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Pathophysiologic Basis for Brain Tumor Chemotherapy

  • Chapter
Management of Childhood Brain Tumors

Part of the book series: Foundations of Neurological Surgery ((FONS,volume 3))

Abstract

In order to understand the rationale underlying brain tumor chemotherapy, it is important to review the unique properties of brain tumors. Unlike most carcinomas and sarcomas that are malignant because of their propensity to metastasize, brain tumors generally remain confined to the central nevous system. Histologically, they span a spectrum from slow-growing, low-grade astrocytomas to the aggressive glioblastoma multiforme, a tumor with the capacity to double in size every six days [1]. Unfortunately, brain tumors may be of very small size and low histologic grade, such as a brainstem astrocytoma, but can nevertheless rapidly kill the patient if untreated. In systemic tumors, it is generally felt that one kilogram (1012 cells) of tumor burden is lethal to the patient. In the setting of a brain tumor, 100 grams or less can be lethal.

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References

  1. Trott KR, Kummermehr J: What is known about tumor proliferation rates to choose between accelerated fractionation and hyper-fractionation? Radiother Oncol 3 (1):1–9, 1985.

    PubMed  CAS  Google Scholar 

  2. Shapiro WR: Combined modality treatment of malignant glioma. Prog Exp Tumor Res 29:219–224, 1985.

    PubMed  CAS  Google Scholar 

  3. Ransohoff J: The role of intracranial surgery for the treatment of malignant gliomas. In Walker MD (ed), Oncology of the Nervous System. Dordrecht: Martinus-Nijhoff, 1983.

    Google Scholar 

  4. Klatzo I: Neuropathological aspects of brain edema. J Neuropath Exp Neurol 26:1–14, 1967.

    PubMed  CAS  Google Scholar 

  5. Fishman RA: Brain edema. N Engl J Med 293:706–711, 1975.

    PubMed  CAS  Google Scholar 

  6. Waggener JD, Beggs JL: Vascularity of neural neoplasms. Adv Neurol 15:27–49, 1976.

    PubMed  CAS  Google Scholar 

  7. Reulen HJ, Tsuyumu M, Tack A., et al.: Clearance of edema fluid into the cerebral spinal fluid, a mechanism for resolution of vasogenic brain edema. J Neurosurg 48: 754–764, 1978.

    PubMed  CAS  Google Scholar 

  8. Reulen HJ: Vasogenic brain edema: New aspects on its formulation, resolution, and therapy. Br J Anesth 48:754–764, 1978.

    CAS  Google Scholar 

  9. Levin LA, Freeman-Dove M, Landahl HD: Permeability characteristics of brain Adjacent to tumors in rats. Arch Neurol 32:785–791, 1975.

    PubMed  CAS  Google Scholar 

  10. Brooks DJ, Beaney RP, Lammertsma AA, et al.: Quantitative measurement of blood brain barrier permeability using 82Rb and positron emission tomography. J Cereb Blood Flow Metabol 4:535–545, 1984.

    CAS  Google Scholar 

  11. Yen CK, Yano Y, Budinger J, et al.: Brain tumor evaluation using Rb-82 and positron emission tomography. J Nucl Med 23:532–537, 1982.

    PubMed  CAS  Google Scholar 

  12. Long DM, Hartmann JF, French LA: The response of cerebral edema to glucocorticoid administration: An electron microscopic study. Neurology 16:521–528, 1966.

    PubMed  CAS  Google Scholar 

  13. Shapiro WR, Posner JB: Corticosteroid hormones: Effects in an experimental brain tumor. Arch Neurol 30:217–221, 1974.

    PubMed  CAS  Google Scholar 

  14. Bracken MB, Collins WF, Freeman DF, et al.: Efficacy of methylprednisolone in acute spinal injury. JAMA 251:45–52, 1984.

    PubMed  CAS  Google Scholar 

  15. Bracken MB, Shepard MJ, Hellenbrand KG, Collins WF, Leo LS, et al.: Methylprednisolone and neurological function 1 year after spinal cord injury. J Neurosurg 63:704–713, 1985.

    PubMed  CAS  Google Scholar 

  16. Balis FM, Lester CM, Chrousos GP, Heideman RL, Poplack DG: Differences in cerebrospinal fluid penetration of corticosteroids: Possible relationship to the prevention of meningeal leukemia. J Clin Oncol 5:202–207, 1987.

    PubMed  CAS  Google Scholar 

  17. Gutin PH: Corticosteroid therapy in patients with cerebral tumors: Benefits, mechanisms, problems, practicalities. Semin Oncol 2(1):49–56, 1975.

    PubMed  CAS  Google Scholar 

  18. Weiss MH, Nulsen FE: The effect of glucocorticoids on cerebral spinal fluid flow in dogs. J Neurosurg 32:452–458, 1970.

    PubMed  CAS  Google Scholar 

  19. Weinstein JD, Toy FJ, Jaffe ME, Goldberg HI: The effect of dexamethasone on brain edema in patients with metastatic brain tumors. Neurology 23:121–129, 1972.

    Google Scholar 

  20. Miller JD, Sakalas R, Ward JD, Young HF, Adams WE, Vries JK, Becker DP: Methylprednisolone treatment in patients with brain tumors. Neurosurgery 1(2): 114–117, 1977.

    PubMed  CAS  Google Scholar 

  21. Schurmann K, Reulen HJ, Hadjidimos A: The influence of dexamethasone and diuretics on perifocal cerebral edema in brain tumors. J Neurosurg Sci 17:68, 1973.

    Google Scholar 

  22. Meinig G, Aulich A, Wende S, Ruelen HJ: The effect of dexamethasone and diuretic on peritumor brain edema: A comparative study of tissue water content and CT. In Pappius HM, Feindel W (eds), Dynamics of Brain Edema. New York: Springer-Verlag, 1976, pp 301–305.

    Google Scholar 

  23. Javid M: Urea in intracranial surgery. A new method. J Neurosurg 18:51–57, 1961.

    PubMed  CAS  Google Scholar 

  24. Wise BL, Chater N: The value of hypertonic mannitol solution in decreasing brain mass and lowering cerebral spinal fluid pressure. J Neurosurg 19:1038–1043, 1962.

    PubMed  CAS  Google Scholar 

  25. James HE, Langfitt TW, Kumar VSX: Treatment of intracranial hypertension: Analysis of 105 consecutive continuous recordings of intracranial pressure. Acta Neurochir 36: 189–200, 1977.

    CAS  Google Scholar 

  26. Mealey J, Chen TT, Schanz GP: The effects of dexamethasone and methylprednisone on cell cultures of human glioblastoma. J Neurosurg 34:324–334, 1971.

    PubMed  CAS  Google Scholar 

  27. Sherbert GV, Lakshmi MS, Haddah SK: Does dexamethasone inhibit the growth of human gliomas? J Neurosurg 47:864–870, 1977.

    CAS  Google Scholar 

  28. Zager RF, Frisby SA, Oliverio VT: Cellular transport and antitumor action of methotrexate with several drugs. Proc AACR 13:33, 1972.

    Google Scholar 

  29. Rapoport SI: Blood Brain Barrier in Physiology and Medicine. New York: Raven Press, 1976.

    Google Scholar 

  30. Rail DP, Zubrod CG: Mechanisms of drug absorption and excretion: passage of drugs in and out of the CNS. Ann Rev Pharmacol 2:109–128, 1962.

    Google Scholar 

  31. Edwards 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.

    PubMed  CAS  Google Scholar 

  32. Brightman MW, Reese TS, Vick NA, et al: A mechanism underlying the lack of a blood brain barrier to peroxidase in virally induced brain tumors. J Neuropath Exp Neurol 30: 139, 1971.

    PubMed  CAS  Google Scholar 

  33. Ausman JI, Levin VA, Brown WE, et al.: Brain tumor chemotherapy: Pharmacologic principles derived from a monkey brain tumor model. J Neurosurg 46:155–164, 1977.

    PubMed  CAS  Google Scholar 

  34. Levin VA, Chadwick M: Distribution of 5-FU-2-14C and its metabolites in a murine glioma. J Natl Cancer Inst 49:1577–1584, 1972.

    PubMed  CAS  Google Scholar 

  35. Tator CH: Retention of tritiated methotrexate in transplantable mouse glioma. Cancer Res 36:3058–3066, 1976.

    PubMed  CAS  Google Scholar 

  36. Levin VA, Clancy TP, Ausman JI, Rail DP: Uptake and distribution of 3H-methotrexate by murine ependymoblastoma. J Natl Cancer Inst 48:875–883, 1972.

    PubMed  CAS  Google Scholar 

  37. Brooks DJ, Beaney RP, Thomas DGT: The role of positron emission tomography in the study of cerebral tumors. Semin Oncol 13(1): 83–93, 1986.

