CNS Drugs

, Volume 15, Issue 9, pp 719–743 | Cite as

Pharmacotherapy of Malignant Astrocytomas of Children and Adults

Current Strategies and Future Trends
  • Mark T. Jennings
  • Sunita Iyengar
Review Article

Abstract

This article reviews the conceptual progression in the pharmacological therapy of malignant astrocytoma (MA) over the past decade, and its future trends. It is a selective rather than an exhaustive inventory of literature citations. The experience of the Brain Tumour Cooperative Group (BTCG) and earlier phase III trials are summarised to place subsequent phase II and I studies of single and combination agent chemotherapy in perspective.

The BTCG experience of the 1970s to 1980s may be summarised to indicate that external beam radiotherapy (EBRT) is therapeutic, although not curative, and not further improved upon by altering fractionation schedules, or the addition of radioenhancers. Whole brain and reduced whole brain EBRT with focal boost were comparable regimens. Nitrosourea-based, adjuvant chemotherapy provided a modest improvement in survival among adult patients, which was comparable with that of other single drugs or multidrug regimes. The multiagent schedules, however, had a correspondingly higher toxicity rate. Intra-arterial administration was associated with significant risk, which conferred no therapeutic advantage.

The trend of the past decade has been towards multiagent chemotherapy although its benefit cannot be predicted from the classic prognostic factors. Published experience with investigational trials utilising myeloablative chemotherapy with autologous bone marrow or peripheral blood stem cell haemopoietic support, drug delivery enhancement methods and radiosensitisers is critically reviewed. None of these approaches have achieved wide-spread acceptance in the treatment of adult patients with MA. Greater attention is placed on recent ‘chemoradiotherapy’trials, which attempt to integrate and maximise the cytoreductive potential of both modalities. This approach holds promise as an effective means to delay or overcome the evolution of tumour resistance, which is probably one of the dominant determinants of prognosis. However, the efficacy of this approach remains unproven. New chemotherapeutic agents as well as biological response modifiers, protein kinase inhibitors, angiogenesis inhibitors and gene therapy are also discussed; their role in the therapeutic armamentarium has not been defined.

Keywords

External Beam Radiation Therapy Topotecan Anaplastic Astrocytoma Peripheral Blood Stem Cell Carmustine 

Notes

Acknowledgements

This work was supported by the S.C. Montgomery and M.D. Greene Research Funds.

