Abstract
A logical inference from the recent reports indicating that malignant brain tumors are composed of a heterogeneous cell population is that combination chemotherapy will be required for effective brain tumor control. For several years we have been investigating the use of Bleomycin as an agent to be used in conjunction with radiation therapy and a nitrosourea compound. Since systemically administered Bleomycin does not cross the blood-brain-barrier and has significant toxicity when used parenterally in high doses, we have studied the use of smaller doses of Bleomycin injected directly into the brain tumor cavity. Such an intracerebral dose was more effective in prolonging survival of rats burdened with experimental 9L gliosarcomas than an intravenous dose that is 25 times as great. The combination of intracerebrally administered Bleomycin and radiation therapy was more effective than either modality alone. Furthermore, the combination of Bleomycin delivered intracerebrally and BCNU given systemically was more effective than eitheragent used alone.
Finally, in a Phase I clinical trial of Bleomycin given via an Ommaya reservoir to eight patients with recurrent malignant brain tumors, we have demonstrated that individual doses of up to 7.5 units and cumulative doses of up to 255 units can be administered without significant toxicity.
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References
Walker MD, Greed SB, Byar DP: Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Engl J Med 303: 1323–1329, 1980.
Bigner PD, Bigner SH, Ponten J, Westermark B, Mahaley MS: Heterogeneity of genotypic and phenotypic characteristics of fifteen permanent cell lines derived from human gliomas. J Neuropathol Exp Neurol 15: 201–229, 1981.
Shapiro JR, Yung WA, Shapiro WR: Isolation, karyotype and clonal growth of heterogeneous subpopulations of human malignant gliomas. Cancer Res 41: 2349–2359, 1981.
Hoshino T, Knebel KD, Rosenblum ML, Dougherty DV, Wilson CB: Clonogenicity of multiple populations of human glioma cells in vitro sorted by DNA content. Cancer 50: 997–1002, 1982.
Henderson SD, Kimler BF, Morantz RA: Radiation therapy of 9L rat brain tumors. Int J Radiat Oncol Biol Phys 7: 497–502, 1981.
Zar JH: Biostatistical analysis. Prentice-Hall, Inc, Englewood Cliffs, NJ, 1974, pp 198–235.
Gehan EA: A generalized Wilcoxon test for comparing arbitrarily singly-censored samples. Biometrika 52: 203–223, 1965.
Vats TS, Morantz RA, Wood GW, Tilzer S: Study of effectiveness of Bleomycin in rat brain tumor model intravenously and intracerebrally. Int J Radiat Oncol Biol Phys 5: 1527–1529, 1979.
Kimler BF, Vats TS, Morantz RA, Henderson SD: Response of the 9L rat brain tumor to combination treatment with radiation and Bleomycin. Int J Radiat Oncol Biol Phys 7: 1069–1074, 1981.
Henderson SD, Kimler BF: Interaction of Bleomycin and radiation on the survival of synchronous 9L cells. Cancer Res (submitted).
Vats TS, Kimler BF, Henderson SD, Morantz RA: Combination chemotherapy for the 9L rat brain tumor model system. Cancer Treat Rep 66: 575–579, 1982.
Levin VA, Edwards MS, Byrd A: Quantitative observations of the acute effects of x-irradiation on brain capillary permeability: part 1. Int J Radiat Oncol Biol Phys 5: 1627–1631, 1979.
Hayakawa T, Ushro Y, Mogami H: The uptake, distribution and antitumor activity of Bleomycin in gliomas in the mouse. Eur J Cancer 10: 137–142, 1974.
Hayakawa T, Ushro Y, Morimoto K: Uptake of Bleomycin by human brain tumors. J Neurol Neurosurg Psychiatry 39: 341–349, 1976.
Takeuchi K: A clinical trial of intravenous Bleomycin in the treatment of brain tumors. Int J Clin Pharmacol 12: 419–426, 1975.
Kristiansen K., Hagen S, Kollevold T et al: Combined modality therapy of operated astrocytomas grade III and IV. Confirmation of the value of post-operative irradiation and lack of potentiation of Bleomycin on survival time. Cancer 47: 649–652, 1981.
Bosch DA, Hindmorsch TH, Larsson ST, Backlund EO: Intraneoplastic administration of Bleomycin in intracerebral gliomas, a pilot study. Acta Neurochir [Suppl] 30: 441–444, 1980.
Hochberg FH, Pruit, A: Assumptions in the radiotherapy of glioblastomas. Neurology 30: 907–911, 1980.
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Address for reprints: Dr. Bruce F. Kimler, Department of Radiation Therapy, University of Kansas Medical Center, Rainbow Boulevard at 39th Street, Kansas City, KS 66103, USA
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Morantz, R.A., Kimler, B.F., Vats, T.S. et al. Bleomycin and brain tumors. J Neuro-Oncol 1, 249–255 (1983). https://doi.org/10.1007/BF00165609
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DOI: https://doi.org/10.1007/BF00165609