    PubMed  CAS  Google Scholar 

  38. Long DM: Capillary ultrastructure and the blood brain barrier in human malignant brain tumors. J Neurosurg 32:127–144, 1970.

    PubMed  CAS  Google Scholar 

  39. Hirano A, Matsui T: Vascular structures in brain tumors. Hum Path 6:611–621, 1975.

    PubMed  CAS  Google Scholar 

  40. Waggener JD, Beggs JL: Vasculature of neural neoplasms. Adv Neurol 15:27–49, 1976.

    PubMed  CAS  Google Scholar 

  41. Shapiro WR, Ausman JI, Rall DP: Studies on the chemotheraphy of experimental brain tumors: Evaluation of 1, 3-bis (2-chloroethyl)-1-nitrosourea, cyclophosphamide, mithramycin and methotrexate. Cancer Res 30: 2401–2413, 1970.

    PubMed  CAS  Google Scholar 

  42. Shapiro WR: Studies on the chemotherapy of experimental brain tumors: Evaluation of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, vincristine, and 5-FU. J Natl Cancer Inst 46:359–368, 1971.

    PubMed  CAS  Google Scholar 

  43. Shapiro WR: The effect of chemotherapeutic agents on the incorporation of DNA precursors by experimental brain tumors. Cancer Res 32:2178–2185, 1972.

    PubMed  CAS  Google Scholar 

  44. Levin VA, Wilson CB: Correlations between experimental chemotherapy in the murine glioma and effectiveness of clinical therapy regimens. Cancer Chemother Pharmacol 1: 41–48, 1978.

    PubMed  CAS  Google Scholar 

  45. Hawkins RA, Phelps ME, Huang SC, et al.: A kinetic evaluation of blood brain barrier permeability in human brain tumors with 68GA-EDTA and positron emission tomography. J Cereb Blood Flow Metab 4:507–515, 1984.

    PubMed  CAS  Google Scholar 

  46. Levin VA, Landahl HD, Freeman-Dove MA: The application of brain capillary permeability coefficient measurements to pathological conditions and the selection of agents which cross the blood brain barrier. J Pharmacokinet Biopharmaceut 4:499–519, 1976.

    CAS  Google Scholar 

  47. Blasberg RG, Groothuis DR, Molnar P: Application of quantitative Autoradiography in experimental brain tumors. Semin Neurol 1:203–221, 1981.

    Google Scholar 

  48. Groothuis DR, Blasberg RG, Molnar P, et al. Regional blood flow in avian sarcoma virus (ASV) induced brain tumors. Neurology 33: 686–696, 1983.

    PubMed  CAS  Google Scholar 

  49. Blasberg RG, Kobayashi T, Horowitz M, et al.: Regional blood flow in ethylnitrosourea (ENU) – induced brain tumors. Ann Neurol 14:189–201, 1983.

    PubMed  CAS  Google Scholar 

  50. Groothuis D, Pasternak J, Fischer J, et al.: Measurement of regional blood flow in RG-2 experimental brain tumors. Cancer Res 43: 3362–3367, 1983.

    PubMed  CAS  Google Scholar 

  51. Blasberg RG, Molnar P, Horowitz M, et al.: Regional blood flow in RT-9 brain tumors. J Neurosurg 58:863–873, 1983.

    PubMed  CAS  Google Scholar 

  52. Blasberg RG, Shapiro WR, Molnar P, et al.: Regional blood flow in Walker-256 metastatic brain tumors. J Neurooncol 2:195–204, 1984.

    PubMed  CAS  Google Scholar 

  53. Groothius DR, Molnar P, Blasberg RG: Regional blood flow and blood to tissue transport in five brain tumor models: Implications for chemotherapy. In Rosenblum M, Wilson C (eds), Progress in Experimental Tumor Research. (Volume 27), Brain Tumor Biology. Basel: S. Karger, 1984, pp 132–153.

    Google Scholar 

  54. Molnar P, Blasberg RG, Groothuis DR, et al.: Regional blood to tissue transport in avian sarcoma virus (ASV) induced brain tumors. Neurology 33:702–711, 1983.

    PubMed  CAS  Google Scholar 

  55. Blasberg R, Horowitz M, Rice J, et al.: Regional blood to tissue transport in ethylnitrosourea (ENU) induced brain tumors. Ann Neurol 14:202–215, 1983.

    PubMed  CAS  Google Scholar 

  56. Groothuis DR, Fischer JM, Pasternak JF, et al.: Regional Measurements of blood-to-tissue transport in experimental RG-2 rat gliomas. Cancer Res 43:3368–3373, 1983.

    PubMed  CAS  Google Scholar 

  57. Molnar P, Blasberg RG, Horowitz M, et al.: Regional blood to brain transport in RT-9 brain tumors. J Neurosurg 58:874–884, 1983.

    PubMed  CAS  Google Scholar 

  58. Blasberg RG, Shapiro WR, Molnar P, et al.: Regional blood to tissue transport in Walker-256 metastatic brain tumors. J Neurooncol 2:205–218, 1984.

    PubMed  CAS  Google Scholar 

  59. Levin VA, Patlak CS, Landahl HD: Heuristic modeling of drug delivery to malignant brain tumors. J Pharmakokinet Biopharmaceut 8: 257–296, 1980.

    CAS  Google Scholar 

  60. Brooks DJ, Beane RP, Lammertsma AA, et al.: Glucose transport across the blood brain barrier in normal subjects and patients with cerebral tumors studied using 11C-3-0-methyl-D-glucose and positron emission tomography. J Cereb Blood Flow Metab 6:230–329, 1986.

    PubMed  CAS  Google Scholar 

  61. Hawkins RA, Phelps ME, Huang SC, et al.: A kinetic evaluation of blood brain barrier permeability in human brain tumors with 68Ga-EDTA and positron emission tomography. J Cereb Blood Flow Metab 4:507–515, 1984.

    PubMed  CAS  Google Scholar 

  62. Brooks DJ, Beaney RP, Lammertsma AA, et al.: Quantitative measurement of blood brain permeability using 82Rb and positron emission tomography. J Cereb Blood Flow Metab 4:535–545, 1984.

    PubMed  CAS  Google Scholar 

  63. Yamamoto YL, Diksis M, Sako K, et al.: Pharmacokinetics and metabolic studies in human malignant gliomas. In Magistretti PL (ed), Functional Radionuclide Imaging of the Brain. New York: Raven Press, 1983, pp 327–335.

    Google Scholar 

  64. Hopewell J W: Importance of vascular damage in the development of late radiation effects in normal tissues. In Meyn E, Withers HR (eds), Radiation Biology in Cancer Research, New York: Raven Press, 1980, pp 449–459.

    Google Scholar 

  65. Hopewell JW: The late vascular effects of radiation. Br J Radiol 47:157–158, 1974.

    PubMed  CAS  Google Scholar 

  66. Young CMA: Functional and Neurological Changes in the Dermis of Pig Skin Following Surgery and X-irradiation. D Phil. Thesis, University of Oxford, United Kingdom, 1978.

    Google Scholar 

  67. Moustafa HF, Hopewell JW: Late functional changes in the vasculature of the rat brain after local X-irradiation. Br J Radiol, 1980.

    Google Scholar 

  68. Price RA, Birdwell DA: The central nervous system in childhood leukemia, III. Mineralizing microangiopathy and dystrophic calcification. Cancer 42:717–728, 1978.

    PubMed  CAS  Google Scholar 

  69. Harwood-Nash DCE, Reilley BJ: Calcification of the basal Ganglia following radiation therapy. Am J Roentgenol 108:392–395, 1970.

    CAS  Google Scholar 

  70. Price RA: Histopathology of central nervous system leukemia and complications of therapy. Am J Pediatr Hematol Oncol 1:21–30, 1979.

    PubMed  CAS  Google Scholar 

  71. McIntosh S, Fischer DB, Rothman S: Intracranial calcifications in childhood leukemia. J Pediatr 91:909–913, 1977.

    PubMed  CAS  Google Scholar 

  72. Poisson M, Pouillart P, Bataini JP, et al.: Malignant gliomas treated after surgery by combination chemotherapy and delayed irradiation, Part 1, Analysis of results. Acta Neurochir (Wein) 51:15–25, 1979.

    CAS  Google Scholar 

  73. Allen J, Helson L, Jereb B: Pre-radiation chemotherapy for newly diagnosed childhood brain tumors – A modified phase II trial. Cancer 52:2001–2206, 1982.

    Google Scholar 

  74. Griffin TW, Rasey JS, Bleyer WA: The effect of photon radiation on blood brain barrier permeability to methotrexate in mice. Cancer 40:1109–1111, 1977.