References

  1. 1.
    Shapiro WR. Treatment of neuroectodermal brain tumors. Ann Neurol 1982; 12: 231–7PubMedCrossRefGoogle Scholar
  2. 2.
    Shapiro WR. Therapy of adult malignant brain tumors: what have the clinical trials taught us? Semin Oncol 1986; 13: 38–45PubMedGoogle Scholar
  3. 3.
    Shapiro WR, Green SB, Burger PC, et al. Randomized trial of three chemotherapy regimens and two radiotherapy regimens in postoperative treatment of malignant glioma. Brain Tumor Cooperative Group Trial 8001. J Neurosurg 1989; 71: 1–9Google Scholar
  4. 4.
    Shapiro WR, Green SB, Burger PC, et al. A randomized comparison of intra-arterial vs intravenous BCNU, with or without intravenous 5-fluorouracil, for newly diagnosed patients with malignant glioma. J Neurosurg 1992; 76: 772–81PubMedCrossRefGoogle Scholar
  5. 5.
    Hiesiger EM, Green SB, Shapiro WR, et al. Results of a randomized trial comparing intra-arterial cisplatin and intravenous PCNU for the treatment of primary brain tumors in adults. Brain Tumor Cooperative Group Trial 8420-A. J Neurooncol 1995; 25: 143–54Google Scholar
  6. 6.
    Fine HA, Dear KB, Loeffler JS, et al. Meta-analysis of radiation therapy with or without adjuvant chemotherapy for malignant gliomas in adults. Cancer 1993; 71: 2585–97PubMedCrossRefGoogle Scholar
  7. 7.
    Sposto R, Ertel IJ, Jenkin RDT, et al. The effectiveness of chemotherapy for treatment of high grade astrocytoma in children: results of a randomized trial. J Neurooncol 1989; 7: 165–77PubMedCrossRefGoogle Scholar
  8. 8.
    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 1980; 64: 1179–1205PubMedGoogle Scholar
  9. 9.
    Brandes AA, Fiorentino MV. The role of chemotherapy in recurrent malignant gliomas: an overview. Cancer Invest 1996; 14: 551–6PubMedCrossRefGoogle Scholar
  10. 10.
    Allen JC, Helson L. High-dose cyclophosphamide chemotherapy for recurrent CNS tumors in children. J Neurosurg 1981; 55: 749–56PubMedCrossRefGoogle Scholar
  11. 11.
    Phuphanich S, Edwards MS, Levin VA, et al. Supratentorial malignant gliomas of childhood: results of treatment with radiation therapy and chemotherapy. J Neurosurg 1984; 60: 495–9PubMedCrossRefGoogle Scholar
  12. 12.
    Hancock C, Allen J, Tan C. Phase II trial of PCNU in children with recurrent brain tumors and Hodgkins disease. Cancer Treat Rep 1984; 68: 441–2PubMedGoogle Scholar
  13. 13.
    Allen JC, Hancock C, Walker R, et al. PCNU and recurrent childhood brain tumors. J Neurooncol 1987; 5: 241–4PubMedCrossRefGoogle Scholar
  14. 14.
    Walker RW, Allen JC. Treatment of recurrent primary intracranial childhood tumors with cis-diaminedichloroplatinum. Ann Neurol 1983; 14:371–2Google Scholar
  15. 15.
    Sexauer CL, Khan A, Burger PC, et al. Cisplatin in recurrent pediatric brain tumors: a POG phase II study. Cancer 1985; 56: 1497–501PubMedCrossRefGoogle Scholar
  16. 16.
    Diez B, Monges J, Sackmann-Muriel F. Evaluation of cisplatin in children with recurrent brain tumors. Cancer Treat Rep 1985; 69: 911–3PubMedGoogle Scholar
  17. 17.
    Walker RW, Allen JC. Cisplatin in the treatment of recurrent childhood primary brain tumors. J Clin Oncol 1988; 6: 62–6PubMedGoogle Scholar
  18. 18.
    Walker RW, Allen JC, Bacha D, et al. Treatment of recurrent primary brain tumors of childhood with carboplatin [abstract]. Ann Neurol 1985; 18: 406Google Scholar
  19. 19.
    Allen JC, Walker R, Luks E, et al. Carboplatin and recurrent childhood brain tumors. J Clin Oncol 1987; 5: 459–63PubMedGoogle Scholar
  20. 20.
    Gaynon PS, Ettinger LJ, Baum ES, et al. Carboplatin in childhood brain tumors: a Children’s Cancer Study Group phase II trial. Cancer 1990; 66: 2465–9PubMedCrossRefGoogle Scholar
  21. 21.
    Yung WK, Mechtler L, Gleason MJ. Intravenous carboplatin for recurrent malignant gliomas: a phase II study. J Clin Oncol 1991; 9: 860–4PubMedGoogle Scholar
  22. 22.
    Friedman HS, Krischer JF, Burger PC, et al. Treatment of children with progressive or recurrent brain tumors with carboplatin or iproplatin: a Pediatric Oncology Group randomized phase II study. J Clin Oncol 1992; 10: 249–56PubMedGoogle Scholar
  23. 23.
    Friedman HS, Lovell S, Rasheed K, et al. Treatment of adults with progressive oligodendroglioma with carboplatin (CBDCA): preliminary results. Med Pediatr Oncol 1998; 31: 16–8PubMedCrossRefGoogle Scholar
  24. 24.
    Levin VA, Edwards MS, Gutin PH, et al. Phase II evaluation of dibromodulcitol in the treatment of recurrent medulloblastoma, ependymoma and malignant astrocytoma. J Neurosurg 1984; 61: 1063–8PubMedCrossRefGoogle Scholar
  25. 25.
    Allen JC, Walker R, Rosen G. Preradiation high-dose intravenous methotrexate with leucovorin rescue for untreated primary childhood brain tumors. J Clin Oncol 1988; 6: 649–53PubMedGoogle Scholar
  26. 26.
    Chamberlain MC, Prados MD, Silver P, et al. Aphase I/II study of 24 hour intravenous AZQ in recurrent primary brain tumors. J Neurooncol 1988; 6: 319–23PubMedCrossRefGoogle Scholar
  27. 27.
    Ettinger LJ, Ru N, Krailo M, et al. A phase II study of diaziquone in children with recurrent or progressive primary brain tumors: a report of the Childrens Cancer Study Group. J Neurooncol 1990; 9: 69–76PubMedCrossRefGoogle Scholar
  28. 28.
    Heideman RL, Packer RJ, Reaman GH, et al. A phase II evaluation of thiotepa in pediatric central nervous system malignancies. Cancer 1993; 72: 271–5PubMedCrossRefGoogle Scholar
  29. 29.
    Chamberlain MC. Recurrent brainstem gliomas treated with oral VP-16. J Neurooncol 1993; 15: 133–9PubMedCrossRefGoogle Scholar
  30. 30.
    Kobrinsky NL, Packer RJ, Boyett JM, et al. Etoposide with or without mannitol for the treatment of recurrent or primarily unresponsive brain tumors: a Childrens Cancer Group Study, CCG- 9881. J Neurooncol 1999; 45: 47–54PubMedCrossRefGoogle Scholar
  31. 31.
    Abrahamsen TG, Lange BJ, Packer RJ, et al. Aphase I and II trial of dose-intensified cyclophosphamide and GM-cSF in pediatric malignant brain tumors. J Pediatr Hematol Oncol 1995; 17: 134–9PubMedCrossRefGoogle Scholar
