Principles of Chemotherapy in Brain Neoplasia

  • Mary K. Gumerlock
  • E. A. Neuwelt


For the neurooncologic clinician, brain tumors, be they primary or secondary, are a frustrating challenge. Successful therapy often is not achieved with surgery or radiation therapy. One is therefore faced with the choice of chemotherapy, itself currently a less than adequate answer. Also, for the neuroclinician, such a choice is at once intimidating. It is the purpose, then, of this chapter to put brain tumor chemotherapy into clinical perspective, beginning first with the basic principles of anticancer drug therapy, continuing through an organized schema of the currently available chemotherapeutic agents as applicable to neurooncology and applying these to the specific features of brain tumors. The focus is to work through various research angles to distill the clinically relevant perspectives of this vast subject.


Brain Tumor Brain Metastasis Clin Oncol Primary Brain Tumor Malignant Brain Tumor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Abramowicz H (1985) Cancer chemotherapy. Med Lett Drugs Ther 27: 13 – 20Google Scholar
  2. 2.
    Abelson HT, Kufe DW, Skarin AT, et al.(1981) Treatment of central nervous system tumors with methotrexate. Cancer Treat Rep 65: 137 – 140PubMedGoogle Scholar
  3. 3.
    Alavi JB, Weiler CB, Bruno LA (1984) Phase II evaluation of vindesine in the treatment of malignant glioma. Cancer Treat Rep 68: 807 – 808PubMedGoogle Scholar
  4. 4.
    Allen JC, Helson L (1981) High-dose cyclophosphamide chemotherapy for recurrent CNS tumors in children. J Neurosurg 55: 749 – 756PubMedGoogle Scholar
  5. 5.
    Allen JC, Helson L, Jereb B (1983) Preradiation chemotherapy for newly diagnosed childhood brain tumors: a modified phase II trial. Cancer 52: 2001 – 2006PubMedGoogle Scholar
  6. 6.
    Allen JC, Bosl G, Walker R (1984) Chemotherapy trials in recurrent CNS germ cell tumors. Proc Am Soc Clin Oncol 3: 325Google Scholar
  7. 7.
    Allen JC (1985) Childhood brain tumors. Current status of clinical trials in newly diagnosed and recurrent disease. Pediatr Clin North Am 32: 633 – 651PubMedGoogle Scholar
  8. 8.
    Amadori S, Papa G, Avisati G, et a. (1984) Sequential combination of systemic high-dose ara-C and asparaginase for the treatment of central nervous system leukemia and. lymphoma. J Clin Oncol 2: 98 – 101PubMedGoogle Scholar
  9. 9.
    Andersen J, Christensen L, Kongsholm H (1984) Phase II trial of prednimustine in glioblastoma multiforme. Cancer Treat Rep 68: 795 – 797PubMedGoogle Scholar
  10. 10.
    Ariel IM (1961) Intra-arterial chemotherapy for metastatic cancer to the brain. Am J Surg 102: 647 – 650PubMedGoogle Scholar
  11. 11.
    Avellanosa A, West C, Barua N, Patel A (1984) Intracavitary combination chemotherapy of recurrent malignant glioma via Ommaya shunt—A pilot study. Proc Am Soc Clin Oncol 2: 234Google Scholar
  12. 11.
    a. Barnett MJ, Ganesan TS, Waxman JH, et al. (1985) Central nervous system toxicity of high-dose cytosine arabinoside. Sem Oncol 12 [suppl] 3: 227 – 232Google Scholar
  13. 12.
    Bauer KA, Skarin AT, Balikian JP, et a. (1983) Pulmonary complications associated with combination chemotherapy programs containing bleomycin. Am J Med 74: 557–563Google Scholar
  14. 13.
    Becker LE. Hinton D (1983) Primitive neuroectodermal tumors of the central nervous system. Human Pathol 14: 538 – 550Google Scholar
  15. 14.
    Benger A, Browman GP, Walker IR, Preisler HD, Goldberg J (1985) Clinical evidence of a cumulative effect of high-dose cytarabine on the cerebellum in patients with acute leukemia: a leukemia intergroup report. Cancer Treat Rep 69: 240 – 241PubMedGoogle Scholar
  16. 15.
    Berd D, Maguire HC, Mastrangelo MJ (1984) Potentiation of human cell-mediated and humoral immunity by low-dose cyclophosphamide. Cancer Res 44: 5439 – 5443PubMedGoogle Scholar
  17. 16.
    Berman IJ, Mann MP (1980) Seizures and transient cortical blindness associated with cisplatinum (II) diamminedichloride ( PDD) therapy in a thirty year old man. Cancer 45: 764–766PubMedGoogle Scholar
  18. 17.
    Berry MP, Simpson WJ (1981) Radiation therapy in the management of primary malignant lymphoma of the brain. Int J Radiat Oncol Biol Phys 7: 55 – 59PubMedGoogle Scholar
  19. 18.
    Bigotte L, Arvidson B, Olsson Y (1982) Cytofluorescence localization of adriamycin in the nervous system. I. Distribution of the drug in the central nervous system of normal adult mice after intravenous injection. Acta Neuropathol (Berl) 57: 121–129Google Scholar
  20. 19.
    Bigotte L, Arvidson B, Olsson Y (1982) Cytofluorescence localization of adriamycin in the nervous system. II. Distribution of the drug in the somatic and autonomic peripheral nervous systems of normal adult mice after intravenous_ injection. Acta Neuropathol (Berl) 57: 130–136Google Scholar
  21. 20.
    Blacklock JB, Wright DC, Dedrick TL, et a. (1985) Drug streaming during intraarterial chemotherapy. Sixth international conference on brain tumor research and therapy, Asheville (abstract)Google Scholar
  22. 21.
    Blasberg RG, Nakagawa H, Patlak CS, Groothuis DR (1985) Dexamethasone reduces tumor and brain extracellular space: Effects on edema propagation. J Neuro-Oncol, 2: 227Google Scholar
  23. 22.
    Bleyer WA, Griffin TW (1980) White matter necrosis, mineralizing microangiopathy, and intellectual abilities in survivors of childhood leukemia. In: Gilbert HA, Kagan AR (eds) Radiation damage to the nervous system. A delayed therapeutic hazard. Raven Press, New York, pp 155 – 174Google Scholar
  24. 23.
    Bleyer WA, Milstein J, Balis F, et a. (1983) “8 drugs in 1 day” chemotherapy for brain tumors: a new approach and rationale for preradiation chemotherapy. Med Pediatr Oncol 11: 213Google Scholar
  25. 24.
    Bosl GJ, Yagoda A, Golbey RB, Whitmore W, et a. (1985) Role of etoposide-based chemotherapy in the treatment of patients with refractory or relapsing germ cell tumors. Am J Med 78: 423 – 428PubMedGoogle Scholar
  26. 25.
    Bourdon MA, Coleman RE, Bigner DD (1984) The potential of monoclonal antibodies as carriers of radiation and drugs for immunodetection and therapy of brain tumors. Prog Exp Tumor Res 28: 79 – 101PubMedGoogle Scholar
  27. 26.
    Bradbury M (1979) The concept of a blood-brain barrier. J Wiley, New YorkGoogle Scholar
  28. 27.
    Broman T, Olsson O (1948) The tolerance of cerebral blood-vessels to a contrast medium of the diodrast group. Acta Radiol 30: 326 – 342Google Scholar
  29. 28.