    PubMed  CAS  Google Scholar 

  75. Bleyer WA, Griffin TW: White matter necrosis, mineralizing microangiopathy, and intellectual abilities in survivors of childhood leukemia: associations with central nervous irradiation and methotrexate therapy. In Gilbert HA, Kagan AR (eds), Radiation Damage to the Nervous System. New York: Raven Press, 1980, pp 155–174.

    Google Scholar 

  76. Phillips TL: Clinical and experimental alterations in the radiation therapeutic ratio caused by cytotoxic chemotherapy. In Meyn RE, Withers HR (eds), Radiation Biology in Cancer Research. New York: Raven Press, 1980.

    Google Scholar 

  77. Bartelink H, Kallman RF, Rapaconietta D, Hart GAM: Therapeutic enhancement in mice by clinically relevant dose and fraction schedules of cis-diamminedichloroplatinum (II) and irradiation. Radiother Oncol 6: 61–74, 1986.

    PubMed  CAS  Google Scholar 

  78. Wheeler KT, Deen DF, Wilson CB, et al.: BCNU modification of the in vitro radiation response in 9L brain tumor cells in rats. Int J Radiat Oncol Biol Phys 2:79–88, 1977.

    PubMed  CAS  Google Scholar 

  79. Salazar OM, VanHoutte PJ, Bennett JM, et al.: High dose radiation therapy with low dose (pulsed) BCNU in malignant gliomas, an ECOG report. Int J Radiat Oncol Biol Phys 8:915–919, 1982.

    PubMed  CAS  Google Scholar 

  80. Alverez MV, Cobreros G, Heras A, Lopez-Zumel MC: Studies on cis-dichlorodiam-mineplatinum (II) as a radiosensitizer. Br J Cancer 37 (suppl 3):68–72, 1978.

    Google Scholar 

  81. Dritschilo A, Piro AJ, Delman AD: The effect of cis-platinum on the repair of radiation damage in plateau phase Chinese hamster (V-79) cells. Int J Radiat Oncol Biol Phys 5: 1345–1349, 1979.

    PubMed  CAS  Google Scholar 

  82. Stewart DJ, Leavens M, Maor M, et al.: Human central nervous distribution of CDDP and use as a radiosensitizer in malignant brain tumors. Cancer Res 42:2472–2479, 1982.

    Google Scholar 

  83. Mulne AF, Ruymann FB, Salgaller M, et al.: Sequencing of chemotherapy and radiotherapy for brain tumors in the human tumor stem cell assay. Proc Am Assoc Cancer Res 26:368, 1985.

    Google Scholar 

  84. Mulne AF, Salgaller ML, Walson PD, et al.: In vitro combination chemotherapy for brain tumors. Proc Fourth International Conference Human Tumor Cloning, Tucson, Arizona Health Sciences Center, Jan. 8–10, 1984, p. 71.

    Google Scholar 

  85. Rozental J, Finlay J, Trump D, Schutta H: Phase I study of 8 drugs in 1 day chemotherapy for primary brain tumors. Neurology 35 (Suppl 1):290–291, 1985.

    Google Scholar 

  86. Britt RH, Pounds DW, Lyons BE: Feasibility of treating malignant brain tumors with focused ultrasound. In Rosenblum ML, Wilson CB (eds), Progress in Experimental Tumor Research. Volume 28, Brain Tumor Therapy. Basel: Karger, 1984, pp 232–245.

    Google Scholar 

  87. Dewey WC, Holahan EV: Hyperthermia-basic biology. In Rosenblum ML, Wilson CB (eds), Progress in Experimental Tumor Research. Volume 28, Brain Tumor Therapy. Basel: Karger, 1984, pp 198–219.

    Google Scholar 

  88. Arcangeli G, Barni E., Cividalli A, et al.: Effectiveness of microwave hyperthermia combined with ionizing radiation: Clinical results on neck node metastastes. Int J Radiat Oncol Biol Phys 6:143–148, 1980.

    PubMed  CAS  Google Scholar 

  89. Manning MR, Cetas TC, Miller RC, et al.: Clinical hyperthermia: Results of phase I trial employing hyperthermia alone or in combination with external beam or interstitial radiotherapy. Cancer 49:205–216, 1982.

    PubMed  CAS  Google Scholar 

  90. Kim JH, Hahn EW, Tokita N, Nisce LZ: Local tumor hyperthermia in combination with radiation therapy. Cancer 40:161 – 169, 1977.

    PubMed  CAS  Google Scholar 

  91. Hornbeck NB, Shupe RE, Shidnia H, et al.: Preliminary clinical results of combined 433 MHz microwave therapy and radiation therapy on patients with advanced cancer. Cancer 40:2845–2863, 1977.

    Google Scholar 

  92. Hahn GM, Li GC: Interactions of hyperthermia and drugs: Treatment and probes. J Natl Cancer Inst Monogr 61:317–323, 1982.

    CAS  Google Scholar 

  93. Mann BD, Storm FK, Morton DL, et al.: Predictability of response to clinical thermo-chemotherapy by the clonogenic assay. Cancer 52:1389–1394, 1983.

    PubMed  CAS  Google Scholar 

  94. Hahn GM, Braun J, Harkedan I: Thermochemotherapy: synergism between hyperthermia and adriamycin or bleomycin in mammalian cell activation. Proc Natl Acad Sci USA 72:937–940, 1975.

    PubMed  CAS  Google Scholar 

  95. Thuning CA, Bakir NA, Warren J: Synergistic effect of combined hyperthermia and a nitrosourea in the treatment of a murine ependymoblastoma. Cancer Res 40:2726–2729, 1980.

    PubMed  CAS  Google Scholar 

  96. Stehlin JS, Giovanella BC, Ipolyi PD, et al.: Results of hyperthermic perfusion for melanoma of the extremities. Surg Gynecol Obstet 140:339–348, 1975.

    PubMed  CAS  Google Scholar 

  97. Storm FK, Silberman AW, Ramming KP et al.: Clinical thermochemotherapy: A controlled trial in advanced cancer patients. Cancer 53:863–868, 1984.

    PubMed  CAS  Google Scholar 

  98. Salcman M, Samaras GM: Interstitial microwave hyperthermia for brain tumors: Results of phase I clinical trial. J Neurooncol 1:225–236, 1983.

    PubMed  CAS  Google Scholar 

  99. Silberman AW, Rand RW, Storm FK, et al.: Phase I trial of thermochemotherapy for brain malignancy. Cancer 56:48–56, 1985.

    PubMed  CAS  Google Scholar 

  100. Sutton CH, Olinger R, Collazo L: Enhanced uptake of antineoplastic agents produced by microwave induced tumor hyperthermia and differential hypothermia in a murine glioma. Cryobiology 13:660, 1976.

    Google Scholar 

  101. Sutton CH: The use of local hyperthermia in brain tumor therapy. Proc Am Assoc Cancer Res 18:200, 1977.

    Google Scholar 

  102. Britt R, Lyons B, Pounds D, Prionas S: Feasibility of using ultrasound hyperthermia in the treatment of malignant brain tumors: Tissue damage threshold and thermal dosimetry studies. Med Instrum 17:172–177, 1983.

    PubMed  CAS  Google Scholar 

  103. Wise BL, Taxdal RR: Studies on the blood brain barrier utilizing hematoporphyrin. Brain Res 4:387–389, 1967.

    PubMed  CAS  Google Scholar 

  104. Diamond I, Granelli SG, McDonagh AF, et al.: Photodynamic therapy of malignant tumors. Lancet 2:1175–1177, 1972.

    PubMed  CAS  Google Scholar 

  105. Granelli SG, Diamond I, McDonagh AF, et al.: Photochemotherapy of glioma cells by visible light and hematoporphyrin. Cancer Res 35:2567–2570, 1975.

    PubMed  CAS  Google Scholar 

  106. Dougherty TJ, Kaufman JE, Goldfarb A, et al.: Photoradiation therapy for the treatment of malignant tumors. Cancer Res 38: 2628–2635, 1978.

    PubMed  CAS  Google Scholar 

  107. Perria C, Capuzzo T, Cavagnaro G: First attempts at the photodynamic treatment of human gliomas. J Neurosurg Sci 24:119–129, 1980.

    PubMed  CAS  Google Scholar 

  108. Laws ER, Cortese DA, Kinsey JH: Photo-radiation therapy in the treatment of malignant brain tumors, a phase I (feasibility) study. Neurosurgery 9:672–678, 1981.

    PubMed  Google Scholar 

  109. Wharen RE, Anderson RE, Laws ER: Quantitation of hematoporphyrin derivative in human gliomas, experimental CNS tumors and normal tissue. Neurosurgery 12:446–450, 1983.

