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Chemotherapeutic options for primary brain tumors

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Opinion statement

Malignant gliomas are the most common primary brain tumors. Despite intensive clinical investigation and many novel therapeutic approaches, treatment for most primary brain tumors remains inadequate. Most are associated with a high rate of recurrence after primary therapy and a dismal outcome following recurrence. Surgery and radiation remain the primary modalities of therapy for malignant brain tumors. The role of chemotherapy in malignant gliomas, especially glioblastoma multiforme, has been inconclusive. However, a recent trial by the European Organisation for Research and Treatment of Cancer and the National Cancer Institute of Canada combining radiation therapy with temozolomide for newly diagnosed glioblastoma patients showed a significantly improved survival benefit over radiation therapy alone. In addition to this encouraging progress, recent experience has shown that selected malignant brain tumors—for example, anaplastic oligodendrogliomas, primary central nervous system lymphomas, medulloblastomas, and intracranial germ cell tumors—are often highly responsive to chemotherapy. Molecular genetic studies are becoming indispensable aids in the diagnosis and treatment of the malignant gliomas. For example, we have learned that allelic loss of chromosome 1p is a significant predictor of chemosensitivity, whereas combined loss of chromosomes 1p and 19q is a strong predictor of chemosensitivity, progression-free survival, and overall survival in patients with anaplastic oligodendroglioma. Similarly, MGMT promoter methylation is associated with more frequent responses and longer survival in patients with glioblastoma multiforme receiving temozolomide-based therapy. These and other recent advances have led to the development and testing of several novel chemotherapeutic and molecular-targeted agents. Several different approaches and modalities to improve the efficacy of chemotherapy (eg, MGMT promoter methylation) are currently under way. Clinical trials implementing angiogenesis inhibitors, biologic modifiers, or molecular-targeted therapies are also actively being investigated.

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References and Recommended Reading

  1. Jemal A, Murray T, Ward E, et al.:Cancer Statistics, 2005. CA Cancer J Clin 2005, 55:10–30.

    PubMed  Google Scholar 

  2. Ries LAG, Eisner MP, Kosary CL, et al.:SEER Cancer Statistics Review:1973–1998. Bethesda, MD:National Cancer Institute; 2001.

    Google Scholar 

  3. Central Brain Tumor Registry of the United States. CBTRUS Statistical Report 2005–2006:Primary Brain Tumors in the United States Statistical Report, 1998-2002. Chicago:CBTRUS; 2005:8–50.

    Google Scholar 

  4. Brandes A, Soesan M, Fiorentino M:Medical treatment in high grade malignant gliomas in adults:an overview. Anticancer Res 1991, 11:719–728.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  6. Kristiansen K, Hagen S, Kollevold T, et al.:Combined modality therapy of operated astrocytomas grade III and IV. Confirmation of the value of postoperative irradiation and the lack of potentiation of bleomycin on survival time. Cancer 1981, 47:649–652.

    Article  PubMed  CAS  Google Scholar 

  7. Laperriere N, Zuraw L, Cairncross G ; Cancer Care Ontario Practice Guidelines Initiative Neuro-Oncology Disease Site Group:Radiotherapy for newly diagnosed malignant glioma in adults:a systemic review. Radiother Oncol 2002, 64:259–273.

    Article  PubMed  Google Scholar 

  8. Fine HA, Dear KBG, Loeffler JS, et al.:Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults. Cancer 1993, 71:2585–2597.

    Article  PubMed  CAS  Google Scholar 

  9. Stewart LA:Chemotherapy in adult high-grade gliomas:a systemic review and meta-analysis of individual patient data from 12 randomised trials. Lancet 2002, 359:1011–1018.

    Article  PubMed  CAS  Google Scholar 

  10. Stupp R, Mason WP, van den Bent MJ, et al.:Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005, 352:987–996. A landmark study that demonstrated the benefit of combined radiation therapy and temozolomide over radiation therapy alone in patients with newly diagnosed glioblastoma multiforme.

    Article  PubMed  CAS  Google Scholar 

  11. Cairncross JG, Macdonald DR:Chemotherapy for recurrent malignant oligodendroglioma. Ann Neurol 1988, 23:360–364.

    Article  PubMed  CAS  Google Scholar 

  12. Cairncross G, Macdonald D, Ludwin S, et al.:Chemotherapy for anaplastic oligodendroglioma. J Clin Oncol 1994, 12:2013–2021.

    PubMed  CAS  Google Scholar 

  13. Cairncross JG, Ueki K, Zlatescu MC, et al.:Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 1998, 90:1473–1479. A study demonstrating that deletion of the 1p and 19q chromosomes correlates with tumor response to chemo- and radiation therapy and can be used as predictive markers.