    Broman T, Olsson O (1949) Experimental study of contrast media for cerebral angiography with reference to possible injurious effects on the cerebral blood vessels. Acta Radiol 31: 321 – 334PubMedGoogle Scholar
  30. 29.
    Brugarolas A, Garcia, de Sola R, Bravo G et a. (1980) Intra-arterial quelamycin in the treatment of glioblastoma. Proc Am Assoc Cancer Res 21: 346Google Scholar
  31. 30.
    Buckley JE, Clark VL, Meyer TJ, Pearlman NW (1984) Hypomagnesemia after cisplatin combination chemotherapy. Arch Intern Med 144: 2347 – 2348PubMedGoogle Scholar
  32. 31.
    Budka H (1982) Pathology of encephalopathies induced by treatment or prophylaxis of neoplastic lesions of the nervous system. In: Hildebrand J, Gangji D (eds) Treatment of neoplastic lesions of the nervous system. Pergamon Press, New York, pp 45 – 50Google Scholar
  33. 32.
    Burger PC, Kamenar E, Schold SC, et a. (1981) Encephalomyelopathy following high-dose BCNU therapy. Cancer 48: 1318 – 1327Google Scholar
  34. 33.
    Burger PC, Vogel FS, Green SB, Strike TA (1985) Glioblastoma multiforme and anaplastic astrocytoma: Pathologic criteria and prognostic implications. Cancer 56: 1106–1111Google Scholar
  35. 34.
    Butti G, Knerich R, Tanghetti B, et a. (1984) Perioperative carmustine chemotherapy for malignant brain tumors. Cancer Treat Rep 68: 1505 – 1506PubMedGoogle Scholar
  36. 35.
    Calabresi P, Parks RE (1985) Chemotherapy of neoplastic diseases. In: Gilman AG, Goodman LS, Gilman A (eds) The pharmacological basis of therapeutics. Macmillan, New York, pp 1240 – 1306Google Scholar
  37. 36.
    Cangir A, Ragab AH, Steuber P, et al. (1984) Combination chemotherapy with vincristine (NSC-67574), procarbazine (NSC-77213), prednisone (NSC-1 0023) with or without nitrogen mustard (NSC-762) ( MOPP vs OPP) in children with recurrent brain tumors. Med Ped Oncol 12: 1–3Google Scholar
  38. 37.
    Capizzi RL, Nichols R, Mullins J (1972) Long-term survival of leukemic mice by therapeutic synergism between asparaginase and methotrexate. Fed Proc 31: 553Google Scholar
  39. 38.
    Carey RW, Davis JM, Zervas NT (1981) Tamoxifen-induced regression of cerebral metastases in breast carcinoma. Cancer Treat Rep 65: 793 – 795PubMedGoogle Scholar
  40. 39.
    Carmichael SM, Eagleton L, Ayers CR, et al. (1970) Orthostatic hypotension during vincristine therapy. Arch Intern Med 126: 290 – 293PubMedGoogle Scholar
  41. 40.
    Casanova MF (1984) Vasogenic edema with intraparenchymatous expanding mass lesions: A theory on its pathophysiology and mode of action of hyperventilation and corticosteroids. Med Hypotheses 13: 439 – 450PubMedGoogle Scholar
  42. 41.
    Chang CH, Horton J, Schoenfeld D, et al. (1983) Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas. Cancer 52: 2297 – 1007Google Scholar
  43. 42.
    Clark AW, Cohen SR, Nissenblatt MJ, Wilson SK (1982) Paraplegia following intrathecal chemotherapy: neuropathologic findings and elevation of myelin basic protein. Cancer 50: 42 – 47PubMedGoogle Scholar
  44. 43.
    Coscarelli C, Heinrich RL, Ganz PA (1984) Karnofsky performance status revisited: Reliability, validity and guidelines. J Clin Oncol 2: 187–193Google Scholar
  45. 44.
    Crafts DC, Levin VA, Edwards MS, Pischer TL, Wilson CB (1978) Chemotherapy of recurrent medulloblastoma with combined procarbazine, CCNU, and vincristine. J Neurosurg 49: 589–592PubMedGoogle Scholar
  46. 45.
    Dakhil S, Ensminger W, Strother V, et al. (1981) Pharmacokinetics of intraventricular 5-fluoro-2-deoxiuridine ( FUDR) in patients with meningeal neoplasia. Proc Am Assoc Cancer Res 22: 178Google Scholar
  47. 46.
    Davis PL, Shumway MH (1961) Thio-tepa in treatment of metastatic cerebral malignancy. JAMA 175: 714 – 175PubMedGoogle Scholar
  48. 47.
    Dedrick RL, Oldfield EH, Collins JM (1984) Arterial drug infusion with extracorporeal removal. I. Theoretic basis with particular reference to the brain. Cancer Treat Rep 68: 373–380Google Scholar
  49. 48.
    Delaney WE, Antoniades J (1985) Combination radiation/cisplatinum for adult malignant gliomas. Proc Am Soc Clin Oncol 4: 522Google Scholar
  50. 49.
    De Vita VT (1985) Principles of chemotherapy. In: DeVita ST, Hellman S, Rosenberg SA (eds) Cancer: principles and practice of oncology. JB Lippincott, Philadelphia, pp 257 – 285Google Scholar
  51. 50.
    De Vita VT (1983) The relationship between tumor mass and resistance to chemotherapy. Cancer 1: 1209 – 1220Google Scholar
  52. 51.
    Dick SJ, Macchi B, Papazoglou S, et al. (1983) Lymphoid cell glioma cell interaction enhances cell coat production by human gliomas: Novel suppressor mechanism. Science 220: 739–742Google Scholar
  53. 52.
    Djerassi I, Kim JS, Reggev A (1985) Response of astrocytoma to high-dose methotrexate with citrovorum factor rescue. Cancer 55: 2741 – 2747PubMedGoogle Scholar
  54. 53.
    Doll DC, Weiss RB, Issell BF (1985) Mitomycin: Ten years after approval for marketing. J Clin Oncol 3: 276–286PubMedGoogle Scholar
  55. 54.
    Duffy PE (1983) Astrocytes: normal, reactive, and neoplastic. Raven Press, New YorkGoogle Scholar
  56. 55.
    Dworkin LA, Goldman RD, Zivin LS, Fuchs PC (1985) Cerebellar toxicity following high-dose cytosine arabinoside. J Clin Oncol 3: 613 – 616PubMedGoogle Scholar
  57. 56.
    Eagen RT, Scott MS (1983) Evaluation of prognostic factors in chemotherapy of recurrent brain tumors. J Clin Oncol 1: 38 – 44Google Scholar
  58. 57.
    Eagen RT, Dinapoli RP, Hermann RC, Groover RV, Layton DD (1984) Carmustine and Baker’s antifol combination chemotherapy for primary brain tumors progressive after irradiation and chemotherapy. Cancer Treat Rep 68: 431Google Scholar
  59. 58.
    Edwards MS, Levin VA, Seager ML, Pischer TL, Wilson CB (1979) Phase II evaluation of thioTEPA for treatment of central nervous system tumors. Cancer Treat Rep 63: 1419 – 1421PubMedGoogle Scholar
  60. 59.
    Edwards MS, Levin VA, Wilson CB (1980) Brain tumor chemotherapy: An evaluation of agents in current use for phase II and III trials. Cancer Treat Rep 64: 1179–1205Google Scholar
  61. 60.
    Edwards MS, Levin VA, Seager ML, Wilson CB (1981) Intrathecal chemotherapy for leptomeningeal dissemination of medulloblastoma. Child’s Brain 8: 444 – 451PubMedGoogle Scholar
  62. 61.