    PubMed  Google Scholar 

  110. Cheng MK, McKean J, Boisvert D, et al.: Effects of photoradiation therapy on normal rat brain. Neurosurgery 15:804–810, 1984.

    PubMed  CAS  Google Scholar 

  111. Nowell PC: The clonal evolution of tumor cell populations. Science 194:23–28, 1976.

    PubMed  CAS  Google Scholar 

  112. Land H, Parada LF, Weinberg RA: Cellular oncogenes and multistep carcinogenesis. Science 222:771–778, 1983.

    PubMed  CAS  Google Scholar 

  113. Rowley JD: Human oncogene locations and chromosome aberrations. Nature 301: 290–291, 1983.

    PubMed  CAS  Google Scholar 

  114. Farber E: The multistep nature of cancer development. Cancer Res 44:4217–4223, 1984.

    PubMed  CAS  Google Scholar 

  115. Shapiro JR, Pu P-Y, Mohamed AN, et al.: Regional heterogeneity in high grade gliomas. Proc Am Assoc Cancer Res 25:375, 1984.

    Google Scholar 

  116. Bigner DD: Biology of Gliomas: Potential clinical implications of glioma cellular heterogeneity. Neurosurgery 9:320–326, 1981.

    PubMed  CAS  Google Scholar 

  117. Shapiro JR: Biology of gliomas: Heterogeneity, oncogenes, growth factors. Semin Oncol 13:4–15, 1986.

    PubMed  CAS  Google Scholar 

  118. Downward J, Yarden Y, Mayes E, et al.: Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature 307:521–527, 1984.

    PubMed  CAS  Google Scholar 

  119. Doolittle RF, Hunkapiller MW, Hood LE, et al.: Simian sarcoma virus one gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science 221: 275–277, 1983.

    PubMed  CAS  Google Scholar 

  120. Mohamed AN, Pu P-Y, Shapiro WR, et al.: Correlation of BCNU resistance in human glioma cells with overrepresentation of chromosome 22 and production of a factor resembling platelet-derived growth factor (PDGF). Proc Am Assoc Cancer Res 26:32, 1985.

    Google Scholar 

  121. Bertino JR: Toward improved selectively in cancer chemotherapy: The Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res 39:293–304, 1979.

    PubMed  CAS  Google Scholar 

  122. Yung W-Ka, Shapiro JR, Shapiro WR: Heterogeneous chemosensitivities of sub-populations of human glioma cells in culture. Cancer Res 42:992–998, 1982.

    PubMed  CAS  Google Scholar 

  123. Rankin JK, Yung W-Ka, Shapiro WR, et al.: Effects of low dose BCNU chemotherapy on human glioma cell lines in vitro. Proc Am Assoc Cancer Res 22:43, 1981.

    Google Scholar 

  124. Chelmicka-Schorr E, Arnason BGW, Holshouser SJ: C-6 glioma growth in rats, suppression with a B-adrenergic agonist and a phosphodiesterase inhibitor. Ann Neurol 8: 447–449, 1980.

    PubMed  CAS  Google Scholar 

  125. Chabner BA, Myers CE, Coleman CN, Johns DG: The clinical pharmacology of antineoplastic agents. N Egl J Med 292:1107–1113, 1975.

    CAS  Google Scholar 

  126. Chabner BA, Myers CE, Coleman CN, Johns DG: The clinical pharmacology of antineoplastic agents. N Egl J Med 292:1107–1113, 1159–1168, 1975.

    CAS  Google Scholar 

  127. Wilson EO, Eisner T, Briggs WR, et al.: Architecture of the cell. In Wilson EO, et al. (eds), Life on Earth. Sunderland, MA: Sinauer Associates Inc., 1978.

    Google Scholar 

  128. Kallman RF, Combs CA, Franko AJ, et al.: Evidence for the recruitment of noncycling clonogenic cells. In Meyn RE, Withers HR (eds), Radiation Biology in Cancer Research. New York: Raven Press, 1980.

    Google Scholar 

  129. Madoc-Jones H, Mauro F: Site of action of cytotoxic agents in the cell life cycle. In Antineoplastic and Immunosuppressive Agents, Volume 1. Heidelberg: Springer-Verlag, 1974, pp 205–219.

    Google Scholar 

  130. Hill BT, Baserga R: The cell cycle and its significance for cancer treatment, Cancer Treat Rev 2:159–175, 1975.

    PubMed  CAS  Google Scholar 

  131. Goldie JH, Price LA, Harrap KR: Methotrexate toxicity: Correlation with duration of administration, plasma levels, dose and excretion pattern. Eur J Cancer 8:409–414, 1972.

    PubMed  CAS  Google Scholar 

  132. Price LA, Goldie JH: Multiple drug therapy for disseminated malignant tumors. Br Med J 4:336–339, 1971.

    PubMed  CAS  Google Scholar 

  133. Skipper HE, Schabel FM Jr, Wilcox WS: Experimental evaluation of potential anticancer agents. XIII. on the criteria and kinetics associated with “curability” of experimental leukemia. Cancer Chemother Rep 35:3–111, 1964.

    Google Scholar 

  134. Vietti TJ, Valeriote FA: Conceptual basis for the use of chemotherapeutic agents and their pharmacology. Pediatr Clin North Am 23:1: 67–92, 1976.

    PubMed  CAS  Google Scholar 

  135. Bruce WR, Meeker BE, Valeroite FA: A comparison of the sensitivity of normal hemato-poetic and transplanted lymphoma colony forming cells to chemotherapeutic agents administered in vivo. J Natl Cancer Inst 37: 233–245, 1966.

    PubMed  CAS  Google Scholar 

  136. DeVita VT, Young RC, Canellos GP: Combination verses single agent chemotherapy: A review of the basis for selection of drug treatment of cancer. Cancer 35:98–110, 1975.

    PubMed  Google Scholar 

  137. Luria SE, Delbrück M: Mutations of bacteria from virus sensitivity to virus resistance. Genetics 28:491–511, 1943.

    PubMed  CAS  Google Scholar 

  138. Glassroth J, Robins AG, Snider DE Jr: Tuberculosis in the 1980’s N Engl J Med 302: 1441–1450, 1980.

    CAS  Google Scholar 

  139. Potter VR: Sequential blockade of metabolic pathways in vivo. Proc Soc Biol Med 76: 44–46, 1951.

    Google Scholar 

  140. Elion GB, Singer S, Hitchings GH: Antagonists of nuclei acid derivatives-VIII. Synergism in combinations of biologically related antimetabolites. J Biol Chem 208:477–478, 1954.

    PubMed  CAS  Google Scholar 

  141. Sartorelli AC: Some approaches to the therapeutic exploitation of metabolic sites of vulnerability of neoplastic cells. Cancer Res 29:2292–2299, 1969.

    PubMed  CAS  Google Scholar 

  142. Goldie JH, Coldman AJ: A mathematical model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep 63:1727–1733, 1979.

    PubMed  CAS  Google Scholar 

  143. Goldie JH: New thoughts on the resistance of chemotherapy. Hosp Pract [18]:165–177, 1983.

    CAS  Google Scholar 

  144. Goldie JH, Coldman AJ: Quantitative model for multiple levels of drug resistance in clinical tumors. Cancer Treat Rep 67:923–931, 1983.

    PubMed  CAS  Google Scholar 

  145. Curt GA, Clendeninn NJ, Chabner BA: Drug resistance in cancer. Cancer Treat Rep 68: 87–99, 1984.

    PubMed  CAS  Google Scholar 

  146. Peterson PHF, Meyers MD, Spengler BA, et al.: Alteration of plasma membrane glycoproteins and gangliosides of Chinese hamster ovary cells accompanying development of resistance to daunorubicin and vincristine. Cancer Res 43:222–225, 1983.

    PubMed  CAS  Google Scholar 

  147. Ling V, Thompson LH: Reduced permeability in CHO cells as a mechanism of resistance to colchicine. J Cell Physiol 83:103–116, 1973.

    Google Scholar 

  148. Pasten H, Gottesman MM: Molecular biology of multi-drug resistance in human cells. In Devita VT, Hellman S, Rosenberg SA (eds), Important Advances in Oncology. Philadelphia: J. B. Lippincott, 1988, pp 3–16.

    Google Scholar 

  149. Suzuki N, Kanno T, Nagata Y, Kato T: Inhibition of proliferative growth in glioma cells by galmodulin antagonists. J Neurosurg 65:74–79, 1986.

    PubMed  CAS  Google Scholar 

  150. Tsuruo T, Iida H, Nojiri M, et al.: Circumvention of vincristince and adriamycin resistance in vitro and vivo by calcium influx blockers. Cancer Res 43:2905–2910, 1983.