  32. 32.
    Fetell MR, Grossman SA, Fisher JD, et al. New approaches to Brain Tumor Therapy Central Nervous System Consortium. Preirradiation paclitaxel in glioblastoma multiforme: efficacy, pharmacology and drug interactions. J Clin Oncol 1997; 15:3121–8PubMedGoogle Scholar
  33. 33.
    Gruber ML, Glass J, Choudrhi H, et al. Carboplatin chemotherapy before irradiation in newly diagnosed glioblastoma multiforme. Am J Clin Oncol 1998; 21: 338–40PubMedCrossRefGoogle Scholar
  34. 34.
    Elliott TE, Dinapoli RP, O’Fallon JR, et al. Randomized trial of radiation therapy (RT) plus dibromodulcitol (DBD) versus RT plus BCNU in high grade astrocytoma. J Neurooncol 1997; 33: 239–50PubMedCrossRefGoogle Scholar
  35. 35.
    Prados MD, Schold SC, Spence AM, et al. Phase II study of paclitaxel in patients with recurrent malignant glioma. J Clin Oncol 1996; 14: 2316–21PubMedGoogle Scholar
  36. 36.
    Chamberlain MC, Kormanik P. Salvage chemotherapy with taxol for recurrent anaplastic astrocytomas. J Neurooncol 1999; 43: 71–8PubMedCrossRefGoogle Scholar
  37. 37.
    Clarke K, Basser RL, Underhill C, et al. KNR8602 (MX2-hydrochloride): an active new agent for the treatment of recurrent high-grade glioma. J Clin Oncol 1999; 17: 2579–84PubMedGoogle Scholar
  38. 38.
    Norton L, Simon R. Tumor size, sensitivity to chemotherapy and the design of treatment schedules. Cancer Treat Rep 1977; 61: 1307–17PubMedGoogle Scholar
  39. 39.
    Levin VA, Silver P, Hannigan J, et al. Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. Int J Radiat Oncol Biol Phys 1990; 18: 321–4PubMedCrossRefGoogle Scholar
  40. 40.
    Kirby S, Macdonald D, Fisher B, et al. Pre-radiation chemotherapy for malignant glioma in adults. Can J Neurol Sci 1996; 23: 123–7PubMedGoogle Scholar
  41. 41.
    Van Eys J. Medical and oncological management of pediatric brain tumors. Prog Exp Tumor Res 1985; 29: 235–48PubMedGoogle Scholar
  42. 42.
    Van Eys J, Baram TZ, Cangir A, et al. Salvage chemotherapy for recurrent primary brain tumors in children. J Pediatr 1988; 113: 601–5PubMedCrossRefGoogle Scholar
  43. 43.
    Levin VA, Edwards MS, Wara WM, et al. 5-fluorouracil and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) followed by hydroxyurea, misonidazole, and irradiation for brainstem gliomas: a pilot study of the Brain Tumor Research Center and the Childrens Cancer Group. Neurosurgery 1984; 14: 679–81PubMedCrossRefGoogle Scholar
  44. 44.
    Ettinger LJ, Sinniah D, Siegel SE, et al. Combination chemotherapy with cyclophosphamide, vincristine, procarbazine and prednisone (COPP) in children with brain tumors. J Neurooncol 1985; 3: 263PubMedCrossRefGoogle Scholar
  45. 45.
    Pendergrass TW, Milstein JM, Geyer JR, et al. 8 drugs in 1 day chemotherapy for brain tumors: experience in 107 children and rationale for preirradiation chemotherapy. J Clin Oncol 1987; 5: 1221–31PubMedGoogle Scholar
  46. 46.
    Rozenthal JM, Robins HE, Finlay J, et al. Eight-drugs-in-one-day: chemotherapy administered before and after radiotherapy for adult patients with malignant gliomas. Cancer 1989; 63: 2475–81CrossRefGoogle Scholar
  47. 47.
    Walker RW, Allen JC, Jennings MT, et al. Continuous infusion vincristine and adriamycin in the treatment of recurrent childhood brain tumors [abstract]. Ann Neurol 1987; 22: 448Google Scholar
  48. 48.
    Rodriquez LA, Prados M, Fulton D, et al. Treatment of recurrent brainstem gliomas and other central nervous system tumors with 5-fluorouracil, CCNU, hydroxyurea and 6-mercaptopurine. Neurosurgery 1988; 22: 691–3CrossRefGoogle Scholar
  49. 49.
    Horowitz ME, Kun LE, Mulhern RK, et al. Feasibility and efficacy of preirradiation chemotherapy for pediatric brain tumors. Neurosurgery 1988; 22: 687–90PubMedCrossRefGoogle Scholar
  50. 50.
    Miser J, Krailo M, Smithson W, et al. Treatment of children with recurrent brain tumors with ifosfamide (IFOS), etoposide (VP16), and MESNA(M): results of aphase II trial [abstract]. Proc Am Soc Clin Oncol 1989; 8: 84Google Scholar
  51. 51.
    Longee DC, Friedman HS, Albright RE, et al. Treatment of patients with recurrent gliomas with cyclophosphamide and vincristine. J Neurosurg 1990; 72: 583–8PubMedCrossRefGoogle Scholar
  52. 52.
    Hildebrand J, Sahmoud T, Mignolet F, et al. Adjuvant therapy with dibromodulcitol and BCNU increases survival of adults with malignant gliomas. Neurology 1994; 44: 1479–83PubMedCrossRefGoogle Scholar
  53. 53.
    Rostomily RC, Spence AM, Duong D, et al. Multimodality management of recurrent adult malignant gliomas: results of a phase II multiagent chemotherapy study and analysis of cytoreductive surgery. Neurosurgery 1994; 35: 378–88PubMedCrossRefGoogle Scholar
  54. 54.
    Razzouk BI, Heideman RL, Friedman HS, et al. A phase II evaluation of thiotepa followed by other multiagent chemotherapy regimens in infants and young children with malignant brain tumors. Cancer 1995; 75: 2762–7PubMedCrossRefGoogle Scholar
  55. 55.
    Balmaceda C, Fetell MR, Hesdorffer C. Thiotepa and etoposide treatment of recurrent malignant gliomas: phase I study. Cancer Chemother Pharmacol 1997; 40: 72–4PubMedCrossRefGoogle Scholar
  56. 56.
    Norton L. Adjuvant breast cancer therapy: current status and future strategies — growth kinetics and the improved drug therapy of breast cancer. Semin Oncol 1999; 26: 1–4PubMedGoogle Scholar
  57. 57.
    Kellie SJ, Kovnar EH, Kun LE, et al. Neuraxis dissemination in pediatrie brain tumors. Cancer 1992; 69: 1061–6PubMedCrossRefGoogle Scholar
  58. 58.
    Geyer JR, Finlay JL, Boyett JM, et al. Survival of infants with malignant astrocytomas: a report from the Childrens Cancer Group. Cancer 1995; 75: 1045–50PubMedCrossRefGoogle Scholar
  59. 59.
    Grossman SA, Wharam M, Sheidler V, et al. Phase II study of continuous infusion carmustine and cisplatin followed by cranial irradiation in adults with newly diagnosed high-grade astrocytoma. J Clin Oncol 1997; 15: 2596–603PubMedGoogle Scholar
  60. 60.