    Einhorn LH (1980) Chemotherapy of metastatic seminoma. In: Einhorn H (ed) Testicular tumors: management and treatment. Masson, New York, pp 151 – 167Google Scholar
  63. 62.
    Epenetos AA, Courtenay-Luck N, Pickering D, et al. (1985) Antibody guided irradiation of brain glioma by arterial infusion of radioactive monoclonal antibody against epidermal growth factor receptor and blood group A antigen. Br Med J 290: 1463 – 1466Google Scholar
  64. 63.
    Ervin T, Canellos GP (1980) Successful treatment of recurrent primary central nervous system lymphoma with high-dose methotrexate. Cancer 45: 1556 – 1557PubMedGoogle Scholar
  65. 64.
    Fenstermacher J, Gazendam J (1981) Intra-arterial infusions of drugs and hyperosmotic solutions as ways of enhancing CNS chemotherapy. Cancer Treat Rep 65: 27 – 37PubMedGoogle Scholar
  66. 65.
    Fenstermacher JD (1985) Current models of blood-brain transfer. Trends in Neurosciences 8: 449 – 453Google Scholar
  67. 66.
    Fernandes DJ, Bertino JR (1980) 5-fluorouracil-methotrexate synergy: Enhancement of 5-fluorodeoxyuridylate binding to thymidylate synthase by dihydropteroyl poly-glutamates. Proc Natl Acad Sci 77: 5664 – 5667Google Scholar
  68. 67.
    Feun LG, Wallace S, Lee F, et al. (1983) Phase I trial of intracarotid VP-16–213 ( Etoposide) in patients with intracerebral tumors. Proc Am Soc Clin Oncol 2: 238Google Scholar
  69. 68.
    Feun LG, Wallace S, Yung WKA, et al. (1984) Phase I-II trial of intracarotid (IC) BCNU and cisplatin in patients with intracerebral tumors ( ICT ). Proc Am Soc Clin Oncol 3: 999Google Scholar
  70. 69.
    Feun LG, Lee YY, Yung WKA (1985) Phase II trial of intracarotid (IC) BCNU and cisplatin ( DDP) in malignant brain tumors. Proc Am Soc Clin Oncol 4: 585Google Scholar
  71. 70.
    Fingert HJ, Hochberg FH (1984) Megadose chemotherapy with bone marrow rescue. Prog Exp Tumor Res 28: 67 – 78PubMedGoogle Scholar
  72. 71.
    Finlay JL, Knipple J, Turski P, et al. (1985) Pharmacokinetic studies of thio-tepa in dogs following delivery by various routes. Sixth international conference on brain tumor research and therapy, Asheville (abstract)Google Scholar
  73. 72.
    Firth G, Oliver AS, McKeran RO (1984) Studies on the intracerebral injection of bleomycin free and entrapped within liposomes in the rat. J Neurol Neurosurg Psychiat 47: 585 – 589PubMedGoogle Scholar
  74. 73.
    Firth G, Oliver AS, McKeran RO (1984) Studies on the use of antimitotic drugs entrapped within liposomes and of their action on a human glioma cell line. J Neurol Sci 63: 153 – 165PubMedGoogle Scholar
  75. 74.
    Flombaum CD (1984) Hypomagnesemia associated with cisplatin combination chemotherapy. Arch Intern Med 144: 2336 – 2337PubMedGoogle Scholar
  76. 75.
    Flora KP, Cradock JC, Kelley JA (1982) The hydrolysis of spirohydantoin mustard. J Pharm Sci 71: 1206 – 1211PubMedGoogle Scholar
  77. 76.
    Folkman J (1984) What is the role of endothelial cells in angiogenesis? Lab Invest 51: 601 – 604PubMedGoogle Scholar
  78. 77.
    Folkman J (1985) Tumor angiogenesis. Adv Cancer Res 43: 175 – 203PubMedGoogle Scholar
  79. 78.
    Foo S-H, Ransohoff J, Berenstein A, Choy I-S (1985) Intra-arterial BCNU chemotherapy for malignant gliomas. J Neurosurg 62: 458 – 459PubMedGoogle Scholar
  80. 79.
    Friedman MA (1981) Phase I and II studies of PCNU. In: Prestayko AW, et al. (eds) Nitrosoureas: current status and new development. Academic Press, New York, pp 379 – 386Google Scholar
  81. 80.
    Frytak S, Earnest F, O’Neill BP, Lee RE (1985) Nuclear magnetic resonance scanning (NMRS) for neurotoxicity (NT) in long term survivors of carcinoma ( CA ). Proc Am Soc Clin Oncol 4: 515Google Scholar
  82. 81.
    Fulling KH, Garcia DM (1985) Anaplastic astrocytoma of the adult cerebrum. Cancer 55: 928 – 931PubMedGoogle Scholar
  83. 82.
    Gagliano RG, Costanzi JJ (1976) Paraplegia following intrathecal methotrexate. Cancer 37: 1663 – 1668PubMedGoogle Scholar
  84. 83.
    Galivan J, Nimec Z (1984) Effects of folic acid on hepatoma cells containing methotrexate polyglutamates. Cancer Res 43: 551 – 555Google Scholar
  85. 83.
    a. Gamache FW, Galicich JH, Posner JB (1980) Treatment of brain metastasis by surgical extirpation. In: Weiss L, Gilbert HA, Posner JB (eds) Brain metastasis. G. K. Hall, Massachusetts, pp 390 – 414Google Scholar
  86. 84.
    Garbino CE, Gordon-Firing S (1984) Adjuvant chemotherapy with VM26 in glioblastoma multiforme. Proc Am Soc Clin Oncol 3: C997Google Scholar
  87. 85.
    Giangaspero F, Burger PC (1983) Correlations between cytologic composition and biologic behavior in the glioblastoma multiforme. Cancer 52: 2320 – 2333PubMedGoogle Scholar
  88. 86.
    Goldman ID, Fyfe M (1974) The mechanism of action of methotrexate: II. Augmentation by vincristine of inhibition of deoxyribonucleic acid synthesis by methotrexate in Ehrlich ascites tumor cells. Mol Pharmacol 10: 275–282PubMedGoogle Scholar
  89. 87.
    Green SB, Byar DP, Walker MD, et al. (1983) Comparisons of carmustine, procarbazine, and high-dose methylprednisolone as additions to surgery and radiotherapy for the treatment of malignant glioma. Cancer Treat Rep 67: 121 – 132PubMedGoogle Scholar
  90. 88.
    Green SB, Byar DP, Strike TA, et al. (1984) Randomized comparisons of BCNU, streptozotocin, radio-sensitizer, and fractionation of radiotherapy in the postoperative treatment of malignant glioma (Study 7702), Proc Am Soc Clin Oncol 3: C 1018Google Scholar
  91. 89.
    Green SB, Byar DB, Strike TA, et al. (1985) Randomized phase II comparison of PCNU and AZQ for the treatment of primary brain tumors (Study 8120). Proc Am Soc Clin Oncol 4: C 558Google Scholar
  92. 90.
    Greenberg HS, Ensminger W, Chandler WF, et al. (1984) Intra-arterial BCNU chemotherapy for treatment of malignant gliomas of the central nervous system. J Neurosurg 61: 423 – 429PubMedGoogle Scholar
  93. 91.