    PubMed  CAS  Google Scholar 

  151. Ewig RAG, Kohn KW: DNA damage and repair in mouse leukemia L1210 cells treated with nitrogen mustard, 1, 3-bis(2-chloroethyl)-1-nitrosourea, and other nitrosoureas. Cancer Res 37:2114–2122, 1977.

    PubMed  CAS  Google Scholar 

  152. Walker MD, Alexander E, Hunt WE, et al.: Evaluation of BCNU and or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg 49: 333–343, 1978.

    PubMed  CAS  Google Scholar 

  153. Rosenblum ML, Knebel KT, Vasquez DA, Wilson CB: Brain tumor therapy: quantitative analysis using a model system. J Neurosurg 46:145–154, 1977.

    PubMed  CAS  Google Scholar 

  154. Owellen RJ, Hartke CA, Dickerson RM, Hains FO: Inhibition of tubulin-microtubule polymerization by drugs of the vinca alkaloid class. Cancer Res 36:1499–1502, 1976.

    PubMed  CAS  Google Scholar 

  155. Rosenstock JG, Evans AE, Schut L: Response to vincristine of recurrent brain tumors in children. J Neurosurg 45:135–140, 1976.

    PubMed  CAS  Google Scholar 

  156. Razak A, et al.: Optimum time sequence for the administration of cyclophosphamide in vivo. Cancer Res 37:1857–1861, 1974.

    Google Scholar 

  157. Williams CJ, Whitehouse JMA: Cis-platinum: A new anticancer agent. Br Med J 1:1689–1691, 1979.

    PubMed  CAS  Google Scholar 

  158. Fravel HNA, Roberts JJ. G1 phase Chinese hamster V79–379A cells are inherently more sensitive to platinum bound to their DNA than mid S phase or asynchronously treated cells. Biochem Pharmacol 28:1575–1580, 1979.

    Google Scholar 

  159. Khan AB, D’Sousa BJ, Wharam MD, et al.: Cisplatin therapy in recurrent childhood brain tumors. Cancer Treat Rep 66:2013–2020, 1982.

    PubMed  CAS  Google Scholar 

  160. Sexauer CL, Khan A, Burger PC, et al.: Cisplatin in recurrent pediatric brain tumors, a Pediatric Oncology Group, phase III, study. Cancer 56:1497–1501, 1985.

    PubMed  CAS  Google Scholar 

  161. Allen JC, Walker R, Tan C: Carboplatin and recurrent brain tumors–high activity in medulloblastoma (abstract). Int Soc Pediat Oncol (SIOP) XVIII Annual Meeting, 1986.

    Google Scholar 

  162. Bergerat JP, Drewinko D, Lorry P, et al.: Synergistic lethal effect of cis-dichlorodiam-mine platinum and 1-beta-D-arabinofura-nosylcytosine. Cancer Res 41:25–30, 1981.

    PubMed  CAS  Google Scholar 

  163. Radice PA, Bunn PA, Ihde DC: Therapeutic trials with VP-16–213 and VM-26: active single agents in small cell lung cancer, non-hodgkin’s lumphoma and other malignancies. Cancer Treat Rep 63:1231–1239, 1979.

    PubMed  CAS  Google Scholar 

  164. Skylansky BD, Mann-Kaplan RS, Reynolds AF, et al.: 4’-dimethyl-epipodophyllotoxin-a-D-thenylideneglucoside (PTG) in the treatment of malignant intracranial neoplasms. Cancer 33:460–467, 1974.

    Google Scholar 

  165. Kessinger A, Lemon HM, Foley JF: VM-26 as a second line drug in the treatment of malignant gliomas. Proc Am Assoc Cancer Res 20:295, 1979.

    Google Scholar 

  166. Chou FL, Chan AH, Driscoll JS: Potential central nervous system antitumor agents. Aziridinylbenzoquinone. J Med Chem 19: 1302–1308, 1976.

    PubMed  CAS  Google Scholar 

  167. Clinical Brochure, AZQ, NSC 182986. Investigational Drug Branch. Cancer Therapy Evaluation Program. Division of Cancer Treatment. Bethesda, MD: National Cancer Institute, August 1979 (revised July 1983).

    Google Scholar 

  168. Savaraj N, Lu K, Feun LG, et al.: Intracerebral penetration and tissue distribution of 2, 5-diaziridinyl 3, 6-bis (carboethoxyamino) 1, 4-benzoquinone (AZQ, NSC-182986). J Neurooncol 1:15–19, 1983.

    PubMed  CAS  Google Scholar 

  169. Haid M, Khandekar JD, Christ M, et al.: Aziridinylbenzoquinone in recurrent, progressive glioma of the central nervous system, a phase II study by the Illinois Cancer Council. Cancer 56:1311–1315, 1985.

    PubMed  CAS  Google Scholar 

  170. Gutin PH, Levi JA, Wiernik PH, et al.: Treatment of malignant meningeal disease with intrathecal thiotepa: a phase II study. Cancer Treat Rep 61:885–887, 1977.

    PubMed  CAS  Google Scholar 

  171. Levin VA, Vestnys PA, Edwards MS, et al.: Improvement in survival produced by sequential therapies in the treatment of recurrent medulloblastoma. Cancer 51:1364–1370, 1983.

    PubMed  CAS  Google Scholar 

  172. Edwards MS, Levin VA, Saeger ML, et al.: Phase II evaluation of thiotepa for treatment of central nervous system tumors. Cancer Treat Rep 63:1419–1421, 1979.

    PubMed  CAS  Google Scholar 

  173. Gerosa M, DiStefano E, Carli M, Iraci G: Combined treatment of pediatric medulloblastoma. Childs Brain 6:262–273, 1980.

    PubMed  CAS  Google Scholar 

  174. McIntosh S, Chen M, Sartain PA, et al.: Adjuvant chemotherapy for medulloblastoma. Cancer 56:1316–1319, 1985.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  176. Bertino JR: Clinical pharmacology of methotrexate. Med Pediatr Oncol 10:401–411, 1982.

    PubMed  CAS  Google Scholar 

  177. Djerassi I, Kim JS, Shulman K: High dose methotrexate-citrovorum factor rescue in the management of brain tumors. Cancer Treat Rep 61:691–694, 1977.

    PubMed  CAS  Google Scholar 

  178. Djerassi I, Kim JS, Reggev A: Response of astrocytoma to high dose methotrexate with citrovorum factor rescue. Cancer 55: 2741–2747, 1985.

    PubMed  CAS  Google Scholar 

  179. Shapiro WR: High-dose methotrexate in malignant gliomas. Cancer Treat Rep 61: 753–756, 1977.

    PubMed  CAS  Google Scholar 

  180. Beckloff GL, Lerner HJ, Frost D, et al.: Hydroxyurea (NSC-32065) in biological fluids: Dose concentration relationships. Cancer Chemother Rep 48:57–58, 1965.

    PubMed  CAS  Google Scholar 

  181. Krakoff IH, Brown NC, Reichard P: Inhibition of ribonucleoside diphosphate reductase by hydroxyurea. Cancer Res 28:1559–1565, 1968.

    PubMed  CAS  Google Scholar 

  182. Piver MS, Howes AE, Suite HD, et al.: Effect of hydroxyurea on the radiation response of C3H mouse mammary tumors. Cancer 29: 407–412, 1972

    PubMed  CAS  Google Scholar 

  183. Irwin L, George F, Pitts F: Hydroxyurea (HU) and radiation therapy (RT) in primary intracranial malignant glial tumors. Proc Am Assoc Cancer Res ASCO 16:243, 1975.

    Google Scholar 

  184. Levin VA, Wilson CB, Davis R, et al.: A phase II comparison of BCNU, hydroxyurea and radiation therapy to BCNU and radiation therapy for the treatment of primary malignant gliomas. J Neurosurg 51:526–532, 1979.

    PubMed  CAS  Google Scholar 

  185. Walsh CT, Craig RW, Agarwal RP: Increased activation of 1-beta-D-arabino-furanosylcytosin by hydroxyurea and L-1210 cells. Cancer Res 40:3286–3292, 1980.

    PubMed  CAS  Google Scholar 

  186. Shiba DA, Weinkam RJ: Metabolic activation of procarbazine: Activity of intermediates and the effects of pretreatment. Proc Am Assoc Cancer Res 20:139, 1979.

    Google Scholar 

  187. Kumar ARV, Renaudin J, Wilson CB, et al.: Procarbazine hydrochloride in the treatment of brain tumors: Phase II study. J Neurosurg 40:365–371, 1974.

    Google Scholar 

  188. Walker MD, Green SB, Byar DP, et al.: Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant gliomas after surgery. N Engl J Med 303: 1323–1329, 1980.