    Article  Google Scholar 

  14. Kim L, Hochberg FH, Thornton AF, et al.:Procarbazine, lomustine, and vincristine (PCV) chemotherapy for grade III and grade IV oligoastrocytomas. J Neurosurg 1996, 85:602–607.

    PubMed  CAS  Google Scholar 

  15. van den Bent MJ, Taphoorn MJ, Brandes AA, et al.:Phase II study of first-line chemotherapy with temozolomide in recurrent oligodendroglial tumors:the European Organization for Research and Treatment of Cancer Brain Tumor Group Study 26971. J Clin Oncol 2003, 21:2525–2528.

    Article  PubMed  CAS  Google Scholar 

  16. Shaw EG, Wisoff JH:Prospective clinical trials of intracranial low-grade glioma in adults and children. Neuro-oncol 2003, 5:153–160.

    Article  PubMed  Google Scholar 

  17. Stenning SP, Freedman LS, Bleehen NM:An overview of published results from randomized studies of nitrosoureas in primary high grade malignant glioma. Br J Cancer 1987, 56:89–90.

    PubMed  CAS  Google Scholar 

  18. Westphal M, Hilt DC, Bortey E:A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro-oncol 2003, 5:79–88.

    Article  PubMed  CAS  Google Scholar 

  19. Scott JN, Rewcastle NB, Brasher PM, et al.:Which glioblastoma multiforme patient will become a long-term survivor? A population-based study. Ann Neurol 1999, 46:183–188.

    Article  PubMed  CAS  Google Scholar 

  20. Salcman M, Scholtz H, Kaplan RS, et al.:Long-term survival in patients with malignant astrocytoma. Neurosurgery 1994, 34:213–220.

    Article  PubMed  CAS  Google Scholar 

  21. Vandenberg SR, Lopes MBS:Classification. In The Gliomas.Edited by Burger MS, Wilson CB. Philadelphia:WB Saunders; 1999:172–191.

    Google Scholar 

  22. Burger PC, Scheithauer B, Vogel FS:Surgical Pathology of the Nervous System and Its Coverings, edn 3. New York:Churchill Livingston; 1991:306–324.

    Google Scholar 

  23. Sarkar C, Roy S, Tandon PN:Oligodendroglial tumors. An immunohistochemical and electron microscopic study. Cancer 1988, 61:1862–1866.

    Article  PubMed  CAS  Google Scholar 

  24. Kraus JA, Koopmann J, Kaskel P, et al.:Shared allelic losses on chromosomes 1p and 19q suggest a common origin of oligodendroglioma and oligoastrocytoma. J Neuropathol Exp Neurol 1995, 54:91–95.

    PubMed  CAS  Google Scholar 

  25. Louis DN, Gusella JF:A tiger behind many doors:multiple pathways to malignant glioma. Trends Genet 1995, 11:412–415.

    Article  PubMed  CAS  Google Scholar 

  26. Herpers MJHM, Budka H:Glial fibrillary acidic protein (GFAP) in oligodendroglial tumors:gliofibrillary oligodendroglioma and transitional oligoastrocytoma as subtypes of oligodendroglioma. Acta Neuropathol 1984, 64:265–272.

    Article  PubMed  CAS  Google Scholar 

  27. Batchelor T, Loeffler JS:Primary CNS lymphoma. J Clin Oncol 2006, 24:1281–1288.

    Article  PubMed  CAS  Google Scholar 

  28. Nelson DF, Martz KL, Bonner H, et al.:Non-Hodgkin's lymphoma of the brain:can high dose, large volume radiation therapy improve survival? Report on a prospective trial by the Radiation Therapy Oncology Group (RTOG):RTOG 8315. Int J Radiat Oncol Biol Phys 1992, 23:9–17.

    PubMed  CAS  Google Scholar 

  29. Glass J, Gruber ML, Cher L, Hochberg FH:Preirradiation methotrexate chemotherapy of primary central nervous system lymphoma:long-term outcome. J Neurosurg 1994, 81:188–195.

    PubMed  CAS  Google Scholar 

  30. DeAngelis LM, Yahalom J, Thaler HT, Kher U:Combined modality therapy for primary CNS lymphoma. J Clin Oncol 1992, 10:635–643.

    PubMed  CAS  Google Scholar 

  31. Neuwelt EA, Goldman DL, Dahlborg SA, et al.:Primary CNS lymphoma treated with osmotic blood-brain barrier disruption:prolonged survival and preservation of cognitive function. J Clin Oncol 1991, 9:1580–1590.

    PubMed  CAS  Google Scholar 

  32. Lachance DH, Brizel DM, Gockerman JP, et al.:Cyclophosphamide, doxorubicin, vincristine, and prednisone for primary central nervous system lymphoma:short-duration response, multifocal intracerebral recurrence preceding radiotherapy. Neurology 1994, 44:1721–1727.