    Greenberg HS, Ensminger W, Layton P, Gebarski S. Meyer MB (1984) A phase 1–2 evaluation of intra-arterial diaziquone (AZQ) for malignant tumors of the central nervous system. Proc Am Soc Clin Oncol 3: C 1003Google Scholar
  94. 92.
    Greig NH (1984) Chemotherapy of brain metastases: Current status. Cancer Treat Rev 11: 157 – 186PubMedGoogle Scholar
  95. 93.
    Greig NH, Sweeney DJ, Rapaport SI (1985) Inability of dimethyl sulfoxide to increase brain uptake of water-soluble compounds: Implications to chemotherapy for brain tumors. Cancer Treat Rep 69: 305–312PubMedGoogle Scholar
  96. 94.
    Groothuis DR, Molnar P, Blasberg RG (1984) Regional blood flow and blood-totissue transport in five brain tumor models. Prog Exp Tumor Res 27: 132 – 153PubMedGoogle Scholar
  97. 95.
    Haid M, Khandekar JD, Christ M, et al. (1985) Aziridinylbenzoquinone in recurrent, progressive glioma of the central nervous system. Cancer 56: 1311 – 1315PubMedGoogle Scholar
  98. 96.
    Hawkey CJ, Toghill PJ (1984) The need for prophylactic treatment to the central nervous system in patients with aggressive non-Hodgkin’s lymphoma. Postgrad Med J 59: 283 – 297Google Scholar
  99. 97.
    Henson RA, Urich H (1982) Cancer and the nervous system: the neurological manifestations of systemic malignant disease. Blackwell, LondonGoogle Scholar
  100. 98.
    Herbst KD, Corder MP, Justice GR (1976) Successful therapy with methotrexate of a multicentric mixed lymphoma of the central nervous system. Cancer 38: 1476 – 1478PubMedGoogle Scholar
  101. 99.
    Herchbergs A, Sahar A, Tadmor R, Brenner HJ (1985) Primary cerebral neoplasia—Rapid performance status improvement (upgrading) following hypofractionated radiation combined with cisplatinum. Proc Am Soc Clin Oncol 4: C 516Google Scholar
  102. 100.
    Hochberg FH, Parker LM, Takvorian T, Canellos GP, Zervas NT (1981) High-dose BCNU with autologous bone marrow rescue for recurrent glioblastoma multiforme. J Neurosurg 54: 455 – 460PubMedGoogle Scholar
  103. 101.
    Hoshino T, Wilson CB, Rosenblum, ML, Baker M (1975) Chemotherapeutic implications of growth fraction and cell cycle time in glioblastoma. J Neurosurg 43: 127 – 135PubMedGoogle Scholar
  104. 102.
    Hoshino T (1979) The cell kinetics of gliomas: its prognostic value and therapeutic implications. In: Paoletti P, Walker MD, Butti G, Knerich R (eds) Multidisciplinary aspects of brain tumor therapy. Elsevier/North-Holland, New York, pp 105 – 112Google Scholar
  105. 103.
    Hoshino T, Wilson CB (1979) Cell kinetic analyses of human malignant brain tumors (gliomas). Cancer 44: 956 – 962PubMedGoogle Scholar
  106. 104.
    Hoshino T, Kobayashi S, Townsend JJ, Wilson CB (1985) A cell kinetic study on medulloblastomas. Cancer 55: 1711 – 1713PubMedGoogle Scholar
  107. 105.
    Howell SB, Pfeifle CE, Wung WE, Olshen RA (1983) Intraperitoneal cisdiamminedichloroplatinum with systemic thiosulfate protection. Cancer Res 43: 1426–1431PubMedGoogle Scholar
  108. 106.
    Hrushesky WJM (1984) Chemotherapy timing: an important variable in toxicity and response. In: Perry MC, Yarboro JW (eds) Toxicity of chemotherapy. Grune and Stratton, New York, pp 449 – 477Google Scholar
  109. 107.
    Hu E, Howell SB (1984) Pharmacokinetics of intraarterial mitomycin C in humans. Cancer Res 43: 4474 – 4477Google Scholar
  110. 107.
    a. Hwang TL, Yung WKA, Estey EH, Fields WS (1985) Central nervous toxicity with leigh-dose Ara-C. Neurology 35: 1475 – 1479PubMedGoogle Scholar
  111. 108.
    Irwin L, George F, Pitts F (1975) Hydroxyurea and radiation therapy in primary intracranial malignant glial tumors. Proc Am Assoc Cancer Res 16: 243Google Scholar
  112. 109.
    Jackson RC, Harkrader RJ (1981) Synergistic and antagonistic interactions of methotrexate and 1–13-D-arabinofluranosyl-cytosine in hepatoma cells. Biochem Pharmacol 30: 223 – 229PubMedGoogle Scholar
  113. 110.
    Jay JR, MacLaughlin DT, Riley KR, Martuza RL (1985) Modulation of meningioma cell growth by sex steroid hormones in vitro. J Neurosurg 62: 757 – 762PubMedGoogle Scholar
  114. 111.
    Jellinger K (1983) Pathologic effects of chemotherapy. In: Walker MD (ed) Oncology of the nervous system. M Nijhoff, Boston, pp 285 – 340Google Scholar
  115. 112.
    Jellinger K (1985) Changes induced in anaplastic gliomas and brain tissue as a result of treatment. In: Voth D, Krauseneck P (eds) Chemotherapy of gliomas. De Gruyter, Berlin, pp 153 – 176Google Scholar
  116. 112.
    a. Johnson HA, Haymaker WE, Rubini JR, et al. (1960) A radioautographic study of a human and glioblastoma multiforme after the in vivo uptake of tritiated thymidine. Cancer 13: 636 – 642PubMedGoogle Scholar
  117. 113.
    Kantarjian H, Farah PAM, Spitzer G, Murphy WK, Valdivieso M (1984) Systemic combination chemotherapy as primary treatment of brain metastasis from lung cancer. Southern Med J 77: 426 – 430PubMedGoogle Scholar
  118. 114.
    Kaplan RS, Wiernick PH (1984) Neurotoxicity of antitumor agents. In: Perry MC, Yarbro JW (eds) Toxicity of chemotherapy. Grune and Stratton, New York, pp 365–431Google Scholar
  119. 115.
    Kessinger A (1984) High dose chemotherapy with autologous bone marrow rescue for high grade gliomas of the brain: a potential for improvement in therapeutic results. Neurosurgery 15: 747 – 750PubMedGoogle Scholar
  120. 116.
    Kirkwood JM, Ensminger W, Rosowsky A, et al. (1980) Comparison of pharmacokinetics of 5-fluorouracil and 5-fluorouracil with concurrent thymidine infusions in a phase I trial. Cancer Res 40: 107 – 113PubMedGoogle Scholar
  121. 117.
    Koenig H (1970) Biochemical basis for fluorouracil neurotoxicity: The role of Krebs cycle by inhibition by fluoroacetate. Arch Neurol 23: 155 – 160PubMedGoogle Scholar
  122. 118.
    Kuhn J, von Hoff DD, et al (1983) Phase I trial of 2-fluoro-ara-AMP (NSC 312887 ). Fourth NCI-EORTC symposium on new drugs in cancer therapy, BrusselsGoogle Scholar
  123. 119.
    Kumar ARV, Renaudin J, Wilson CB, et al. (1974) Procarbazine hydrochloride in the treatment of brain tumors. J Neurosurg 40: 365 – 371Google Scholar
  124. 120.
    Laerum OD, Bjerkvig R, Steinsvag SK, de Ridder L (1984) Invasiveness of primary brain tumors. Cancer Metastasis Rev 3: 223 – 236Google Scholar
  125. 121.