    PubMed  CAS  Google Scholar 

  189. Lazarus HM, Herzig RH, Herzig GP, et al.: Central nervous system toxicity of high dose systemic cytosine arabinoside. Cancer 48: 2577–2582, 1981.

    PubMed  CAS  Google Scholar 

  190. Basier GA, Shapiro WR: Comparison of 2,2′-anhydro-l-b-D-arabinofuranosyl-5-flourocytosine and cytosine arabinoside in the treatment of murine brain tumor. Cancer Treat Rep 60:875–879, 1979.

    Google Scholar 

  191. Bogdahn U: Chemosensitivity of malignant human brain tumors: Preliminary results. J Neurooncol 1:149–166, 1983.

    PubMed  CAS  Google Scholar 

  192. Stewart DJ, Richard MT, Behoit B, et al.: Cisplatin and cytosine arabinoside in adults with malignant gliomas. J Neurooncol 2(1): 29–34, 1984.

    PubMed  CAS  Google Scholar 

  193. Kyriazis AP, Kyriazis AA, Martelo OJ: Response to single agent and combination chemotherapy of human pancreatic carcinoma grown in nude mice. Proc Am Assoc Cancer Res 22:211, 1981.

    Google Scholar 

  194. Breithaupt H, Dammann A, Aigner K: Pharmacokinetics of dacarbazine and its metabolite 5-aminoimidazole-4-carboxamide following different dose schedules. Cancer Chemother Pharmacol 9:103, 1982.

    PubMed  CAS  Google Scholar 

  195. Levin VA, Crafts D, Wilson CD, et al.: Imidazole carboxamides: Relationship of lipophilicity to activity against intracerebral murine glioma 26 and phase II clinical trial of 5-(3,3-bis(2-chloroethy 1)-1- triazeno) imida-zole-4-carboxamide (NSC-82196). Cancer Chemother Rep 59:327–331, 1975.

    PubMed  CAS  Google Scholar 

  196. De Vita VT, Serpick AA, Carbone PP: Combination chemotherapy in the treatment of advanced Hodgkin’s disease. Ann Intern Med 73:881–895, 1970.

    Google Scholar 

  197. Frias-Monserrate AE, VanEys J, Cangir A: Combined chemotherapy in the treatment of recurrent brain tumors. Proc Am Assoc Cancer Res ASCO 17:266, 1976.

    Google Scholar 

  198. Cangir A, VanEys J, Berry D: Combination chemotherapy with MOPP in children with recurrent brain tumors. Med Pediatr Oncol 4:253–261, 1978.

    PubMed  CAS  Google Scholar 

  199. VanEys J: Medical and oncologic management of pediatric brain tumors, Prog Exp Tumor Res 29:235–248, 1985.

    CAS  Google Scholar 

  200. Gutin PH, Wilson CB, Kumar ARV, et al.: Phase II study of procarbazine, CCNU and vincristine combination chemotherapy in the treatment of malignant brain tumors. Cancer 35:1398–1404, 1975.

    PubMed  CAS  Google Scholar 

  201. Hildebrand J, Brihaye J, Wagenknecht L, et al.: Combination therapy with CCNU, Vincristine and methotrexate in primary and metastatic brain tumors–A preliminary report. Eur J Cancer 9:627–634, 1973.

    PubMed  CAS  Google Scholar 

  202. Allen JC, Bloom J, Ertel I, et al: Brain tumors in children: Current cooperative and institutional chemotherapy trials in newly diagnosed and recurrent disease. Semin Oncol 13(1): 110–122, 1986.

    PubMed  CAS  Google Scholar 

  203. Finlay JL: Current status of the childrens cancer study group (CCSG) brain tumor trials. J Neurooncol 4:108 (abstract), 1986.

    Google Scholar 

  204. Bloom HJG: Intracranial tumors: responses and resistance to therapeutic endeavors, 1970–1980. Int J Pediatr Oncol Biol Phys 8:1083–1113, 1982.

    CAS  Google Scholar 

  205. Ertel I, Boesel C, Evans A, et al.: Adjuvant chemotherapy of high grade astrocytomas in children: Radiation therapy with or without CCNU, vincristine and prednisone. Proc Am Soc Clin Oncol ASCO 3:79, 1984.

    Google Scholar 

  206. Jenkin RDT, Boesel C, Ertel I, Evans A, et al.: Brain stem tumors in childhood: A prospective randomized trial of adjuvant treatment with chlorethylnitrosourea, vincristine and prednisone: Report of the Children Cancer Study Group. J Neurosurg 66:227–233, 1987.

    PubMed  CAS  Google Scholar 

  207. Goldie JH: New thoughts in resistance to chemotherapy. Hosp Pract 20:165–177, 1985.

    Google Scholar 

  208. Bleyer WA: “8 drugs in 1 Day” chemotherapy for brain tumors: a new approach and rationale for preradiation chemotherapy. Med Pediatr Oncol 11:213, 1983.

    Google Scholar 

  209. Pendergrass TW, Milstein MJ, Mulne AF, et al.: “8 drugs in 1 day” chemotherapy for brain tumors: Experience in 107 children and rationale for preradiation chemotherapy. J Clin Oncol 5:1221–1231, 1987.

    PubMed  CAS  Google Scholar 

  210. Zeltzer P, Odom L, Priest J, et al.: 8 drugs in one day (8-in-1) chemotherapy pre- and post-radiation for high risk medulloblastoma. (abstract). International society of paediatric oncology, SIOP, XVIII Annual Meeting, Belgrade, Yugoslavia: Sept. 15–20, 1986.

    Google Scholar 

  211. Sieverts H, Holldack J, Henze G, Bode U: Patients with relapsed brain tumors achieve complete remissions with “8-in-1” chemotherapy (abstract). Society of Paediatric Oncology, SIOP, XVIII Annual Meeting, Belgrade, Yugoslavia: Sept. 15–20, 1986.

    Google Scholar 

  212. Blasberg R, Molnar P, Groothuis D, Patlak C, Owens E, Fenstermacher J: Concurrent measurements of blood flow and transcapillary transport in avian sarcoma virus-induced experimental brain tumors–implications for chemotherapy. J Pharmacol Exp Ther 231(2): 724–735, 1984.

    PubMed  CAS  Google Scholar 

  213. Molnar P, Groothuis D, Blasberg R, Zaharko D, Owens E, Fenstermacher J: Regional thymidine transport and Incorporation in experimental brain and subcutaneous tumors. J. Neurochem 43(2):421–431, 1984.

    PubMed  CAS  Google Scholar 

  214. Rapoport SI, Ohno K, Fredericks WR, Pettigrew KD: Regional cerebrovascular permeability to (14C—) sucrose after osmotic opening of the blood-brain barrier. Brain Res 150: 653–657, 1978.

    PubMed  CAS  Google Scholar 

  215. Heuwelt EA, Barnett PA, Bigner DD, Frenkel EP: Effects of adrenal cortical steroids and osmotic blood-brain barrier opening on methotrexate delivery to gliomas in the rodent: The factor of the blood-brain barrier. Proc Natl Acad Sci USA 79:4420–4425, 1982.

    Google Scholar 

  216. Neuwelt EA, Howieson J, Frenkel EP, Specht D, Weigel R, et al.: Therapeutic efficacy of multi-agent chemotherapy with drug delivery enhancement by blood-brain barrier modification in glioblastoma. Neurosurgery 19:573–582, 1986.

    PubMed  CAS  Google Scholar 

  217. Neuwelt EA, Balaban E, Diehl J, Hill S, Frenkel E: Successful treatment of primary central nervous system lymphomas with chemotherapy after osmotic blood–brain barrier opening. Neurosurgery 12:662–671, 1983.

    PubMed  CAS  Google Scholar 

  218. Hiesiger EM, Voorhies RM, Basler GA, Lipschutz LE, Posner JB, Shapiro WR: Opening the blood-brain and blood-tumor barriers in experimental rat brain tumors: The effect of intracarotid hyperosmolar mannitol on capillary permeability and blood flow. Ann Neurol 19:50–59, 1986.

    PubMed  CAS  Google Scholar 

  219. Shapiro WR: Chemotherapy, animal models: Blood-brain barrier and pharmacology. Prog Exp Tumor Res 29:116–122, 1985.

    PubMed  CAS  Google Scholar 

  220. Levin VA, Landahl H, Patlak CS: Considerations in selecting effective brain tumor agents: Capillary permeability and sequestered cell populations. Proc Am Assoc Cancer Res ASCO 17:202 (Abstract #806), 1976.

    Google Scholar 

  221. Walker MD: Treatment of patients with supratentorial tumors–Astrocytomas, oligodendrogliomas, optic gliomas. In Kornblith PL, Walker MD, Cassady JR (eds), Neurologic Oncology. Philadelphia: Lippincott, 1987.