    PubMed  CAS  Google Scholar 

  33. DeAngelis LM:Current management of primary central nervous system lymphoma. Oncology 1995, 9:63–71.

    PubMed  CAS  Google Scholar 

  34. Batchelor T, Carson K, O'Neill A, et al.:Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy:a report of NABTT 96-07. J Clin Oncol 2003, 16:1044–1049. A study that demonstrated methotrexate alone can provide response rates and durations of response comparable to those achieved with combined radiation and chemotherapy regimens and may avoid radiation-related toxicity.

    Article  CAS  Google Scholar 

  35. Glantz MJ, Cole BF, Recht L, et al.:High-dose intravenous methotrexate for patients with nonleukemic leptomeningeal cancer:is intrathecal chemotherapy necessary? J Clin Oncol 1998, 16:1561–1567.

    PubMed  CAS  Google Scholar 

  36. Brem H, Piantadosi S, Burger PC et al.:Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-Brain Tumor Treatment Group. Lancet 1995, 345:1008–1012.

    Article  PubMed  CAS  Google Scholar 

  37. Hegi ME, Diserens AC, Gorlia T, et al.:MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005, 352:997–1003. This study demonstrated that MGMT promoter methylation is associated with more frequent responses and longer survival in patients with glioblastoma multiforme receiving temozolomide-based therapy.

    Article  PubMed  CAS  Google Scholar 

  38. Cairncross JG, McDonald DR:Successful chemotherapy for recurrent malignant oligodendroglioma. Ann Neurol 1988, 23:360–364.

    Article  PubMed  CAS  Google Scholar 

  39. McDonald DR, Gaspar LE, Cairncross JG, et al.:Successful chemotherapy for newly diagnosed aggressive oligodendroglioma. Ann Neurol 1990, 27:573–574.

    Article  Google Scholar 

  40. Jackle KA, Ballman KV, Rao RD, et al.:Current strategies in treatment of oligodendroglioma:evolution of molecular signatures of response. J Clin Oncol 2006, 24:1246–1252.

    Article  CAS  Google Scholar 

  41. Hoang-Xuan K, Capelle L, Kujas M, et al.:Temozolomide as initial treatment for adults with low-grade oligodendrogliomas or oligoastrocytomas and correlation with chromosome 1p deletions. J Clin Oncol 2004, 22:3133–3138.

    Article  PubMed  CAS  Google Scholar 

  42. Chinot OL, Honore S, Dufour H, et al.:Safety and efficacy of temozolomide in patients with recurrent anaplastic oligodendrogliomas after standard radiotherapy and chemotherapy. J Clin Oncol 2001, 19:2449–2455.

    PubMed  CAS  Google Scholar 

  43. Scopece L, Franceschi E, Cavallo G, et al.:Carboplatin and etoposide (CE) chemotherapy in patients with recurrent or progressive oligodendroglial tumors. J Neurooncol 2006, In press.

  44. Abrey LE, Childs BH, Paleologos N, et al.:High-dose chemotherapy with stem cell rescue as initial therapy for anaplastic oligodendroglioma:long-term followup. Neuro-oncol 2006, 2:183–188.

    Article  CAS  Google Scholar 

  45. Veninga T, Langendijk HA, Slotman BJ, et al.:Reirradiation of primary brain tumours:survival, clinical response and prognostic factors. Radiother Oncol 2001, 59:127–137.

    Article  PubMed  CAS  Google Scholar 

  46. Glass J, Hochberg FH, Gruber ML, et al.:The treatment of oligodendrogliomas and mixed oligodendrogliomaastrocytomas with PCV chemotherapy. J Neurosurg 1992, 76:741–745.

    Article  PubMed  CAS  Google Scholar 

  47. Kyritsis AP, Yung WKA, Bruner J, et al.:The treatment of anaplastic oligodendrogliomas and mixed gliomas. Neurosurgery 1993, 32:365–371.

    Article  PubMed  CAS  Google Scholar 

  48. DeAngelis LM, Yahalom J, Thaler HT, et al.:Combined modality therapy for primary CNS lymphoma. J Clin Oncol 1992, 10:635–643.

    PubMed  CAS  Google Scholar 

  49. Omuro AM, Ben-Porat LS, Panageas KS, et al.:Delayed neurotoxicity in primary central nervous system lymphoma. Arch Neurol 2005, 62:1595–1600.

    Article  PubMed  Google Scholar 

  50. Fischer L, Thiel E, Klasen HA, et al.:Prospective trial on topotecan salvage therapy in primary CNS lymphoma. Ann Oncol 2006, 17:1141–1145.

    Article  PubMed  CAS  Google Scholar 

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Kim, L., Glantz, M. Chemotherapeutic options for primary brain tumors. Curr. Treat. Options in Oncol. 7, 467–478 (2006). https://doi.org/10.1007/s11864-006-0022-9

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