    Layton PB, Greenberg HS, Stetson PL, Ensminger WD, Gyves JW (1984) BCNU solubility and toxicity in the treatment of malignant astrocytomas. J Neurosurg 60: 1134 – 1137PubMedGoogle Scholar
  126. 122.
    Letendre L, Banks PM, Reese DF, et al. (1982) Primary lymphoma of the central nervous system. Cancer 49: 939 – 943PubMedGoogle Scholar
  127. 123.
    Levin VA, Wheeler KT (1982) Chemotherapeutic approaches to brain tumors: Experimental observations with dianhydrogalactitol and dibromodulcitol. Cancer Chemother Pharmacol 8: 125–131PubMedGoogle Scholar
  128. 124.
    Levin VA, Vestnys PS, Edwards MS, et al. (1983) Improvement in survival produced by sequential therapies in the treatment of recurrent medulloblastoma. Cancer 51: 1364–1370PubMedGoogle Scholar
  129. 125.
    Levin VA, Byrd D, Sikic BI, et al. (1985) Central nervous system toxicity and cerebrospinal fluid pharmacokinetics of intraventricularly administered bleomycin in beagles. Cancer Res 45: 3810 – 3815PubMedGoogle Scholar
  130. 126.
    Levin V, Choucair A, Davis RL, et al. (1985) Development of CNS “metastases” in patients with glioblastoma multiforme and other anaplastic gliomas while undergoing therapy. Sixth international conference on brain tumor research and therapy, Asheville (abstract)Google Scholar
  131. 127.
    Lieberman A, le Brun Y, Glass P, et al. (1977) Use of high dose corticosteroids in patients with inoperable brain tumours. J Neurol Neurosurg Psychiat 40: 678–682PubMedGoogle Scholar
  132. 128.
    Loeffler JS, Ervin TJ, Mauch P, et al. (1985) Primary lymphomas of the central nervous system: Patterns of failure and factors that influence survival. J. Clin Oncol 3: 490–494PubMedGoogle Scholar
  133. 129.
    Loehrer PJ, Einhorn LH (1984) Cisplatin. Ann Intern Med 100: 704–713Google Scholar
  134. 130.
    Logothetis CJ, Samuels ML, Trindade A (1982) The management of brain metastases in germ cell tumors. Cancer 49: 12 – 18PubMedGoogle Scholar
  135. 131.
    Long DM, Hartmann FJ, French LA (1969) The response of human cerebral edema to glucosteroid administration—An electron microscopic study. Neurology 31: 521 – 528Google Scholar
  136. 132.
    Mackintosh FR, Colby TV, Podolsky WJ, et al. (1982) Central nervous system involvement in non-Hodgkin’s lymphoma: an analysis of 105 cases. Cancer 49: 586–595PubMedGoogle Scholar
  137. 133.
    Maeda H, Sano Y, Takeshita J. et al. (1981) A pharmacokinetic simulation model for chemotherapy of brain tumor with an antitumor protein antibiotic, neocarzinostatin: theoretical considerations behind a two-compartment model for continuous infusion via an internal carotid artery. Cancer Chemother Pharmacol 5: 243 – 249PubMedGoogle Scholar
  138. 134.
    Mahaley MS (1985) Summary of clinical trials of chemotherapy and conventional radiation therapy in the treatment of patients with primary malignant brain tumors. Sixth international conference on brain tumor research and therapy, Asheville (abstract)Google Scholar
  139. 135.
    Mark VH, Kjellberg RN, Ojemann RG, Slolway AH (1960) Treatment of malignant brain tumors with alkylating agents. Neurology 10: 772 – 776PubMedGoogle Scholar
  140. 136.
    Markman M, Cleary S, Howell SB (1985) Nephrotoxicity of high-dose intracavitary cisplatin with intravenous thiosulfate protection. Eur J Cancer Clin Oncol 21: 1015–1018Google Scholar
  141. 137.
    Martin DS, Stolfi RL, Sawyer RC, Spiegelman S, Young CW (1983) Improved therapeutic index with sequential N-phosphonacetyl-L-aspartate plus high-doseGoogle Scholar
  142. methotrexate plus high-dose 5-fluorouracil and appropriate rescue. Cancer Res 43: 4653–4661Google Scholar
  143. 138.
    Matsuno H (1981) Tumor angiogenesis factor (TAF) in cultured cells derived from central nervous system tumors in humans. Neurol Med Chir 21: 765 – 773Google Scholar
  144. 139.
    Mealey J, Chen TT, Pedlow E (1970) Brain tumor chemotherapy with mithramycin and vincristine. Cancer 26: 260 – 367Google Scholar
  145. 139.
    a. Melgaard B, Hansen HS, Kamieniecka Z, Paulson OB, Pedersen AG, Tang X, Trojaborg W (1981) Misonidazole neuropathy: A clinical electrophysiological and histological study. Ann Neurol 12: 10–17Google Scholar
  146. 140.
    Mellett LB (1977) Physicochemical considerations and pharmacokinetic behavior in delivery of drugs to the central nervous system. Cancer Treat Rep 61: 527 – 531PubMedGoogle Scholar
  147. 141.
    Mendenhall NP, Thar TL, Agee OF, et al. (1983) Primary lymphoma of the central nervous system. Cancer 52: 1993 – 2000PubMedGoogle Scholar
  148. 142.
    Mooney C, Thomas DGT, Souhami RL (1983) Adriamycin in the treatment of relapsed primary malignant brain tumors. Eur J Cancer Clin Oncol 19: 1037 – 1038PubMedGoogle Scholar
  149. 143.
    Moran RG, Danenberg PV, Heidelberger C (1982) Therapeutic response of leukemic mice treated with fluorinated pyrimidines and inhibitors of deoxyuridylate synthesis. Biochem Pharmacol 31: 2929 – 2935PubMedGoogle Scholar
  150. 144.
    Morantz RA, Kimler BF, Vats TS, Henderson SD (1983) Bleomycin and brain tumors. J Neuro-Oncol 1: 249 – 255Google Scholar
  151. 145.
    Naysmith A, Robson RH (1979) Focal fits during chlorambucil therapy. Postgrad Med J 55: 806PubMedGoogle Scholar
  152. 146.
    Nelson JS, Tsukada Y, Schoenfeld D, et al. (1983) Necrosis as a prognostic criterion in malignant supratentorial, astrocytic gliomas. Cancer 52: 550 – 554PubMedGoogle Scholar
  153. 147.
    Neuwelt EA, Diehl JT, Hill SA, Marvilla KR (1979) Use of metrizamide computerized tomographic cisternography in the evaluation of patients with malignant glioma for immunotherapy. Neurosurgery 5: 576 – 582PubMedGoogle Scholar
  154. 148.
    Neuwelt EA, Frenkel EP, Diehl J, et al. (1980) Reversible osmotic blood-brain barrier disruption in humans: Implications for the chemotherapy of malignant brain tumors. Neurosurgery 7: 44–52PubMedGoogle Scholar
  155. 149.
    Neuwelt EA, Frenkel EP, Rapaport S, Barnett P (1980) Effect of osmotic blood-brain barrier disruption on methotrexate pharmacokinetics in the dog. Neurosurgery 7: 3643Google Scholar
  156. 150.
    Neuwelt EA, Glasberg M, Diehl J, Frenkel EP, Barnett P (1981) Osmotic blood-brain barrier disruption in the posterior fossa of the dog. J Neurosurg 55: 742 – 748PubMedGoogle Scholar
  157. 151.