    Kleinberg L, Grossman SA, Piantadosi S, et al. The effects of sequential versus concurrent chemotherapy and radiotherapy on survival and toxicity in patients with newly diagnosed high-grade astrocytoma. Int J Radiat Oncol Biol Phys 1999; 44: 535–43PubMedCrossRefGoogle Scholar
  61. 61.
    Lassen U, Kristjansen PEG, Wagner A, et al. Treatment of newly diagnosed glioblastoma multiforme with carmustine, cisplatin and etoposide followed by radiotherapy: a phase II study. J Neurooncol 1999; 43: 161–6PubMedCrossRefGoogle Scholar
  62. 62.
    Rajkumar SV, Buckner JC, Schomberg PJ, et al. Phase I and pharmacokinetic study of preirradiation chemotherapy with BCNU, cisplatin, etoposide and accelerated radiation therapy in patients with high grade glioma. Int J Radiat Oncol Biol Phys 1998; 42: 969–75PubMedCrossRefGoogle Scholar
  63. 63.
    Rajkumar SV, Buckner JC, Schomberg PJ, et al. Phase I evaluation of preirradiation chemotherapy with carmustine and cisplatin and accelerated radiation therapy in patients with high-grade gliomas. Neurosurgery 1999; 44: 67–73PubMedCrossRefGoogle Scholar
  64. 64.
    Hellman R, Neuberg DS, Wagner H, et al. A therapeutic trial of radiation therapy with vincristine, etoposide and procarbazine (VVP) in high grade intracranial gliomas: an Eastern Cooperative Oncology Group Study (E2392). J Neurooncol 1998; 37: 55–62PubMedCrossRefGoogle Scholar
  65. 65.
    Hildebrand J, De Witte O, Sahmoud T. Response of recurrent glioblastoma and anaplastic astrocytoma to dibromodulcitol, BCNU and procarbazine. J Neurooncol 1998; 37: 155–60PubMedCrossRefGoogle Scholar
  66. 66.
    Brandes AA, Ermani M, Turazzi S, et al. Procarbazine and high-dose tamoxifen as a second-line regimen in recurrent high grade gliomas: a phase II study. J Clin Oncol 1999; 17: 645–50PubMedGoogle Scholar
  67. 67.
    Finlay JL, Boyett JM, Yates AJ, et al. Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-one-day regimen. Childrens Cancer Group. J Clin Oncol 1995; 13: 112–23Google Scholar
  68. 68.
    Finlay JL, Geyer JR, Turski PA, et al. Pre-irradiation chemotherapy in children with high-grade astrocytoma: tumor response to two cycles of ‘8-drugs-in-1 -day’ regimen. A Childrens Cancer Group study, CCG-945. J Neurooncol 1994; 21: 255–65Google Scholar
  69. 69.
    H’sli P, Sappino AP, de Tribolet N, et al. Malignant glioma: should chemotherapy be overthrown by experimental treatments? Ann Oncol 1998; 9: 589–600CrossRefGoogle Scholar
  70. 70.
    Huncharek M, Muscat J, Geschwind J-F. Multi-drug versus single agent chemotherapy for high grade astrocytoma: results of a meta-analysis. Anticancer Res 1998; 18: 4693–8PubMedGoogle Scholar
  71. 71.
    DeAngelis LM, Burger PC, Green SB, et al. Malignant glioma: who benefits from adjuvant chemotherapy? Ann Neurol 1998; 44: 691–5CrossRefGoogle Scholar
  72. 72.
    Boiardi A, Silvani A, Milanesi I, et al. Primary glial tumor patients treated by combining cis-platin and etoposide. J Neurooncol 1991; 11: 165–70PubMedCrossRefGoogle Scholar
  73. 73.
    Duffner PK, Horowitz ME, Krischer JP, et al. Postoperative chemotherapy and delayed radiotherapy in children less than three years of age with malignant brain tumors. N Engl J Med 1991; 328: 1725–31CrossRefGoogle Scholar
  74. 74.
    Jeremic B, Shibamoto Y, Grujicic D, et al. Pre-irradiation carboplatin and etoposide and accelerated hyperfractionated radiation therapy in patients with high grade astrocytomas: a phase II study. Radiother Oncol 1999; 51: 27–33PubMedCrossRefGoogle Scholar
  75. 75.
    Sanson J, Ameri A, Monjour A, et al. Treatment of recurrent malignant supratentorial gliomas with ifosfamide, carboplatin and etoposide: a phase II study. Eur J Cancer 1996; 32A(13): 2229–35PubMedCrossRefGoogle Scholar
  76. 76.
    Castello MA, Clerico A, Deb G, et al. High-dose carboplatinum in combination with etoposide (JET regimen) for childhood brain tumors. Am J Pediatr Hematol Oncol 1990; 12: 297–300PubMedCrossRefGoogle Scholar
  77. 77.
    Corden BJ, Strauss LC, Killmond T, et al. Cisplatin, ara-C and etoposide (PAE) in the treatment of recurrent childhood brain tumors. J Neurooncol 1991; 11: 57–63PubMedCrossRefGoogle Scholar
  78. 78.
    Strauss LC, Killmond TM, Carson BS, et al. Efficacy of postoperative chemotherapy using cisplatin plus etoposide in young children with brain tumors. Med Pediatr Oncol 1991; 19: 16–21PubMedCrossRefGoogle Scholar
  79. 79.
    White L, Kellie S, Gray E, et al. Postoperative chemotherapy in children less than 4 years of age with malignant brain tumors: promising initial response to a VETOPEC-based regimen. J Pediatr Hematol Oncol 1998; 20: 125–30PubMedCrossRefGoogle Scholar
  80. 80.
    Kuhl J, Muller HL, Berthold F, et al. Preradiation chemotherapy with children and young adults with malignant brain tumors: results of the German pilot trial HIT’88/’89. Klin Padiatr 1998; 210: 227–33PubMedCrossRefGoogle Scholar
  81. 81.
    Petersdorf SH, Livingston RB. High dose chemotherapy for the treatment of malignant brain tumors. J Neurooncol 1994; 20: 155–63PubMedCrossRefGoogle Scholar
  82. 82.
    Goodwin W, Crowley J. A retrospective comparison of high dose BCNU with autologous bone marrow rescue plus radiotherapy vs. IV BCNU plus radiation therapy in high grade gliomas: a Southwest Oncology Group review [abstract]. Proc Am Soc Clin Oncol 1989; 8: 90Google Scholar
  83. 83.
    Johnson DB, Thompson JM, Corwin JA, et al. Prolongation of survival for high-grade malignant gliomas with adjuvant high-dose BCNU and autologous bone marrow transplantation. J Clin Oncol 1987; 5: 783–9PubMedGoogle Scholar
  84. 84.
    Abrey LE, Rosenblum MK, Papadopoulos E, et al. High dose chemotherapy with autologous stem cell rescue in adults with malignant primary brain tumors. J Neurooncol 1999; 44: 147–53PubMedCrossRefGoogle Scholar
  85. 85.
    Heideman RL, Douglass EC, Krance RA, et al. High-dose chemotherapy and autologous bone marrow rescue followed by interstitial and external beam radiotherapy in newly diagnosed pediatric malignant gliomas. J Clin Oncol 1993; 11: 1458–65PubMedGoogle Scholar