    Google Scholar 

  222. Solero CL, MonPardini S, Brambilla C, et al.: Controlled study with BCNU vs. CCNU as adjuvant chemotherapy following surgery plus radiotherapy for glioblastoma multiforme. Cancer Clin Trials, 2:43–48, 1979.

    PubMed  CAS  Google Scholar 

  223. Wasserman TH: Nitrosoureas: An outline of clinical schedules and toxic effects. Cancer Treat Rep 60:709–711, 1976.

    PubMed  CAS  Google Scholar 

  224. Bruce WR, Valeriote FA, Meeker BE: Survival of mice bearing a transplanted syngeneic lymphoma following treatment with cyclophosphamide, 5-fluorouracil or 1.3-bis (2-chloroethyl)-1-nitrosourea. J Natl Cancer Inst 39:257–266, 1967.

    PubMed  CAS  Google Scholar 

  225. Rosenblum ML, Dien DF, Hashiko T, Doughterty DA, Williams ME, Wilson CB: Comparison of clonagenic cell assays after in vivo and in vitro treatment of 9L gliosarcoma. Br J Cancer 41:307–308, 1980.

    Google Scholar 

  226. Wasserman TH, Comis RL, Goldsmith M, Handelsman H, Penta JS, Slavik M, et al.: Tabular analysis of the clinical chemotherapy of solid tumors. Cancer Chemother Rep 6:399, 1975.

    Google Scholar 

  227. Ansfield FJ, Ramirez G, Davis HL, Wirtanen GW, Johnson RO, Davis TE, et al.: Further clinical studies with intrahepatic artery infusion with 5-fluorouracil. Cancer 36:2413, 1975.

    PubMed  CAS  Google Scholar 

  228. Wiley AL, Wirtanen GW, Holden J, et al.: Utilization of a selective tumor artery catheterization technique for the intra-arterial delivery of chemotherapeutic agents and radiopharmaceuticals in a combined chemotherapy– radiotherapy clinical research program. In Radiobiological Research and Radiotherapy, volume I, Vienna: IAEA Pub No. ISBN 92-0-010377-4, 1977, pp 389–412.

    Google Scholar 

  229. Crafts DC, Levin VA, Nielsen S: Intracarotid BCNU (NSC-409962): A study of six rhesus monkeys. Cancer Treat Rep. 60:541–545, 1976.

    PubMed  CAS  Google Scholar 

  230. Levin VA, Kabra PM, Freeman-Dove MA: Pharmacokinetics of intracarotid artery 14C-BCNU in the squirrel monkey. J Neurosurg 48:587–593, 1978.

    PubMed  CAS  Google Scholar 

  231. Bullard DE, Bigner SH, Bigner DD: Comparison of intravenous versus intracarotid therapy with 1.3-bis (2-choroethyl)-1-nitrosourea in a rat brain tumor model. Cancer Res 45:5240–5245, 1985.

    PubMed  CAS  Google Scholar 

  232. West CR, Yamada K, Karakousis CP, et al.: Intra-arterial BCNU infusion for intracerebral metastasis from malignant melanoma plus lung cancer. Proc Am Assoc Cancer Res ASCO 20:332 (abstract), 1979.

    Google Scholar 

  233. Greenberg HS, Ensminger WD, Seeger JF, et al.: Intra-arterial BCNU chemotherapy for the treatment of malignant gliomas of the central nervous system: A preliminary report. Cancer Treat Rep 65:803–810, 1981.

    PubMed  CAS  Google Scholar 

  234. Magajewicz S, West CR, Park HC, et al.: Phase II study – intra-arterial BCNU therapy for metastatic brain tumors. Cancer 47: 653–657, 1981.

    Google Scholar 

  235. Hocheberg FH, Pruitt AA, Beck DO, DeBrun G, Davis K: The rationale and methodology for intra-arterial chemotherapy with BCNU as treatment for glioblastoma. J Neurosurg 63:876–880, 1985.

    Google Scholar 

  236. West CR, Avellanosa AM, Barva NR, Patel A, Hong CI: Intra-arterial 1.3-bis (2-Chloroethyl)-1-nitrosourea (BCNU) and systemic chemotherapy for malignant gliomas: A follow-up study. Neurosurgery 13:420–426, 1983.

    PubMed  CAS  Google Scholar 

  237. Yamashita J, Handa H, Tokuriki Y, Soo Y, Otsuka S-I, Suda K, Taki W: Intra-arterial ACNU therapy in malignant brain tumors. J Neurosurg 59:424–430, 1983.

    PubMed  CAS  Google Scholar 

  238. Wiley AL, Wirtanen GW, Joo P, Ansfield FJ, Ramirez G, Davis HL, Vermund H: Clinical and theoretical aspects of the treatment of surgically unresectable retroperitoneal malignancy with combined intra-arterial actinomycin-D and radiotherapy. Cancer 36:107–122, 1975.

    PubMed  Google Scholar 

  239. Mugal TI, Golde LM, Braun TJ, Klingen-smith W, Geier JM, Kindt GW: Phase I clinical trial of intracarotid bis-chloroethyl-nitrosourea (BCNU) and 21 dioxy-5-fluorou-ridine (FUDR) in malignant astrocytomas. J Neurooncol 3:291–296, 1986.

    Google Scholar 

  240. Stewart DJ, Grahovac Z, Benoit B, Addison D, Richard MT, DehneryJ, et al.: Intracarotid chemotherapy with a combination of 1.3-bis (2-chloroethyl)-1-nitrosourea (BCNU), cisdiaminedichloroplatinum (cisplatin), and 41–0-dimethyl-1-0-(4.6-0-2-thenylidine-B-D-glucopyranosyl) epipodophyllotoxin (VM-26) in the treatment of primary and metastatic brain tumors. Neurosurgery 15:828–833, 1984.

    PubMed  CAS  Google Scholar 

  241. Vance RB, Kapp JP: Supra-ophthalmic carotid infusion with low dose cisplatin and BCNU for malignant glioma. J Neurooncol 3:287–290, 1986.

    PubMed  CAS  Google Scholar 

  242. Mahaley MS, Whaley RA, Blue M, Bertsch L: Central neurotoxicity following intracarotid BCNU chemotherapy for malignant gliomas. J Neurooncol 3:297–314, 1986.

    PubMed  Google Scholar 

  243. Ommaya AK: Subcutaneous reservoir and pump for sterile access to ventricular cerebrospinal fluid. Lancet 2:983–984.

    Google Scholar 

  244. Fulton DS, Levin VA, Gutin PH, Edwards MSB, Seager ML, Stewart J, Wilson CB: Intrathecal cytosine arabinoside for the treatment of meningeal metastasis from malignant brain tumors and systemic tumors. Cancer Chemother Pharmacol 8:285–291, 1982.

    PubMed  CAS  Google Scholar 

  245. Blasberg RG: Methotrexate, cytosine arabinoside, and BCNU concentration in brain after ventriculocisternal perfusion. Cancer Treat Rep 61:625–621, 1977.

    PubMed  CAS  Google Scholar 

  246. Herzig RH, Fay JW, Herzig GP, et al.: High dose thiotepa and autologous marrow transplant. In Herzig GP (Symposium Chairman), Advances in Cancer Chemotherapy, Dallas, Texas: Park Row, Oct. 25, 1987.

    Google Scholar 

  247. Hildebrand J, Badjou R, Collard-Ronge, DelForge A, Malarme M, Spiro T, et al.: Treatment of brain gliomas with high dose of CCNU and autologous bone marrow transplantation. Biomedicine 32:71–75, 1980.

    PubMed  CAS  Google Scholar 

  248. Mortimer JE, Hewiett JS, Bay J, Livingston RB, et al.: High dose BCNU with autologous bone marrow rescue in the treatment of recurrent gliomas. J Neurooncol 1:269–273.

    Google Scholar 

  249. Hochberg FH, Parker LM, Takvorian T, Canellos GP, Zervas NT: High dose BCNU with autologous bone marrow rescue for recurrent glioblastoma multiforme. J Neurosurgery 54:455–460, 1981.

    CAS  Google Scholar 

  250. Phillips GL, Wolff SN, Fay JW, Herzig RH, Lazarus HM, Schold C, Herzig GP: Intensive 1.3-bis(2-chloroethyl)-1-nitrosourea (BCNU) monochemotherapy and autologous marrow transplantation for malignant glioma. J Clin Oncol 4:639–645, 1986.

    PubMed  CAS  Google Scholar 

  251. Carella AM, Giordano D, Santini G, et al.: High dose BCNU followed by autologous bone marrow infusion in glioblastoma multiforme. Tumori 67:473–475, 1981.