    Neuwelt EA, Pagel M, Barnett P, Glasberg M, Frenkel EP (1981) Pharmacology and toxicity of intracarotid adriamycin administration following osmotic blood-brain barrier modification. Cancer Res 41: 4466 – 4470PubMedGoogle Scholar
  158. 152.
    Neuwelt EA, Frenkel EP (1982) Osmotic blood-brain barrier disruption as a means of increasing chemotherapeutic agent delivery to the central nervous system: animal and clinical studies. In: Hildegrand J, Gangji D (eds) Treatment of neoplastic lesions of the nervous system. Pergamon Press, New York, pp 129 – 133Google Scholar
  159. 153.
    Neuwelt EA, Balaban E, Diehl J, Hill S, Frenkel E (1983) Successful treatment of primary central nervous system lymphomas with chemotherapy after osmotic blood-brain barrier opening. Neurosurgery 12: 662 – 671PubMedGoogle Scholar
  160. 154.
    Neuwelt EA, Barnett PA, Glasberg M, Frenkel EP (1983) Pharmacology and neurotoxicity of cis-diamminedichloroplatinum, bleomycin, 5-fluorouracil, and cyclophosphamide administration following osmotic blood-bran barrier modification. Cancer Res 43: 5278 – 5285PubMedGoogle Scholar
  161. 155.
    Neuwelt EA, Glasberg M, Frenkel E, Barnett P (1983) Neurotoxicity of chemotherapeutic agents after blood-brain barrier modification: Neuropathological studies. Ann Neurol 14: 316–324PubMedGoogle Scholar
  162. 156.
    Neuwelt EA, Specht HD, Howieson J, et al. (1983) Osmotic blood-brain barrier modification: Clinical documentation by enhanced CT scanning and/or radionuclide brain scanning. AJNR 4: 907–913Google Scholar
  163. 157.
    Neuwelt EA (1984) Therapeutic potential for blood-brain barrier modification in malignant brain tumors. Prog Exp Tumor Res 28: 51 – 66PubMedGoogle Scholar
  164. 158.
    Neuwelt EA, Barnett PA, Frenkel EP (1984) Chemotherapeutic agent permeability to normal brain and delivery to avian sarcoma virus-induced brain tumors in the rodent: Observations on problems of drug delivery. Neurosurgery 14: 154–160PubMedGoogle Scholar
  165. 159.
    Neuwelt EA, Barnett PA, McCormick CI, Frankel EP (1984) Osmotic blood-brain barrier modification: Parameters effecting drug delivery. In: Caciagli F, Giacobini E, Paoletti R (eds) Developmental neuroscience: physiological, pharmacological and clinical aspects. Elsevier, New York, pp 173 – 179Google Scholar
  166. 160.
    Neuwelt EA, Frenkel EP (1984) Germinomas and other pineal tumors: chemotherapeutic responses. In: Neuwelt EA (ed) Diagnosis and treatment of pineal region tumors. Williams and Wilkins, Baltimore, pp 332 – 343Google Scholar
  167. 161.
    Neuwelt EA, Hill SA, Frenkel EP (1984) Osmotic blood-brain barrier modification and combination chemotherapy: concurrent tumor regression in areas of barrier opening and progression in brain regions distant to barrier opening. Neurosurgery 15: 362 – 366PubMedGoogle Scholar
  168. 162.
    Neuwelt EA, Rapaport SI (1984) Modification of the blood-brain barrier in the chemotherapy of malignant brain tumors. Fed Proc 43: 214 – 219PubMedGoogle Scholar
  169. 163.
    Neuwelt EA, Barnett PA, McCormick CI, Frenkel EP, Minna JD (1985) Osmotic blood-brain barrier modification: Monoclonal antibody, albumin, and methotrexate delivery to cerebrospinal fluid and brain. Neurosurgery 17: 419–423PubMedGoogle Scholar
  170. 164.
    Neuwelt EA, Frenkel EP, d’Agostino AN, et al. (1985) Growth of human lung tumor in the brain of the nude rat as a model to evaluate antitumor agent delivery across the blood-brain barrier. Cancer Res 45: 2827 – 2833PubMedGoogle Scholar
  171. 165.
    Neuwelt EA, Frenkel EP, Gumerlock MK, et al. (1986) Developments in the diagnosis and treatment of primary CNS lymphoma: A prospective series. Cancer 58: 1609–1620PubMedGoogle Scholar
  172. 166.
    Neuwelt EA, Specht HD, Hill SA (1986) Permeability of human brain tumor to 99mTcglucoheptonate and 99mTc-albumin: Implications for monoclonal antibody therapy. J Neurosurg 65: 194–198Google Scholar
  173. 170.
    Neuwelt EA, Hill SA (1986) Chemotherapy administered in conjunction with osmotic blood-brain barrier modification in patients with brain metastases. J Neurooncol (in press)Google Scholar
  174. 167.
    Neuwelt EA, Howieson J, Frenkel EP, Specht D, Weigel R, et al. (1986) Therapeutic efficacy of multiagent chemotherapy with drug delivery enhancement by blood-barrier modification in glioblastoma. Neurosurgery 19: 573 – 582PubMedGoogle Scholar
  175. 168.
    Neuwelt EA, Minna J, Frenkel E, Barnett PA, McCormick CI (1986) Osmotic blood-brain barrier opening to IgM monoclonal antibody in the rat. Am J Physiol 250: R 875—R 883Google Scholar
  176. 169.
    Neuwelt EA, Specht HD, Hill SA (1986) Permeability of human brain tumor to 99mTcglucoheptonate and 99mTc-albumin: Implications for monoclonal antibody therapy. J Neurosurg 65: 194–198PubMedGoogle Scholar
  177. 170.
    O’Dwyer PJ, Leyland-Jones B, Alonso MT, Marsoni S, Wittes RE (1985) Etoposide (VP-16–213): Current status of an active anticancer drug. New Engl J Med 312: 692–700PubMedGoogle Scholar
  178. 171.
    Ogawa M (1981) Current status of nitrosoureas under development in Japan. In: Prestayko AW, et al. (eds) Nitrosoureas: current status and new developments. Academic Press, New York, pp 399 – 410Google Scholar
  179. 172.
    Oldfield EH, Dedrick RL, Chatterji DC, et al. (1985) Arterial drug infusion with extracorporeal removal. II. Internal carotid carmustine in the rhesus monkey. Cancer Treat Rep 69: 293–303PubMedGoogle Scholar
  180. 173.
    Oster MW (1979) Combination chemotherapy for extracranial metastases of a primary malignant cerebral neoplasms. Cancer Treat Rep 63: 1417 – 1418PubMedGoogle Scholar
  181. 174.
    Owens G (1969) Intraarterial chemotherapy of primary brain tumors. Ann NY Academy Sci 159: 603 – 607Google Scholar
  182. 175.
    Poplack DG, Bleyer WA, Horowitz ME (1980) Pharmacology of antineoplastic agents in cerebrospinal fluid. In: Wood JH (ed) Neurobiology of cerebrospinal fluid I. Plenum Press, New York, pp 561 – 578Google Scholar
  183. 176.
    Posner JB, Howieson J, Cvitkovic E (1977) “Disappearing” spinal cord compression: Oncolytic effect of glucocorticoids (and other chemotherapeutic agents) on epidural metastases. Ann Neurol 2: 409–413PubMedGoogle Scholar
  184. 177.
