Abstract
Eleven patients with malignant gliomas recurring after surgery and radiation therapy, were treated with high dose BCNU 1050-1200 mg/ M2 with autologous bone marrow rescue. Four patients also received concomitant 5-fluorouracil 1000 mg/ M2/24 hr daily for three days. Eight of ten evaluable patients demonstrated improvement on CAT scan as well as a decrease in steroid requirement. All patients surviving longer than two weeks after BCNU administration experienced full hematologic recovery. No delayed myelosuppression was seen after a single course of high dose therapy. Two patients died as a result of therapy, one following a second induction of BCNU for a total cumulative BCNU dose of 2 400 mg/ M2 and one of infection while cytopenic. Additional toxicity includes one steroid-responsive interstitial pneumonitis, one centrilobular necrosis of the liver which spontaneously resolved and one episode of deep vein thrombosis. With limitation on the maximum BCNU dose and distribution of the total dose over three days, high dose BCNU can be administered with acceptable toxicity. This approach may offer a higher response rate than that expected for standard dose BCNU.
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References
Cancer statistics, 1982. CA 32:1–32, 1982.
Tonnis W, Walter N: Das glioblastome multiforme (Bericht über 2611 Fälle). Acta Neurochir (Wein) 6:40–46, 1959.
Walker MD, Strike TA, Sheline GE: An analysis of dose-response response relationship in the radiotherapy of malignant gliomas. Int J Radiat Oncol Biol Phys 5:1725–1731, 1979.
Wilson CB, Boldrey EB, Knot KJ: 1,3-bis(2-chloroethyl)-l-nitrosoureas (NSC-409962) in the treatment of brain tumors. Cancer Chemother Rep 54:273–281, 1970.
Wilson CB, Levin VA, Sheline GE: Management of CNS tumors in adult patients. In: Carter SK, Glatstein E, Livingston RB (eds) Principles of cancer treatment. McGraw-Hill, New York, 1982, pp 832–840.
Rosenblum ML, Dien DF, Hoshino T, Dougherty DA, Williams ME, Wilson CB: Comparison of clonogenic cell assays after in vivo and in vitro treatment of 9L gliosarcoma. Br J Cancer 41:307–308, 1980.
Takvorian T, Hochberg F, Canellos G, Parker L, Zervas N, Frei E: The toxicity of high-dose BCNU with autologous marrow support. In: Prestayko AW, Crooke ST, Baker LH, Carter SK, Schein PS (eds) Nitrosoureas. Current status and new developments. Academic Press, New York, 1981, pp 155–168.
Appelbaum FR, Herzig GP, Ziegler JL, Graw RG, Levine AS, Deisseroth AB: Successful engraftment of cryopreserved autologous bone marrow in patients with malignant lymphoma. Blood 52:85–95, 1979.
Patten GA, Billi JE, Rotman HH: Rapidly progressive, fatal pulmonary fibrosis induced by Carmustine. JAMA 244: 687–688,1980.
Durant JR, Norgard MJ, Murad TM, Bartolucci AA, Langford KH: Pulmonary toxicity associated with bischloroethylnitrosourea (BCNU). Ann Intern Med 90:191–194, 1979.
Holoye PY, Jenkins DE, Greenberg SD: Pulmonary toxicity in long-term administration of BCNU. Cancer Treat Rep 60:1691–1694,1976.
Aronin PA, Mahaley MS, Rudnick SA, Dudka L, Donohue JF, Selker RG, Moore P: Prediction of BCNU pulmonary toxicity in patients with malignant gliomas. N Engl J Med 303:183–188,1980.
Hochberg FH, Parker LM, Takvorian T, Canellos GP, Zervas NT: High dose BCNU with autologous bone marrow rescue for recurrent glioblastoma multiforme. J Neurosurg 54:455–460,1981.
Burger PC, Kamenar E, Schold SC, Fay JW, Phillips GL, Herzig GP: Encephalomyelopathy following high-dose BCNU therapy. Cancer 48:1318–1327, 1981.
Phillips GL, Fay JW, Herzig GP, Weiner RS, Wolff SN, Lazarus H, Karanes C, Ross W, Kramer B: Phase I–II study: intensive BCNU (1,3-Bis[2-chloroethyl]-1-nitrosourea, NSC #409962) and autologous bone marrow transplantation for refractory cancer. Cancer (in press).
Herzig GP, Phillips GL, Herzig RH, Fay JW, Weiner RL, Wolff SN, Lazarus HM: High-dose nitrosourea (BCNU) and autologous bone marrow transplantation: a phase I study. In: Prestayko AW, Cooke ST, Baker LH, Carter SK, Schein PS (eds) Nitrosoureas. Current status and new developments. Academic Press, New York, 1981, pp 337–341.
Lokich JJ, Drum DE, Kaplan W: Hepatic toxicity of nitrosourea analogues Clin Pharmacol Ther 16:363–367, 1974.
Levin VA, Hoffman WF, Pischer TL, Seager ML, Boldrey EB, Wilson CB: BCNU-5-fluorouracil combination therapy for recurrent malignant brain tumors. Cancer Treat Rep 62:2071–2076, 1978.
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Address for reprints: Joanne E. Mortimer, M.D., University of Washington, NN111 University Hospital, RC-O8, 1959 N.E. Pacific Street, Seattle, WA 98195, USA
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Mortimer, J.E., Hewlett, J.S., Bay, J. et al. High dose BCNU with autologous bone marrow rescue in the treatment of recurrent malignant gliomas. J Neuro-Oncol 1, 269–273 (1983). https://doi.org/10.1007/BF00165611
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DOI: https://doi.org/10.1007/BF00165611