    PubMed  CAS  Google Scholar 

  252. Wolff SN, Fer MF, McKay CM, Hände KR, Hainsworth JD, Greco FA: High Dose VP-16-213 and autologous bone marrow transplantation for refractory malignancies: A phase I study. J Clin Oncol 1:701–705, 1983.

    PubMed  CAS  Google Scholar 

  253. Fingert HJ, Hochberg FH: Megadose chemotherapy with bone marrow rescue. Prog Exp Tumor Res 28:67–78, 1984.

    PubMed  CAS  Google Scholar 

  254. Nomura K, Watanabe T, Nakamura O, et al.: Intensive chemotherapy with autologous bone marrow rescue for recurrent malignant gliomas. Neurosurg Rev 7:13–22, 1984.

    PubMed  CAS  Google Scholar 

  255. Johnson DB, Smith MT, de los Reyes R, et al: Prolongation of survival with adjuvant chemotherapy of malignant glioma with high dose BCNU (HDBCNU) and autologous bone marrow transplantation (ABMTX). Proc Am Soc Clin Oncol 21:134 (abstract), 1985.

    Google Scholar 

  256. Hara T, Miyazaki S, Ishii E, Yoshida N, Inaba K, Ikeda K, Goya N: High dose 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloro-ethyl)-3-nitrosourea hydrochloride (ACNU) with autologous bone marrow rescue for patients with brain stem tumors. Childs Brain 11:369–374, 1984.

    PubMed  CAS  Google Scholar 

  257. Finlay JL, Dinndorf P, Sondel P, Longo W, Frierdich S: High dose thiotepa and VP-16 followed by autologous bone marrow “rescue” in the management of children and young adults with recurrent brain tumors: a pilot study (abstract). International Society of Pediatric Oncology, SIOP, XIX Meeting, Jerusalem, Sept. 13–18, 1987.

    Google Scholar 

  258. Finlay JL, Knipple J, Turski P, Levin A, Houston L, Rozental J, Egorin M: Pharmacokinetic studies of thio-tepa in dogs following delivery by various routes (abstract). Sixth International Conference on Brain Tumor Research and Therapy, Ashville, NC, 1985.

    Google Scholar 

  259. Bullard DE, Gillespie GY, Mahaley MS, Bigner DD: Immunobiology of human gliomas. Semin Oncol 13:94–109, 1986.

    PubMed  CAS  Google Scholar 

  260. Lundbald D, Lundgren E: Block of a glioma cell line in S by interferon. In J Cancer 27: 749–754, 1981,

    Google Scholar 

  261. Korosue K, Takeshita I, Monnoji H, Fukui M: Interferon effects on multiplication, cytoplasmic protein and GFAP content, and morphology in human glioma cells. J Neurooncol 1:69–76, 1983.

    PubMed  CAS  Google Scholar 

  262. Mahaley MS Jr, Urso MB, Whaley RA, Blue M, Williams TE, Guaspari A: Interferon as an adjuvant therapy with initial radiotherapy of patients with anaplastic gliomas. J Neurosurg 61:1069–1071, 1984.

    PubMed  Google Scholar 

  263. Mahaley MS Jr, Urso MB, Whaley RA, Blue M, Williams TE, Guaspari A, Selker RG: Therapeutic efficacy of interferon in the treatment of recurrent gliomas. J Neurosurg 63: 719–725, 1985.

    PubMed  Google Scholar 

  264. Duff TA, Borden E, Bay J, Piepmeier J, Sielaff K: Phase II trial of B-interferon for treatment of recurrent glioblastoma multiforme. J Neurosurg 64:408–413, 1986.

    PubMed  CAS  Google Scholar 

  265. Obbens AMT, Fern LG, Leavens ME, Savaraj N, Stewart DJ, Gutterman JU: Phase I clinical trial of intralesional and intraventricular leukocyte interferon for intracranial malignancies. J Neurooncol 3:61–67, 1985.

    PubMed  CAS  Google Scholar 

  266. Grimm EA, Mazumder A, Zhang HZ, et al: Lymphokine activated killer cell phenomenon, lysis of natural killer resistant fresh solid tumor cells by interleukin-2 activated autologous human peripheral blood lymphocytes. J Exp Med 155:1823–1841, 1982.

    PubMed  CAS  Google Scholar 

  267. Jacobs SK, Wilson DJ, Kornblith PL, Grimm EA: In vitro killing of human glioblastoma by interleukin-2 activated autologous lymphocytes. J Neurosurg 64:114–117, 1986.

    PubMed  CAS  Google Scholar 

  268. Jacobs SK, Wilson, DJ, Kornblith, PL, Grimm, EA: Interleukin-2 and autologous lymphokine-activated killer cells in the treatment of malignant glioma. J Neurosurg 64:743–749, 1986.

    PubMed  CAS  Google Scholar 

  269. Jacques DB, Ingram, M Sheldon CH, Freshwater DB, Skillen RG, Techy GB: Immunotherapy of malignant brain tumors using cultured autologous lymphocytes (abstract). Am College of Surgeons, Neurosurgery Division, Palm Springs, CA, Feb. 1986.

    Google Scholar 

  270. Bourdon MA, Coleman RE, Bigner DD: The potential of monoclonal antibodies as carriers of radiation and drugs for immunodetection and therapy of brain tumors. Prog Exp Tumor Res 28:79–101, 1984.

    PubMed  CAS  Google Scholar 

  271. Mahaley MS Jr, Day ED: Immunological studies in human gliomas. J Neurosurg 23: 363–370, 1965.

    PubMed  Google Scholar 

  272. Kohler G, Milstein C: Continuous cultures of fused cells secreting antibodies of predefined specificity. Nature 256:494–497, 1975.

    Google Scholar 

  273. Baldwin RW: Monoclonal antibodies for targeting chemotherapeutic agents. Prog Exp Tumor Res 29:140–151, 1985.

    PubMed  CAS  Google Scholar 

  274. Embleton M, Rowland G, Simmonds R, et al.: Selective cytotoxicity against human tumor cells by a vindesine-monoclonal antibody conjugate. Br J Cancer 47:43–49, 1983.

    PubMed  CAS  Google Scholar 

  275. Carnett M, Embleton M, Jacobs E, Baldwin R: Preparation and properties of a drug carrier conjugate showing selective antibody-directed cytotoxicity in vitro. Int J Cancer 31:661–670, 1983.

    Google Scholar 

  276. Dullens HFJ, Vennegoor D, DeWeger RA, et al.: Comparison of various forms of therapies in two different mouse tumor systems. Cancer Treat Rep 63:99–109, 1979.

    PubMed  CAS  Google Scholar 

  277. Tsukada Y, Bischof WKD, Hini N, et al.: Effect of a conjugate of daunomycin with antibodies to rat alpha-fetoprotein on the growth of alpha-fetoprotein producing cells. Proc Natl Acad Sci USA 79:621–625, 1982.

    PubMed  CAS  Google Scholar 

  278. Ettinger DS, Order SE, Wharam MD, et al.: Phase I-II study of isotopic immunoglobulin therapy for primary liver cancer. Cancer Treat Rep 66:289–297, 1982.

    PubMed  CAS  Google Scholar 

  279. Lashford LS, Coakham HB, Davies G, Jones DH, Kemshead JT: Targeted intrathecal radiation using monoclonal antibodies for malignant meningitis. SIOP, XVIII Annual Meeting, Belgrade, Yugoslavia, Sept. 15–20, 1986.

    Google Scholar 

  280. Courtenay-Luck N, Epenelos AA, Hainan KE, et al.: Antibody guided irradiation of malignant lesions: Three cases illustrating a new method of treatment. Lancet: 1:1441–1443, 1984.

    Google Scholar 

  281. Mizusawa E, Dahlman HL, Bennett SJ, Goldenberg DM, Hawthorne MF: Neutron-capture therapy of human cancer: In vitro results on the preparation of boron-labelled antibodies to carcinoembryonic antigen. Proc Nat Acad Sci USA 79:3011–3014, 1982.

    PubMed  CAS  Google Scholar 

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Authors
  1. Jeffrey A. Stephenson
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  2. Jonathon L. Finlay
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Editors and Affiliations

  1. Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA

    Melvin Deutsch M.D. (Professor) (Professor)

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© 1990 Kluwer Academic Publishers

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Stephenson, J.A., Finlay, J.L. (1990). Pathophysiologic Basis for Brain Tumor Chemotherapy. In: Deutsch, M. (eds) Management of Childhood Brain Tumors. Foundations of Neurological Surgery, vol 3. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1501-8_8

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  • DOI: https://doi.org/10.1007/978-1-4613-1501-8_8

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