Phase II evaluation of dibromodulcitol in the treatment of recurrent medulloblastoma, ependymoma, and malignant astrocytoma

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✓ The authors have conducted a Phase II trial to evaluate orally administered dibromodulcitol in the treatment of 40 evaluable patients with recurrent medulloblastoma, ependymoma, and malignant astrocytoma. Ten of 20 patients harboring medulloblastoma responded to therapy with a median time to tumor progression (MTP) of 40 weeks, and four of 20 patients had no sign of progression of disease 4 years after treatment was begun. The MTP for all 12 patients with ependymoma was 30 weeks. Nine of these 12 patients had stabilization of their disease with an MTP of 67 weeks; three of these 12 patients had no signs of progression for 1 to 3 years after treatment was begun. Of six patients harboring supratentorial gliomas, none responded to dibromodulcitol. Two patients, one with a primitive neuroectodermal tumor and the other with a metastatic carcinoma of the breast, had stabilization of disease for more than 4 and 2 years, respectively.

Article Information

Present address for Dr. Fulton: Neurology Unit, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.

Address reprint requests to: Victor A. Levin, M.D., Brain Tumor Research Center, 783 HSW, University of California, San Francisco, California 94143.

© AANS, except where prohibited by US copyright law.

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Figures

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    Kaplan-Meier representation of the probability of freedom from tumor progression for all 20 medulloblastoma patients (solid line) and the subset of 10 patients who responded or stabilized after treatment with dibromoducitol (broken line). The ticks represent patients censored from evaluation because they have not yet failed therapy.

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    Kaplan-Meier representation of the probability of freedom from tumor progression for all 12 ependymoma patients. The ticks represent patients censored from evaluation because they have not yet failed therapy.

References

  • 1.

    Afra DKocsis BDobay Iet al: Combined radiotherapy and chemotherapy with dibromodulcitol and CCNU in the postoperative treatment of malignant gliomas. J Neurosurg 59:1061101983Afra D Kocsis B Dobay I et al: Combined radiotherapy and chemotherapy with dibromodulcitol and CCNU in the postoperative treatment of malignant gliomas. J Neurosurg 59:106–110 1983

  • 2.

    Allen JCHelson L: High-dose cyclophosphamide chemotherapy for recurrent CNS tumors in children. J Neurosurg 55:7497561981Allen JC Helson L: High-dose cyclophosphamide chemotherapy for recurrent CNS tumors in children. J Neurosurg 55:749–756 1981

  • 3.

    Andrews NCWeiss AJAnfield FJet al: Phase I study of dibromodulcitol (NSC-104800). Cancer Chemother Rep 55:61651971Andrews NC Weiss AJ Anfield FJ et al: Phase I study of dibromodulcitol (NSC-104800). Cancer Chemother Rep 55:61–65 1971

  • 4.

    Andrews NCWeiss AJWilson Wet al: Phase II study of dibromodulcitol (NSC-104800). Cancer Chemother Rep 58:6536601974Andrews NC Weiss AJ Wilson W et al: Phase II study of dibromodulcitol (NSC-104800). Cancer Chemother Rep 58:653–660 1974

  • 5.

    Belej MATroetel WMWeiss AJet al: The absorption and metabolism of dibromodulcitol in patients with advanced cancer. Clin Pharmacol Ther 13:5635721972Belej MA Troetel WM Weiss AJ et al: The absorption and metabolism of dibromodulcitol in patients with advanced cancer. Clin Pharmacol Ther 13:563–572 1972

  • 6.

    Bellet RECatalano RBMastrangelo MJet al: Positive phase II trial of dibromodulcitol in patients with metastatic melanoma refractory to DTIC and a nitrosourea. Cancer Treat Rep 62:209520991978Bellet RE Catalano RB Mastrangelo MJ et al: Positive phase II trial of dibromodulcitol in patients with metastatic melanoma refractory to DTIC and a nitrosourea. Cancer Treat Rep 62:2095–2099 1978

  • 7.

    Berry MPJenkin RDTKeen CWet al: Radiation treatment for medulloblastoma. A 21-year review. J Neurosurg 55:43511981Berry MP Jenkin RDT Keen CW et al: Radiation treatment for medulloblastoma. A 21-year review. J Neurosurg 55:43–51 1981

  • 8.

    Cangir Avan Eys JBerry DHet al: Combination chemotherapy with MOPP in children with recurrent brain tumors. Med Pediatr Oncol 4:2532611978Cangir A van Eys J Berry DH et al: Combination chemotherapy with MOPP in children with recurrent brain tumors. Med Pediatr Oncol 4:253–261 1978

  • 9.

    Chiuten DFRozencweig MVon Hoff DDet al: Clinical trials with the hexitol derivatives in the U.S. Cancer 47:4424511981Chiuten DF Rozencweig M Von Hoff DD et al: Clinical trials with the hexitol derivatives in the U.S. Cancer 47:442–451 1981

  • 10.

    Crafts DCLevin VAEdwards MSBet al: Chemotherapy of recurrent medulloblastoma with combined procarbazine, CCNU, and vincristine. J Neurosurg 49:5895921978Crafts DC Levin VA Edwards MSB et al: Chemotherapy of recurrent medulloblastoma with combined procarbazine CCNU and vincristine. J Neurosurg 49:589–592 1978

  • 11.