    Postmus PE, Holthius JJM, Haaxma-Reiche G, et al. (1984) Penetration of VP 16–213 into cerebrospinal fluid after high-dose intravenous administration. J Clin Oncol 2: 215 – 220PubMedGoogle Scholar
  185. 178.
    Rapoport SI (1976) Blood-brain barrier in physiology and medicine. Raven Press, New YorkGoogle Scholar
  186. 179.
    Riccardi R, Bleyer WA, Poplack DG (1983) Enhancement of delivery of antineoplastic drugs into cerebrospinal fluid. In: Wood JH (ed) Neurobiology of cerebrospinal fluid II. Plenum Press, New York, pp 453 – 466Google Scholar
  187. 180.
    Rose C, Mouridsen HT (1984) Treatment of advanced breast cancer with tamoxifen. Recent Results Cancer Res 91: 230 – 242PubMedGoogle Scholar
  188. 181.
    Rosner D, Nemoto T, Pickren J, Lane W (1983) Management of brain metastases from breast cancer by combination chemotherapy. J Neuro-Oncol 1: 131 – 137Google Scholar
  189. 182.
    Ross RL, Kapp JP, Hochberg F, et al. (1983) Solvent systems for intracarotid 1,3-Bis(2-chloroethyl)-1-nitrosourea ( BCNU) infusion. Neurosurgery 12: 512–514PubMedGoogle Scholar
  190. 183.
    Rozenthal J, Trump D, Finlay J, et al. (1985) Pilot study of eight-drugs-in-one-day chemotherapy for high-grade astrocytomas. Sixth international conference on brain tumor research and therapy, Asheville (abstract)Google Scholar
  191. 184.
    Russo A, Gianni L, Kinsella TJ, et al. (1984) Pharmacological evaluation of intravenous delivery of 5-bromodeoxyuridine to patients with brain tumors. Cancer Res 44: 1702 – 1705PubMedGoogle Scholar
  192. 185.
    Schabel FM, Griswold DP, Corbett TH, Laster WR (1984) Increasing the therapeutic response rates to anticancer drugs by applying the basic principles of pharmacology. Cancer 54: 1160 – 1167PubMedGoogle Scholar
  193. 186.
    Schilsky RL, Yarbro JW (1984) Pharmacology of antineoplastic drugs. In: Perry MC, Yarbro JW (eds) Toxicity of chemotherapy. Grune and Stratton, New York, pp 21 – 59Google Scholar
  194. 187.
    Schnur G, Choy M, Stirling M, et al. (1984) Hemodynamic consequences of combined 188. Schold SC, Carincross JG, Bullard DE (1984) Chemotherapy of primary brain tumors. In: Wilkins RH, Rengachary S (eds) Neurosurgery. McGraw-Hill, New York, pp 1143 – 1153Google Scholar
  195. 189.
    Schold SC, Friedman HS, Bjornsson TD, Falletta JM (1984) Treatment of patients with recurrent primary brain tumors with AZQ. Neurology 34: 615 – 619PubMedGoogle Scholar
  196. 190.
    Schroff RW, Foon KA, Beatty SM, Oldham RK, Morgan AC (1985) Human antimurine immunoglobulin responses in patients receiving monoclonal antibody therapy. Cancer Res 45: 879 – 885PubMedGoogle Scholar
  197. 191.
    Sexauer C, Kahn A, Burger P, et al. (1984) Cisplatinum in recurrent pediatric brain tumors: A phase II study. Proc Am Soc Clin Oncol 3: 329Google Scholar
  198. 192.
    Shapiro WR, Byrne TN (1983) Chemotherapy of brain tumors Basic concepts. In: Walker MD (ed) Oncology of the nervous system. M Nijhoff, Boston, pp 65 – 100Google Scholar
  199. 193.
    Shapiro WR (1985) Cell biology of primary brain tumors. Paper presented at the meeting of the American Academy of Neurology, DallasGoogle Scholar
  200. 194.
    Shoemaker DD, O’Dwyer PJ, Marsoni S, et al. (1983) Spiromustine: a new agent entering clinical trials. Invest New Drugs 1: 303 – 308PubMedGoogle Scholar
  201. 195.
    Siegal T, Pfeffer MR, Catane R, et al. (1983) Successful chemotherapy of recurrent intracranial germinoma with spinal metastases. Neurology 33: 631 – 636PubMedGoogle Scholar
  202. 196.
    Sirotnak FM, Moccio DM, Hancock CH, et al. (1981) Improved methotrexate therapy of murine tumors obtained by probenecid-mediated pharmacological modulation of the level of membrane transport. Cancer Res 41: 3944 – 3949PubMedGoogle Scholar
  203. 197.
    Skarin AT, Zukerman KS, Pitman SW, et al. (1977) High-dose methotrexate with folinic acid in the treatment of advanced non-Hodgkin lymphoma including CNS involvement. Blood 50: 1039 – 1947PubMedGoogle Scholar
  204. 198.
    Slyter H, Liwnicz B, Herrick MK, et al. (1980) Fatal myeloencephalopathy caused by intrathecal vincristine. Neurology 30: 867 – 871PubMedGoogle Scholar
  205. 199.
    Spector R, Eells J (1984) Deoxynucleoside and vitamin transport into the central nervous system. Fed Proc 43: 196 – 200PubMedGoogle Scholar
  206. 200.
    Spigelman MK, Zappulla RA, Goldberg JD, et al. (1984) Effect of intracarotid etoposide on opening the blood-brain barrier. Cancer Drug Delivery 1: 207 – 211PubMedGoogle Scholar
  207. 201.
    Spigelman MK, Zappulla RA, Johnson J, et al. (1984) Etoposide-induced blood-brain barrier disruption. J Neurosurg 61: 674 – 678PubMedGoogle Scholar
  208. 202.
    Stewart DJ, Leavens M, Maor M, et al. (1982) Human central nervous system distribution of cis-diamminedichloroplatinum and use as a radiosensitizer in malignant brain tumors. Cancer Res 42: 2474 – 2479PubMedGoogle Scholar
  209. 203.
    Stewart DJ, Hugenholtz RH, Dennery J (1984) VP-16 (VP) and VM-26 (VM) penetration into human brain tumors ( BT ). Proc Am Assoc Cancer Res 24: 527Google Scholar
  210. 204.
    Stewart DJ, Russel N, Atack EA, Quarrington A, Stolbach L (1983) Cyclophosphamide, doxorubicin, vincristine, and dexamethasone in primary lymphoma of the brain: A case report. Cancer Treat Rep 67: 287–291PubMedGoogle Scholar
  211. 205.
    Stewart DJ (1984) Novel modes of chemotherapy administration. Prog Exp Tumor Res 28: 32 – 50PubMedGoogle Scholar
  212. 206.
    Stewart DJ, Grahovak Z, Benoit B, et al. (1984) Intracarotid chemotherapy with a combination of 1,3-bis(2-chlorethyl)-1-nitrosourea (BCNU), cis-diaminedichloroplatinum (Cisplatin), and 4’-O-demethyl-1-O-(4,6-O-2-thenylidene-13-D- glucopyranosyl) epipodophyllotoxin (VM-26) in the treatment of primary and metastatic brain tumors. Neurosurgery 15: 828 – 833PubMedGoogle Scholar
  213. 207.
    Stewart DJ, Russell N, Atack EA, Quarrington A, Stolback L (1984) Cyclophosphamide, doxorubicin, vincristine, and dexamethasone in the treatment of bulky CNS lymphoma. J Neuro-Oncol 2: 289Google Scholar
  214. 208.
