Journal of Neuro-Oncology

, Volume 101, Issue 2, pp 247–254 | Cite as

Temozolomide for malignant primary spinal cord glioma: an experience of six cases and a literature review

  • Wook-Ha Kim
  • Sang Hoon Yoon
  • Chae-Yong KimEmail author
  • Ki-jeong Kim
  • Min Mi Lee
  • Gheeyoung Choe
  • In-Ah Kim
  • Jee Hyun Kim
  • Yu Jung Kim
  • Hyun-Jib Kim
Clinical Study – Patient Study


Malignant primary spinal cord gliomas (PSCGs) are rare, and the optimal treatment for these lesions remains controversial. We report herein treatment outcomes of six malignant PSCGs managed with temozolomide (TMZ)-based multidisciplinary treatment. TMZ was administered concomitantly with fractionated radiotherapy for two newly diagnosed primary spinal cord glioblastoma multiforme (GBM), followed by adjuvant chemotherapy with TMZ. For one anaplastic astrocytoma (AA) and one anaplastic ependymoma (AEPN), TMZ was given as adjuvant therapy at first recurrence. One malignantly transformed ependymoma (EPN) and one malignantly transformed diffuse astrocytoma (DA) were treated with TMZ after radiotherapy at second recurrence. Two patients with newly diagnosed GBM died, 12 and 16 months, respectively, after being treated with TMZ, during and after radiation therapy. One patient with AA and one with malignantly transformed EPN showed good response to salvage therapy with TMZ and had stable disease 21 and 20 months, respectively, after TMZ treatment. One patient with recurrent AEPN and one with malignantly transformed DA died from uncontrolled progression of the lesions despite TMZ chemotherapy. Three patients developed grade 1 or 2 neutropenia, anemia, and infection. Nonhematologic toxicities occurred in all patients; however, they were below grade 3 in severity. TMZ treatment may have a positive effect on control of malignant PSCGs and survival for some patients. Specifically, treatment with TMZ during and after radiation therapy might provide survival benefit to patients with primary spinal cord GBM. A multicenter cooperative investigation for a large-scale study on malignant PSCGs may be required.


Spinal cord tumor Intramedullary Glioblastoma Anaplastic astrocytoma Anaplastic ependymoma Temozolomide 