    Duffner PKCohen METhomas PRMet al: Combination chemotherapy in recurrent medulloblastoma. Cancer 43:41451979Duffner PK Cohen ME Thomas PRM et al: Combination chemotherapy in recurrent medulloblastoma. Cancer 43:41–45 1979

  • 12.

    Eckhardt S: Ten-year international clinical experience with DBD in the treatment of malignant diseases in Eckhardt S (ed): Dibromodulcitol. Budapest: Medicina Konyvkiado1982 pp 174188Eckhardt S: Ten-year international clinical experience with DBD in the treatment of malignant diseases in Eckhardt S (ed): Dibromodulcitol. Budapest: Medicina Konyvkiado 1982 pp 174–188

  • 13.

    Edwards MSLevin VAWilson CB: Brain tumor chemotherapy: an evaluation of agents in current use for phase II and III trials. Cancer Treat Rep 64:117912051980Edwards MS Levin VA Wilson CB: Brain tumor chemotherapy: an evaluation of agents in current use for phase II and III trials. Cancer Treat Rep 64:1179–1205 1980

  • 14.

    Horváth IPCsetényi JKerpel-Fronius Set al: Metabolism and pharmacokinetics of dibromodulcitol (DBD, NSC-104800) in man. I. Metabolites of DBD. Eur J Cancer Clin Oncol 15:3373441979Horváth IP Csetényi J Kerpel-Fronius S et al: Metabolism and pharmacokinetics of dibromodulcitol (DBD NSC-104800) in man. I. Metabolites of DBD. Eur J Cancer Clin Oncol 15:337–344 1979

  • 15.

    Kaplan ELMeier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:4574811958Kaplan EL Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481 1958

  • 16.

    Kumar ARVRenaudin JWilson CBet al: Procarbazine hydrochloride in the treatment of brain tumors. Phase 2 study. J Neurosurg 40:3653711974Kumar ARV Renaudin J Wilson CB et al: Procarbazine hydrochloride in the treatment of brain tumors. Phase 2 study. J Neurosurg 40:365–371 1974

  • 17.

    Levin VA: Chemotherapy of recurrent brain tumors in Prestayko AWCrooke ST (eds): Nitrosoureas: Current Status and New Developments. New York: Academic Press1981 pp 159167Levin VA: Chemotherapy of recurrent brain tumors in Prestayko AW Crooke ST (eds): Nitrosoureas: Current Status and New Developments. New York: Academic Press 1981 pp 159–167

  • 18.

    Levin VA: Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability. J Med Chem 23:6826841980Levin VA: Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability. J Med Chem 23:682–684 1980

  • 19.

    Levin VACrafts DCNorman DMet al: Criteria for evaluating patients undergoing chemotherapy for malignant brain tumors. J Neurosurg 47:3293351977Levin VA Crafts DC Norman DM et al: Criteria for evaluating patients undergoing chemotherapy for malignant brain tumors. J Neurosurg 47:329–335 1977

  • 20.

    Levin VAVestnys PSEdwards MSBet al: Improvement in survival produced by sequential therapies in the treatment of recurrent medulloblastoma. Cancer 51:136413701983Levin VA Vestnys PS Edwards MSB et al: Improvement in survival produced by sequential therapies in the treatment of recurrent medulloblastoma. Cancer 51:1364–1370 1983

  • 21.

    Levin VAWheeler KT: Chemotherapeutic approaches to brain tumors. Experimental observations with dianhydrogalactitol and dibromodulcitol. Cancer Chemother Pharmacol 8:1251311982Levin VA Wheeler KT: Chemotherapeutic approaches to brain tumors. Experimental observations with dianhydrogalactitol and dibromodulcitol. Cancer Chemother Pharmacol 8:125–131 1982

  • 22.

    Nomura KHoshino TDeen DFet al: Perturbed cell kinetics of 9L rat brain tumor cells following dianhydrogalactitol. Cancer Treat Rep 62:205520611978Nomura K Hoshino T Deen DF et al: Perturbed cell kinetics of 9L rat brain tumor cells following dianhydrogalactitol. Cancer Treat Rep 62:2055–2061 1978

  • 23.

    Sellei CEckhardt SHorváth IPet al: Clinical and pharmacologic experience with dibromodulcitol (NSC-104800), a new antitumor agent. Cancer Chemother Rep 53:3773841969Sellei C Eckhardt S Horváth IP et al: Clinical and pharmacologic experience with dibromodulcitol (NSC-104800) a new antitumor agent. Cancer Chemother Rep 53:377–384 1969

  • 24.

    Sitarz ALAlbo VMovassaghi Net al: Dibromodulcitol (NSC-104800) compared with cyclophosphamide (NSC-26271) as remission maintenance therapy in previously treated children with acute lymphoblastic leukemic or acute undifferentiated leukemia: possible effectiveness in reducing the incidence of central nervous system leukemia. Cancer Chemother Rep 59:9899941975Sitarz AL Albo V Movassaghi N et al: Dibromodulcitol (NSC-104800) compared with cyclophosphamide (NSC-26271) as remission maintenance therapy in previously treated children with acute lymphoblastic leukemic or acute undifferentiated leukemia: possible effectiveness in reducing the incidence of central nervous system leukemia. Cancer Chemother Rep 59:989–994 1975

  • 25.

    Wilson CBGutin PBoldrey EBet al: Single-agent chemotherapy of brain tumors. A five-year review. Arch Neurol 33:7397441976Wilson CB Gutin P Boldrey EB et al: Single-agent chemotherapy of brain tumors. A five-year review. Arch Neurol 33:739–744 1976

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