    Stewart DJ, Grahovaz Z, Maroun J, et al. (1985) Intraarterial (IA) chemotherapy (CT) for brain tumors (BT). Proc Am Soc Clin Oncol 4: C 513Google Scholar
  215. 209.
    Sullivan KM, Storb R, Shulman HM, et al. (1982) Immediate and delayed neurotoxicity after mechlorethamine preparation for bone marrow transplantation. Ann Int Med 98: 182 – 189Google Scholar
  216. 210.
    Syndran AC (1981) The cytosine arabinoside (Ara-C) syndrome. Med Ped Oncol 9: 257 – 264Google Scholar
  217. 211.
    Takahashi H, Nakazawa S, Shimura T (1985) Evaluation of postoperative intra-tumoral injection of bleomycin for craniopharyngioma in children. J Neurosurg 62: 120 – 127PubMedGoogle Scholar
  218. 212.
    Takakura K, Sano K, Hojo S, Hirano A (1982) Metastatic tumors of the central nervous system. Igaku-Shoin, Tokyo New YorkGoogle Scholar
  219. 213.
    Thompson SW, Davis LE, Kornfeld M, Hilgers RD, Standefer JC (1984) Cisplatin neuropathy: Clinical, electrophysiologic, morphologic and toxicologic studies. Cancer 54: 1269–1275PubMedGoogle Scholar
  220. 214.
    Tirelli U, d’Incalci M, Canetta R, et al. (1984) Etoposide (VP-16–213) in malignant brain tumors: A phase II study. J Clin Oncol 2: 432–437PubMedGoogle Scholar
  221. 215.
    Tsuruo T, Iida H, Tsukagoshi S, et al. (1981) Overcoming of vincristine resistance in P 388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res 41: 1967 – 1972PubMedGoogle Scholar
  222. 216.
    Ushio Y (1985) Intrathecal ACNU against leptomeningeal dissemination of tumor: experimental study. Sixth international conference on brain tumor research and therapy, Asheville (abstract)Google Scholar
  223. 217.
    Vermorken JB, Stam J, Karim AB, etal. (1983) Treatment of small cell lung cancer ( SCLC) utilizing two alternating combination chemotherapy regimens. Proc Am Soc Clin Oncol 2: 785Google Scholar
  224. 218.
    Vole D, Jellinger K, Grisold W, et al. (1985) Combined radiation and polychemotherapy (COMP) in the postoperative treatment of high-grade supratentorial gliomas. In: Voth D, Krauseneck P (eds) Chemotherapy of gliomas. De Gruyter, Berlin, pp 341 – 352Google Scholar
  225. 219.
    Von Hoff DD, Reichert CM, Cuneo R, et al. (1979) Demyelinization of peripheral nerves associated with cis-diamminedichloroplatinum (II) ( DDP) therapy. Proc Am Assoc Cancer Res 20: 367Google Scholar
  226. 220.
    Wahl RL, Parker CW, Philpott GW (1983) Improved radioimaging and tumor localization with monoclonal F(ab’). J Nuc Med 24: 316 – 325Google Scholar
  227. 221.
    Walker MD, Weiss HD (1975) Chemotherapy in the treatment of malignant brain tumors. Adv Neurol 13: 149–191PubMedGoogle Scholar
  228. 222.
    Walker MD, Green SB, Byar DP, etal. (1980) Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glionta after surgery. New Engl J Med 303: 1323 – 1329PubMedGoogle Scholar
  229. 223.
    Warnke P, Groothuis D, Kuruvilla A, et al. (1985) The effect of corticosteroids on drug delivery parameters in experimental brain tumors. Sixth international conference on brain tumor research and therapy, Asheville (abstract)Google Scholar
  230. 224.
    Wasserman TH, Stetz J, Phillips TL (1981) Radiation therapy oncology group clinical trials with misonidazole. Cancer 47: 2382 – 2390PubMedGoogle Scholar
  231. 225.
    Weiss HD, Walker MD, Wiernik PH (1974) Neurotoxicity of commonly used antineoplastic agents (parts I and II). New Engl J Med 291: 75 – 81PubMedGoogle Scholar
  232. 226.
    Weiss HD, Wiernick PH, Walker MD (1974) Intrathecal N, N’, N“-Triethylenethiophosphoramide [Thio-TEPA (NSC 6396)] in the treatment of malignant meningeal disease phase I—II study. Proc Am Assoc Cancer Res 15: 257Google Scholar
  233. 227.
    Weissman D, Grossman S (1985) Temporal development of peritumoral brain edema in rabbit VX 2 brain tumors. Sixth international conference on brain tumor research and therapy, Asheville (abstract)Google Scholar
  234. 228.
    West CR, Avellanosa AM, Barua NR, Patel A, Hong CI (1983) Intra-arterial 1,3-Bis(2chlorethyl)-1-nitrosourea (BCNU) and systemic chemotherapy for malignant gliomas: A follow-up study. Neurosurgery 13: 420–426PubMedGoogle Scholar
  235. 229.
    White JC, Fernandes DJ, Capizzi RL (1984) Pharmacologic approaches to combination chemotherapy. In: Perry MC, Yarbro JW (eds) Toxicity of chemotherapy. Grune and Stratton, New York, pp 61 – 99Google Scholar
  236. 230.
    Williams ME, Walker AN, Bracikowski JP, et al. (1983) Ascending myeloencephalopathy due to intrathecal vincristine sulfate: a fatal chemotherapeutic error. Cancer 51: 2041 – 2047PubMedGoogle Scholar
  237. 231.
    Williams SA, etal (1978) Seizures: significant side effect of chlorambucil therapy in children. J Peds 93: 516–518Google Scholar
  238. 232.
    Wilson CB, Levin V, Hoshino T (1982) Chemotherapy of brain tumors. In: Youmans JR (ed) Neurological surgery. W B Saunders, Philadelphia, pp 3065 – 3095Google Scholar
  239. 233.
    Yalowich JC, Fry DW, Goldman ID (1982) Teniposide (VM-26) and etoposide (VP- 16–2132)-induced augmentation of methotrexate transport and polyglutamylation in Ehrlich ascites tumor cells in vitro. Cancer Res 42: 3648 – 3653PubMedGoogle Scholar
  240. 234.
    Yamashita J, Handa H, Tokuriki Y, et al. (1984) Intra-arterial ACNU therapy for malignant brain tumors. J Neurosurg 59: 424 – 430Google Scholar
  241. 235.
    Young DF, Posner JB (1980) Nervous system toxicity of the chemotherapeutic agents. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology. North-Holland, New York, pp 91 – 129Google Scholar
  242. 236.
    Zager RF, Frisby SA, Oliverio VT (1973) The effects of antibiotics and cancer chemotherapeutic agents on the cellular transport and antitumor activity of methotrexate in L 1210 murine leukemia. Cancer Res 33: 1670 – 1676PubMedGoogle Scholar
  243. 237.
    Zimm S, Collins JM, Curt GA, O’Neill D, Poplack DG (1984) Cerebrospinal fluid pharmacokinetic of intraventricular and intravenous aziridinylbenozquinone. Cancer Res 44: 1698 – 1701PubMedGoogle Scholar

Copyright information

© Springer-Verlag/Wien 1987

Authors and Affiliations

  • Mary K. Gumerlock
    • 1
  • E. A. Neuwelt
    • 1
  1. 1.Department of NeurosurgeryThe Oregon Health Sciences UniversityPortlandUSA

Personalised recommendations