  86. 86.
    Graham ML, Herndon JE II, Casey JR, et al. High-dose chemotherapy with autologous stem cell rescue in patients with recurrent and high-risk pediatric brain tumors. J Clin Oncol 1997; 15: 1814–23PubMedGoogle Scholar
  87. 87.
    Dunkel IJ, Garvin Jr JH, Goldman S, et al. High dose chemotherapy with autologous bone marrow rescue for children with diffuse pontine gliomas. J Neurooncol 1998; 37: 67–73PubMedCrossRefGoogle Scholar
  88. 88.
    Mason WP, Grovas A, Halpern S, et al. Intensive chemotherapy and bone marrow rescue for young children with newly diagnosed malignant brain tumors. J Clin Oncol 1998; 16: 210–21PubMedGoogle Scholar
  89. 89.
    Kedar A, Maria BL, Graham-Pole J, et al. High-dose chemotherapy with marrow reinfusion and hyperfractionated irradiation for children with high-risk brain tumors. Med Pediatr Oncol 1994; 23: 428–36PubMedCrossRefGoogle Scholar
  90. 90.
    Bouffet E, Khelfaoui F, Philip I, et al. High-dose carmustine for high-grade gliomas in childhood. Cancer Chemother Pharmacol 1997; 39: 376–9PubMedCrossRefGoogle Scholar
  91. 91.
    Grovas AC, Boyett JM, Lindsley K, et al. Regimen-related toxicity of myeloablative chemotherapy with BCNU, thiotepa and etoposide followed by autologous stem cell rescue for children with newly diagnosed glioblastoma multiforme: report from the Childrens Cancer Group. Med Pediatr Oncol 1999; 33: 83–7PubMedCrossRefGoogle Scholar
  92. 92.
    Finlay JL, August C, Packer R, et al. High-dose multi-agent chemotherapy followed by bone marrow ‘rescue’ for malignant astrocytomas of childhood and adolescence. J Neurooncol 1990; 9: 239–48PubMedCrossRefGoogle Scholar
  93. 93.
    Finlay JL, Goldman S, Wong MC, et al. Pilot study of high-dose thiotepa and etoposide with autologous bone marrow rescue in children and young adults with recurrent CNS tumors. The Childrens Cancer Group. J Clin Oncol 1996; 14: 2495–503Google Scholar
  94. 94.
    Gururangan S, Dunkel IJ, Goldman S, et al. Myeloablative chemotherapy with autologous bone marrow rescue in young children with recurrent malignant brain tumors. J Clin Oncol 1998; 16: 2486–93Google Scholar
  95. 95.
    Goldberg SL. Peripheral blood stem cell transplantation in solid tumors other than breast cancer. Hematol Oncol Ann 1994; 2: 69–77Google Scholar
  96. 96.
    Antman KH, Elias A, Fine HA. Dose-intensive therapy with autologous bone marrow transplantation in solid tumors. In: Forman SJ, Blume KG, Thomas ED, editors. Bone marrow transplantation. Oxford: Blackwell Scientific Publications, 1994: 767–88Google Scholar
  97. 97.
    Stadtmauer EA. Peripheral blood stem cell transplantation in breast cancer. Hematol Oncol Ann 1994; 2: 61–8Google Scholar
  98. 98.
    Klumpp TR. Autologous peripheral blood stem cell transplantation versus autologous bone marrow transplantation: which is better? Hematol Oncol Ann 1994; 2: 30–8Google Scholar
  99. 99.
    Hoffman R, Murray L. Biology and mobilization of peripheral blood mononuclear cell grafts. Hematol Oncol Ann 1994; 2: 21–9Google Scholar
  100. 100.
    Mangan KF. Progress in peripheral blood stem cell transplantation. Hematol Oncol Ann 1994; 2: 15–8Google Scholar
  101. 101.
    Jakacki RI, Jamison C, Mathews VP, et al. Dose-intensification of procarbazine, CCNU (lomustine), vincristine (PCV) with peripheral blood stem cell support in young patients with gliomas. Med Pediatr Oncol 1998; 31: 483–90PubMedCrossRefGoogle Scholar
  102. 102.
    Jakacki RI, Jamison C, Heifetz SA, et al. Feasibility of sequential high-dose chemotherapy and peripheral blood stem cell support for pediatric central nervous system malignancies. Med Pediatr Oncol 1997; 29: 553–9PubMedCrossRefGoogle Scholar
  103. 103.
    Kroll RA, Neuwelt EA. Outwitting the blood-brain barrier for therapeutic purposes: osmotic opening and other means. Neurosurgery 1998; 42: 1083–1100PubMedCrossRefGoogle Scholar
  104. 104.
    Cloughesy TF, Gobin YP, Black KL, et al. Intra-arterial carboplatin chemotherapy for brain tumors: a dose escalation study based on cerebral blood flow. J Neurooncol 1997;35: 121–31PubMedCrossRefGoogle Scholar
  105. 105.
    Boiardi A, Pozzi A, Salmaggi A, et al. Safety and potential effectiveness of daunorubicin-containing liposomes in patients with advanced recurrent malignant CNS tumors. Cancer Chemother Pharmacol 1999; 43: 178–9PubMedCrossRefGoogle Scholar
  106. 106.
    Brem H, Lawson HC. The development of new brain tumor therapy utilizing local and sustained delivery of chemotherapeutic agents from biodegradable polymers. Cancer 1996; 86: 197–9CrossRefGoogle Scholar
  107. 107.
    Shenoy MA, Singh BB. Chemical radiosensitizers in cancer therapy. Cancer Invest 1992; 10: 533–51PubMedCrossRefGoogle Scholar
  108. 108.
    Phillips TL Levin VA, Ahn DK, et al. Evaluation of bromodeoxyuridine in glioblastoma multiforme: a Northern California Cancer Center Phase II study. Int J Radiat Oncol Biol Phys 1991; 21: 7009–714Google Scholar
  109. 109.
    Urtasun RC, Kinsella TJ, Farnan N, et al. Survival improvements in anaplastic astrocytoma, combining external radiation with halogenated pyrimidines: final report of RTOG 86-12, phase I–II study. Int J Radiat Oncol Biol Phys 1996; 36: 1163–7PubMedCrossRefGoogle Scholar
  110. 110.
    Greenberg HS, Chandler WF, Ensminger WD, et al. Radiosensitization with carotid intra-arterial bromodeoxyuridine + 5- fluorouracil biomodulation for malignant gliomas. Neurology 1994; 44: 1715–20PubMedCrossRefGoogle Scholar
  111. 111.
    Prados MD, Larson DA, Lamborn K, et al. Radiation therapy and hydroxyurea followed by combination of 6-thioguanine and BCNU for the treatment of primary malignant brain tumors. Int J Radiat Oncol Biol Phys 1998; 40: 57–63PubMedCrossRefGoogle Scholar
  112. 112.
    Groves MD, Maor MH, Meyers C, et al. A phase II trial of high-dose bromodeoxyuridine with accelerated fractionation radiotherapy followed by procarbazine, lomustine and vincristine for glioblastoma multiforme. Int J Radiat Oncol Biol Phys 1999; 45: 127–35PubMedCrossRefGoogle Scholar
