1980) 5928–5932

    Google Scholar 

  59. Salford, L. G., S. Borgström, J. Brismar, A. Brun, S. Cronqvist: Intratumoral and systemic interferon treatment of astrocytomas grade III-IV. Abstr. of U.S.-Japanese Confer. on Brain Tumor Therapy. Nikko, Japan, (1981)

  60. Senik, A., I. Gresser, C. Naury, M. Gidlund, A. Orn, H. Wigzell: Enhancement by interferon of natural killer cell activity in mice. Cell. Immunol. 44 (1979) 186–200

    Google Scholar 

  61. Schultz, R. M.: Factors limiting tumouricidal function of interferon-induced effector systems — Activated macrophages and natural killer cells. Cancer Immunol. Immunother. 10 (1981) 61–66

    Google Scholar 

  62. Sherwin, S. A., J. A. Knost, S. Fein, P. G. Abrams, K. A. Foon, J. J. Ochs, C. Schoenberger, A. E. Maluish, R. K. Oldham: A multiple-dose phase I trial of recombinant leucocyte A interferon in cancer patients. JAMA 248 (1982) 2461–2466

    Google Scholar 

  63. Strander, H., K. Cantell, G. Carlström, P. A. Jakobsson: Clinical and laboratory investigations on man: Systemic administration of potent interferon to man. J. Natl. Cancer Inst. 51 (1973) 733–742

    Google Scholar 

  64. Strander, H., K. Cantell, P. A. Jakobsson, U. Nilsonne, G. Söderberg: Exogenous interferon therapy of osteogenic sarcoma. Acta Orthop. Scand. 45 (1974) 958–959

    Google Scholar 

  65. Strander, H., S. Einhorn: Effect of human leucocyte interferon on the growth of human osteosarcoma cells in tissue culture. Int. J. Cancer 19 (1977) 468–473

    Google Scholar 

  66. Strander, H.: Interferon therapy of malignant disease. In: Kono, R., J. Vilcek: The clinical potential of interferons (1982) 179–185, Univ. of Tokyo Press, Tokyo

    Google Scholar 

  67. Trinchieri, G., D. Santoli: Anti-viral activity induced by culturing lymphocytes with tumour-derived or virus-transformed cells. Enhancement of human natural killer cell activity by interferon and antagonistic inhibition of susceptibility of target cells to lysis. J. Exp. Med. 147 (1978) 1314–1320

    Google Scholar 

  68. Trinchieri, G., D. Santoli, H. Koprowski: Spontaneous cellmediated cytotoxicity in humans: Role of interferon and immunoglubulins. J. Immunol. 120 (1978) 1849–1855

    Google Scholar 

  69. Vallbracht, A., J. Treuner, B. Flemig, K.-E. Joester, D. Niethammer: Interferon-neutralizing antibodies in a patient treated with human fibroblast interferon. Nature 289 (1981) 496–497

    Google Scholar 

  70. Wood, J. N., A. G. Hovanessian: Interferon enhances 2-5A synthetase in embryonal carcinoma cells. Nature 282 (1979) 74–79

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nagai, M., Arai, T. Clinical effect of interferon in malignant brain tumours. Neurosurg. Rev. 7, 55–64 (1984). https://doi.org/10.1007/BF01743290

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01743290

Keywords

Navigation