  113. 113.
    Levin VA, Prados MR, Wara WM, et al. Radiation therapy and bromodeoxyuridine chemotherapy followed by procarbazine, lomustine and vincristine for the treatment of anaplastic gliomas. Int J Radiat Oncol Biol Phys 1995; 32: 75–83PubMedCrossRefGoogle Scholar
  114. 114.
    Sheline EG. Radiotherapy for high grade gliomas. Int J Radiat Oncol Biol Phys 1990; 18: 793–803PubMedCrossRefGoogle Scholar
  115. 115.
    Goffman TE, Dachowski LJ, Bobo H, et al. Long-term follow-up of National Cancer Institute phase I/II study of glioblastoma multiforme treated with iododeoxyuridine and hyperfractionated irradiation. J Clin Oncol 1992; 10: 264–8PubMedGoogle Scholar
  116. 116.
    Maor MH, Levin VA. Malignant gliomas. In: John MJ, Flam MS, Legha SS, et al., editors. Chemoradiation: an integrated approach to cancer treatment. Philadelphia (PA): Lea & Febiger, 1993: 191-203Google Scholar
  117. 117.
    Brown JM. Sensitizers and protectors in radiotherapy. Cancer 1985; 55: 2222–8PubMedCrossRefGoogle Scholar
  118. 118.
    Bartelink J, Bleehan NM, Phillips TL. Chemical modifiers. Int J Radiat Oncol Biol Phys 1988; 10: 1692–6Google Scholar
  119. 119.
    Mulcahy RT, Trump DL. Clinical chemosensitization by misonidazole and related compound. J Clin Oncol 1988; 6: 569–73PubMedGoogle Scholar
  120. 120.
    Huncharek M. Meta-analytic re-evaluation of misonidazole in the treatment of high grade astrocytomas. Anticancer Res 1998; 18: 1935–40PubMedGoogle Scholar
  121. 121.
    Evans RG, Kimler BF, Morantz RA, et al. A phase I/II study of the use of Fluosol as an adjuvant to radiation therapy in the treatment of primary high-grade brain tumors. Int J Radiat Oncol Biol Phys 1990; 19: 415–20PubMedCrossRefGoogle Scholar
  122. 122.
    Teicher BA, Herman TS, Lustig RA. Perfluorochemicals. Chemoradiation: an integrated approach to cancer treatment. In: John MJ, Flam MS, Legha SS, et al., editors. Philadelphia (PA): Lea & Febiger, 1993: 140–55Google Scholar
  123. 123.
    Kurimoto M, Endo S, Hirashima Y, et al. Growth inhibition and radiosensitization of cultured glioma cells by nitric oxide generating agents. J Neurooncol 1999; 42: 35–44PubMedCrossRefGoogle Scholar
  124. 124.
    Coughlin CT, Richmond RC. Biologic and clinical developments of cisplatin combined with radiation: concepts, utility, projections for new trials and the emergence of carboplatin. Semin Oncol 1989; 16: 31–43PubMedGoogle Scholar
  125. 125.
    Vokes EE, Weichselbaum RR. Concomitant chemoradiotherapy: rationale and clinical experience in patients with solid tumors. J Clin Oncol 1990; 8: 911–34PubMedGoogle Scholar
  126. 126.
    Goldie JH. Neoadjuvant combined modality therapy. Chemoradiation: an integrated approach to cancer treatment. In: John MJ, Flam MS, Legha SS, et al., editors. Philadelphia (PA): Lea & Febiger, 1993: 18–26Google Scholar
  127. 127.
    John MJ. A model for concurrent chemoradiation in clinical trials. Chemoradiation: an integrated approach to cancer treatment. In: John MJ, Flam MS, Legha SS, et al., editors. Philadelphia (PA): Lea & Febiger, 1993: 53–64Google Scholar
  128. 128.
    Looney WB, Hopkins HA. Experimental and clinical rationale for alternating chemotherapy and radiotherapy in human cancer management. Chemoradiation: an integrated approach to cancer treatment. In: John MJ, Flam MS, Legha SS, et al., editors. Philadelphia (PA): Lea & Febiger, 1993: 27–52Google Scholar
  129. 129.
    Roach M III, John MJ, Kallman RF. Alkylating agents. Chemoradiation: an integrated approach to cancer treatment. In: John MJ, Flam MS, Legha SS, et al., editors. Philadelphia (PA): Lea & Febiger, 1993: 90–103Google Scholar
  130. 130.
    Slichenmyer WJ, Rowinsky EK, Donehower RC, et al. The current status of camptothecin analogues as antitumor agents. J Natl Cancer Inst 1993; 85: 271–91PubMedCrossRefGoogle Scholar
  131. 131.
    Lamond JP, Mehta MP, Boothman DA. The potential of topoisomerase I inhibitors in the treatment of CNS malignancies: report of a synergistic effect between topotecan and radiation. J Neurooncol 1996; 30: 1–6PubMedCrossRefGoogle Scholar
  132. 132.
    Kaufmann SH, Peereboom D, Buckwalter CA, et al. Cytotoxic effects of topotecan combined with various anticancer agents in human cancer cell lines. J Natl Cancer Inst 1996; 88: 734–41PubMedCrossRefGoogle Scholar
  133. 133.
    Katz EJ, Vick JS, Kling KM, et al. Effect of topoisomerase inhibitors in cisplatin (DDP) cytotoxicity in human 2008 ovarian carcinoma cells [abstract]. Proc Annu Meet Am Assoc Cancer Res 1989; 30: A1824Google Scholar
  134. 134.
    Boothman DA, GreerS,Pardee AB. Potentiation of halogenated pyrimidine radiosensitizers in human carcinoma cells by β-lapachone (3,4-dihydro-2,2-dimethyl-2H-naphtho[l,2-b]pyran-5,6-dione), a novel DNA repair inhibitor. Cancer Res 1987; 47: 5361–7PubMedGoogle Scholar
  135. 135.
    Boothman DA, Trask DK, Pardee AB. Inhibition of potentially lethal DNA damage repair in human tumor cells by β-lapachone, an activator of topoisomerase I. Cancer Res 1989; 49: 605–12PubMedGoogle Scholar
  136. 136.
    Boothman DA, Wang M, Schea R, et al. Post-treatment exposure to camptothecin enhances the lethal effects of x-rays on radioresistant human malignant melanoma cells. Int J Radiat Oncol Biol Phys 1992; 24: 939–48PubMedCrossRefGoogle Scholar
  137. 137.
    Flam MS. Plant derivatives: vinca alkaloids, podophylotoxin derivatives. In: John MJ, Flam MS, Legha SS, et al., editors. Chemoradiation: an integrated approach to cancer treatment. Philadelphia (PA): Lea & Febiger, 1993: 120–9Google Scholar
  138. 138.
    Tishler RB, Schiff PR, Geard CR, et al. Taxol: a novel radiation sensitizer. Int J Radiat Oncol Biol Phys 1992; 22: 613–7PubMedCrossRefGoogle Scholar
  139. 139.
    Wehbe T, Glantz M, Choy H, et al. Histologie evidence of a radiosensitizing effect of Taxol in patients with astrocytomas. J Neurooncol 1998; 39: 245–51PubMedCrossRefGoogle Scholar
  140. 140.
    Glantz MJ, Chamberlain MC, Chang SM, et al. The role of paclitaxel in the treatment of primary and metastatic brain tumors. Semin Radiat Oncol 1999; 9(2 Suppl. 1): 27–33PubMedGoogle Scholar
  141. 141.
    Hildebrand JG. Chimiotherapie des gliomes malins: resultats des etudes du groupe EORTC des tumeurs cerebrales. Rev Neurol (Paris) 1992; 148: 35–440Google Scholar
  142. 142.
    Glantz MJ, Choy H, Kearns CM, et al. Weekly, outpatient paclitaxel and concurrent cranial irradiation in adults with brain tumors: preliminary results and promising directions. Semin Oncol 1995; 22: 26–32PubMedGoogle Scholar
  143. 143.
    Beauchesne P, Soler C, Rusch P, et al. Phase II study of radio-therapy-etoposide combination for patients with new malignant gliomas. Cancer Chemother Pharmacol 1999; 44: 210–6PubMedCrossRefGoogle Scholar
  144. 144.
    Fountzilas G, Karavelis A, Makrantonakis P, et al. Concurrent radiation and intracarotid cisplatin infusion in malignant gliomas: a feasibility study. Am J Clin Oncol 1997; 20: 138–42PubMedCrossRefGoogle Scholar
  145. 145.
    Levin VA, Maor MH, Thall PF, et al. Phase II study of accelerated fractionated radiation therapy with carboplatin followed by vincristine chemotherapy for the treatment of glioblastoma multiforme. Int J Radiat Oncol Biol Phys 1995; 33: 357–64PubMedCrossRefGoogle Scholar
  146. 146.
    Larner JM, Phillips CD, Dion JE, et al. A phase 1–2 trial of superselective carboplatin, low-dose infusional 5-fluorouracil and concurrent radiation for high-grade glioma. Am J Clin Oncol 1995; 18: 1–7PubMedCrossRefGoogle Scholar
  147. 147.
    Brandes AA, Rigon A, Zampieri P, et al. Carboplatin and teniposide concurrent with radiotherapy in patients with glioblastoma multiforme: a phase II study. Cancer 1998; 82: 355–61PubMedCrossRefGoogle Scholar
  148. 148.
    Walter AW, Gajjar A, Ochs JS, et al. Carboplatin and etoposide with hyperfractionated radiotherapy in children with newly diagnosed diffuse pontine gliomas: a phase I/II study. Med Pediatr Oncol 1998; 30: 28–33PubMedCrossRefGoogle Scholar
  149. 149.
    Fernandez-Hidalgo OA, Vanaclocha V, Vieitez JM, et al. High dose BCNU and autologous progenitor cell transplantation given with intra-arterial cisplatinum and simultaneous radiotherapy in the treatment of high-grade gliomas: benefit for selected patients. Bone Marrow Transplant 1996; 18: 143–9PubMedGoogle Scholar
  150. 150.
    Chamberlain MC, Kormanik P, Barba D, et al. Concurrent carboplatin and iodine-125 brachytherapy for recurrent glioblastoma multiforme. Int J Oncol 1997; 11:199–205PubMedGoogle Scholar
  151. 151.
    Loeffler JS, Shrieve DC, Coleman CN. Chemoradiation and adjuvant chemotherapy for glioblastoma: why does so much therapy yield so little improvement in survival? Int J Radiat Oncol Biol Phys 1995; 33: 531–3PubMedCrossRefGoogle Scholar
  152. 152.
    Fu KK. Biological basis for the interaction of chemotherapeutic agents and radiation therapy. Cancer 1985; 55: 2123–30PubMedCrossRefGoogle Scholar
  153. 153.
    Brandes AA, Rigon A, Zampieri P, et al. Early chemotherapy and concurrent radio-chemotherapy in high grade glioma. J Neurooncol 1996; 30: 247–55PubMedCrossRefGoogle Scholar
  154. 154.
    Rajkumar SV, Buckner JC, Schomberg PJ, et al. Phase I evaluation of preirradiation chemotherapy with carmustine and cisplatin and accelerated radiation therapy in patients with high-grade gliomas. Neurosurgery 1999; 44: 67–73PubMedCrossRefGoogle Scholar
  155. 155.
    Urban C, Benesch M, Pakisch B, et al. Synchronous radiochemotherapy in unfavorable brain tumors of children and young adults. J Neurooncol 1998; 39: 71–80PubMedCrossRefGoogle Scholar
  156. 156.
    Yung WKA, Prados MD, Yaya-Tur R, et al. Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligodendroglioma at first relapse. J Clin Oncol 1999; 17: 2762–71PubMedGoogle Scholar
  157. 157.
    Newlands ES, O’Reilly SM, Glaser MG, et al. The Charing Cross Hospital experience with temozolomide in patients with gliomas. EurJ Cancer 1996; 32A(13): 2236–41CrossRefGoogle Scholar
  158. 158.
    Brock CS, Newlands ES, Wedge SR, et al. Phase I trial of temozolomide using an extended continuous oral schedule. Cancer Res 1998; 58: 4363–67PubMedGoogle Scholar
  159. 159.
    Dancey J, Eisenhauer EA. Current perspectives on camptothecins in cancer treatment. Br J Cancer 1996; 74: 327–38PubMedCrossRefGoogle Scholar
  160. 160.
    D’Arpa P, Liu LF. Topoisomerase-targeting antitumor drugs. Biochim Biophys Acta 1989; 989: 163–77PubMedGoogle Scholar
  161. 161.
    Covey JM, Jaxel C, Kohn KW, et al. Protein-linked DNA strand breaks induced in mammalian cells by camptothecin, an inhibitor of topoisomerase I. Cancer Res 1989; 49: 5016–22PubMedGoogle Scholar
  162. 162.
    Hsiang Y-H, Liu LF. Identification of mammalian DNA topoisomerase I as an intracellular target of the anticancer drug camptothecin. Cancer Res 1988; 48: 1722–6PubMedGoogle Scholar
  163. 163.
    Hendricks CB, Rowinsky EK, Grochow LB, et al. Effects of p-glycoprotein expression on accumulation and cytotoxicity of topotecan (SK&F 104864), a new camptothecin analog. Cancer Res 1992; 52: 2268–78PubMedGoogle Scholar
  164. 164.
    Kessel D. Some determinants of camptothecin responsiveness in leukemia L1210 cells. Cancer Res 1971; 31: 1883–7PubMedGoogle Scholar
  165. 165.
    Blaney SM, Cole DE, Balis FM, et al. Plasma and cerebrospinal fluid pharmacokinetic study of topotecan in nonhuman primates. Cancer Res 1993; 53: 725–7PubMedGoogle Scholar
  166. 166.
    Hande KR, Wedlund PJ, Noone RM, et al. Pharmacokinetics of high-dose etoposide (VP-16-213) administered to cancer patients. Cancer Res 1984; 44: 379–82PubMedGoogle Scholar
  167. 167.
    Baker SK, Heideman RL, Crom WR, et al. Cerebrospinal fluid pharmacokinetics and penetration of continuous infusion topotecan in children with central nervous system tumors. Cancer Chemother Pharmacol 1996; 37: 195–202PubMedCrossRefGoogle Scholar
  168. 168.
    Blaney SM, Cole DE, Godwin K, et al. Intrathecal administration of topotecan in nonhuman primates. Cancer Chemother Pharmacol 1995; 36: 121–4PubMedCrossRefGoogle Scholar
  169. 169.
    Macdonald D, Cairncross G, Stewart D, et al. Phase II study of topotecan in patients with recurrent malignant glioma. Ann Oncol 1996; 7: 205–7PubMedCrossRefGoogle Scholar
  170. 170.
    Tubergen DG, Stewart CF, Pratt CB, et al. Phase I trial and pharmacokinetic (PK) and pharmacodynamics (PD) study of topotecan using a five day course in children with refractory solid tumors: a Pediatric Oncology Group study. J Pediatr Hematol Oncol 1996; 18: 352–61PubMedCrossRefGoogle Scholar
  171. 171.
    Blaney SMS, Phillips PC, Packer R, et al. Phase II evaluation of topotecan for pediatric central nervous system tumors. Cancer 1996; 78: 527–31PubMedCrossRefGoogle Scholar
  172. 172.
    Friedman HS, Kerby T, Fields S, et al. Topotecan treatment of adults with primary malignant glioma. Cancer 1999; 85: 1160–5PubMedCrossRefGoogle Scholar
  173. 173.
    Burch PA, Bernath AM, Cascino TL, et al. A North Central Cancer Treatment Group phase II trial of topotecan in relapsed gliomas. Invest New Drugs 2000; 18: 275–80PubMedCrossRefGoogle Scholar
  174. 174.
    Pratt CB, Stewart C, Santana VM, et al. Phase I study of topotecan in pediatric patients with malignant solid tumors. J Clin Oncol 1994; 12: 539–43PubMedGoogle Scholar
  175. 175.
    Chou T-C, Motzer RJ, Tong Y, et al. Computerized quantitation of synergism and antagonism of taxol, topotecan and cisplatin against human teratocarcinoma cell growth: a rational approach to clinical protocol design. J Natl Cancer Inst 1994; 86: 1517–24PubMedCrossRefGoogle Scholar
  176. 176.
    Rowinsky EK, Kaufmann SH, Baker SD, et al. Sequences of topotecan and cisplatin: phase I, pharmacologie, and in vitro studies to examine sequence dependence. J Clin Oncol 1996; 14: 3074–84PubMedGoogle Scholar
  177. 177.
    Pollack IF, Randall MS, Kristofik MP, et al. Effect of tamoxifen on DNA synthesis and proliferation of human malignant glioma lines in vitro. Cancer Res 1990; 50: 7134–8PubMedGoogle Scholar
  178. 178.
    Vertosick Jr FT, Selker RG, Pollack IF, et al. The treatment of intracranial malignant gliomas using orally administered tamoxifen therapy: preliminary results in a series of ‘failed’ patients. Neurosurgery 1992; 30: 897–903PubMedCrossRefGoogle Scholar
  179. 179.
    Donson AM, Weil MD, Foreman NK. Tamoxifen radiosensitization in human glioblastoma cell lines. J Neurosurg 1999; 90: 533–6PubMedCrossRefGoogle Scholar
  180. 180.
    Couldwell WT, Hinten DR, Surnock AA, et al. Treatment of recurrent malignant gliomas with chronic oral high-dose tamoxifen. Clin Cancer Res 1996; 2: 619–22PubMedGoogle Scholar
  181. 181.
    Rajkumar SV, Buckner JC, Schomberg PJ, et al. Phase I evaluation of radiation combined with recombinant interferon alpha-2a and BCNU for patients with high grade glioma. Int J Radiat Oncol Biol Phys 1998; 40: 297–302PubMedCrossRefGoogle Scholar
  182. 182.
    Shibamoto Y, Nishimura Y, Tsutui K, et al. Comparison of accelerated hyperfractionated radiotherapy and conventional radiotherapy for supratentorial malignant glioma. Jpn J Clin Oncol 1997; 27: 31–6PubMedCrossRefGoogle Scholar
  183. 183.
    Farkkila M, Jaaskelainen J, Kallio M, et al. Randomized, controlled study of intratumoral recombinant γ-interferon treatment in newly diagnosed glioblastoma. Br J Cancer 1994; 70: 138–41PubMedCrossRefGoogle Scholar
  184. 184.
    Yung WKA, Prados M, Levin VA, et al. Intravenous recombinant interferon beta in patients with recurrent malignant gliomas: a phase I/II study. J Clin Oncol 1991; 9: 1945–9PubMedGoogle Scholar
  185. 185.
    Fine HA, Wen PY, Robertson M, et al. A phase I trial of a new recombinant human β-interferon (BG9015) for the treatment of patients with recurrent gliomas. Clin Cancer Res 1997; 3: 381–7PubMedGoogle Scholar
  186. 186.
    Chang SM, Barker FG II, Huhn SL, et al. High dose oral tamoxifen and subcutaneous interferon alpha-2a for recurrent glioma. J Neurooncol 1998; 37: 169–76PubMedCrossRefGoogle Scholar
  187. 187.
    Yung WKA, Kyritsis AP, Gleason MJ, et al. Treatment of recurrent malignant gliomas with high-dose 13-cis-retinoid acid. Clin Cancer Res 1996; 2: 1931–5PubMedGoogle Scholar
  188. 188.
    Phuphanich S, Scott C, Fischbach AJ, et al. All-trans-retinoic acid: a phase II Radiation Therapy Oncology Group Study (RTOG 91-13) in patients with recurrent malignant astrocytoma. J Neurooncol 1997; 34(2): 193–200PubMedCrossRefGoogle Scholar
  189. 189.
    Malone C, Schiltz PM, Nayak SK, et al. Combination interferon-α2a and 13-cis-retinoic acid enhances radiosensitization of human malignant glioma cells in vitro. Clin Cancer Res 1999; 5: 417–23PubMedGoogle Scholar
  190. 190.
    Fine H, Loeffler J, Kyritsis A, et al. A phase II trial of the anti-angiogenic agent thalidomide in patients with recurrent high-grade glioma. Proc Am Soc Clin Oncol 1997; 16: 1372Google Scholar
  191. 191.
    Burton E, Prados M. New chemotherapy options for the treatment of malignant gliomas. Curr Opin Oncol 1999; 11: 157–61PubMedCrossRefGoogle Scholar
  192. 192.
    Stragliotto G, Vega F, Stasiecki P, et al. Multiple infusions of anti-epidermal growth factor receptor (EGFR) monoclonal antibody (EMD 55 900) in patients with recurrent malignant glioma. Eur J Cancer 1996; 32A: 636–40PubMedCrossRefGoogle Scholar
  193. 193.
    Palu G, Cavaggioni A, Calvi P, et al. Gene therapy of glioblastoma multiforme via combined expression of suicide and cytokine genes: a pilot study in humans. Gene Ther 1999; 6: 330–7PubMedCrossRefGoogle Scholar
  194. 194.
    Jennings MT, Iyengar S. The molecular genetics of therapeutic resistance in malignant astrocytomas. Am J Pharmacogenomics 2001; 1: 93–9PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2001

Authors and Affiliations

  • Mark T. Jennings
    • 1
  • Sunita Iyengar
    • 1
  1. 1.Vanderbilt Ingram Cancer CenterVanderbilt Medical SchoolNashvilleUSA

Personalised recommendations