  1. 1.
    Stein BM, McCormick PC (1992) Intramedullary neoplasms and vascular malformations. Clin Neurosurg 39:361–387PubMedGoogle Scholar
  2. 2.
    Tihan T, Chi JH, McCormick PC, Ames CP, Parsa AT (2006) Pathologic and epidemiologic findings of intramedullary spinal cord tumors. Neurosurg Clin North Am 17:7–11CrossRefGoogle Scholar
  3. 3.
    Chamberlain MC (2008) Temozolomide for recurrent low-grade spinal cord gliomas in adults. Cancer 113:1019–1024CrossRefPubMedGoogle Scholar
  4. 4.
    Weiss E, Klingebiel T, Kortmann RD, Hess CF, Bamberg M (1997) Intraspinal high-grade astrocytoma in a child—rationale for chemotherapy and more intensive radiotherapy? Childs Nerv Syst 13:108–112CrossRefPubMedGoogle Scholar
  5. 5.
    Lin YH, Huang CI, Wong TT, Chen MH, Shiau CY, Wang LW, Ming-Tak Ho D, Yen SH (2005) Treatment of spinal cord ependymomas by surgery with or without postoperative radiotherapy. J Neurooncol 71:205–210CrossRefPubMedGoogle Scholar
  6. 6.
    Raco A, Esposito V, Lenzi J, Piccirilli M, Delfini R, Cantore G (2005) Long-term follow-up of intramedullary spinal cord tumors: a series of 202 cases. Neurosurgery 56:972–981 discussion 972-981PubMedGoogle Scholar
  7. 7.
    Santi M, Mena H, Wong K, Koeller K, Olsen C, Rushing EJ (2003) Spinal cord malignant astrocytomas. Clinicopathologic features in 36 cases. Cancer 98:554–561CrossRefPubMedGoogle Scholar
  8. 8.
    Cohen AR, Wisoff JH, Allen JC, Epstein F (1989) Malignant astrocytomas of the spinal cord. J Neurosurg 70:50–54CrossRefPubMedGoogle Scholar
  9. 9.
    Nishio S, Morioka T, Fujii K, Inamura T, Fukui M (2000) Spinal cord gliomas: management and outcome with reference to adjuvant therapy. J Clin Neurosci 7:20–23CrossRefPubMedGoogle Scholar
  10. 10.
    McGirt MJ, Goldstein IM, Chaichana KL, Tobias ME, Kothbauer KF, Jallo GI (2008) Extent of surgical resection of malignant astrocytomas of the spinal cord: outcome analysis of 35 patients. Neurosurgery 63:55–60 discussion 60-51CrossRefPubMedGoogle Scholar
  11. 11.
    Fakhrai N, Neophytou P, Dieckmann K, Nemeth A, Prayer D, Hainfellner J, Marosi C (2004) Recurrent spinal ependymoma showing partial remission under Imatinib. Acta Neurochir (Wien) 146:1255–1258CrossRefGoogle Scholar
  12. 12.
    Cooper PR, Epstein F (1985) Radical resection of intramedullary spinal cord tumors in adults. Recent experience in 29 patients. J Neurosurg 63:492–499CrossRefPubMedGoogle Scholar
  13. 13.
    McCormick PC, Torres R, Post KD, Stein BM (1990) Intramedullary ependymoma of the spinal cord. J Neurosurg 72:523–532CrossRefPubMedGoogle Scholar
  14. 14.
    Volpp PB, Han K, Kagan AR, Tome M (2007) Outcomes in treatment for intradural spinal cord ependymomas. Int J Radiat Oncol Biol Phys 69:1199–1204CrossRefPubMedGoogle Scholar
  15. 15.
    Ruda R, Gilbert M, Soffietti R (2008) Ependymomas of the adult: molecular biology and treatment. Curr Opin Neurol 21:754–761CrossRefPubMedGoogle Scholar
  16. 16.
    Lee J, Parsa AT, Ames CP, McCormick PC (2006) Clinical management of intramedullary spinal ependymomas in adults. Neurosurg Clin North Am 17:21–27CrossRefGoogle Scholar
  17. 17.
    Roonprapunt C, Houten JK (2006) Spinal cord astrocytomas: presentation, management, and outcome. Neurosurg Clin North Am 17:29–36CrossRefGoogle Scholar
  18. 18.
    Lowis SP, Pizer BL, Coakham H, Nelson RJ, Bouffet E (1998) Chemotherapy for spinal cord astrocytoma: can natural history be modified? Childs Nerv Syst 14:317–321CrossRefPubMedGoogle Scholar
  19. 19.
    Doireau V, Grill J, Zerah M, Lellouch-Tubiana A, Couanet D, Chastagner P, Marchal JC, Grignon Y, Chouffai Z, Kalifa C (1999) Chemotherapy for unresectable and recurrent intramedullary glial tumours in children. Brain Tumours Subcommittee of the French Society of Paediatric Oncology (SFOP). Br J Cancer 81:835–840CrossRefPubMedGoogle Scholar
  20. 20.
    Allen JC, Aviner S, Yates AJ, Boyett JM, Cherlow JM, Turski PA, Epstein F, Finlay JL (1998) Treatment of high-grade spinal cord astrocytoma of childhood with “8-in-1” chemotherapy and radiotherapy: a pilot study of CCG-945. Children’s Cancer Group. J Neurosurg 88:215–220CrossRefPubMedGoogle Scholar
  21. 21.
    Stupp R, Dietrich PY, Ostermann Kraljevic S, Pica A, Maillard I, Maeder P, Meuli R, Janzer R, Pizzolato G, Miralbell R, Porchet F, Regli L, de Tribolet N, Mirimanoff RO, Leyvraz S (2002) Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol 20:1375–1382CrossRefPubMedGoogle Scholar
  22. 22.
    Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996CrossRefPubMedGoogle Scholar
  23. 23.
    Rovin RA, Winn R (2007) Expression of O6-methylguanine-deoxyribose nucleic acid methyltransferase and temozolomide response in a patient with a malignant spinal cord astrocytoma. Case report. J Neurosurg Spine 6:447–450CrossRefPubMedGoogle Scholar
  24. 24.
    Chamoun RB, Alaraj AM, Al Kutoubi AO, Abboud MR, Haddad GF (2006) Role of temozolomide in spinal cord low grade astrocytomas: results in two paediatric patients. Acta Neurochir (Wien) 148:175–179 discussion 180CrossRefGoogle Scholar
  25. 25.
    McLaughlin MP, Buatti JM, Marcus RB Jr, Maria BL, Mickle PJ, Kedar A (1998) Outcome after radiotherapy of primary spinal cord glial tumors. Radiat Oncol Investig 6:276–280CrossRefPubMedGoogle Scholar
  26. 26.
    Linstadt DE, Wara WM, Leibel SA, Gutin PH, Wilson CB, Sheline GE (1989) Postoperative radiotherapy of primary spinal cord tumors. Int J Radiat Oncol Biol Phys 16:1397–1403CrossRefPubMedGoogle Scholar
  27. 27.
    Jyothirmayi R, Madhavan J, Nair MK, Rajan B (1997) Conservative surgery and radiotherapy in the treatment of spinal cord astrocytoma. J Neurooncol 33:205–211CrossRefPubMedGoogle Scholar
  28. 28.
    Kim MS, Chung CK, Choe G, Kim IH, Kim HJ (2001) Intramedullary spinal cord astrocytoma in adults: postoperative outcome. J Neurooncol 52:85–94CrossRefPubMedGoogle Scholar
  29. 29.
    Katoh N, Shirato H, Aoyama H, Onimaru R, Suzuki K, Hida K, Miyasaka K, Iwasaki Y (2006) Hypofractionated radiotherapy boost for dose escalation as a treatment option for high-grade spinal cord astrocytic tumor. J Neurooncol 78:63–69CrossRefPubMedGoogle Scholar
  30. 30.
    Banczerowski P, Simo M, Sipos L, Slowik F, Benoist G, Veres R (2003) Primary intramedullary glioblastoma multiforme of the spinal cord: report of eight cases. Ideggyogy Sz 56:28–32PubMedGoogle Scholar
  31. 31.
    Choi JW, Lee MM, Kim IA, Kim JH, Choe GY, Kim CY (2008) The outcomes of concomitant chemoradiotherapy followed by adjuvant chemotherapy with temozolomide for newly diagnosed high grade gliomas: the preliminary results of single center prospective study. J Korean Neurosurg Soc 44:222–227CrossRefPubMedGoogle Scholar
  32. 32.
    Schwartz TH, McCormick PC (2000) Intramedullary ependymomas: clinical presentation, surgical treatment strategies and prognosis. J Neurooncol 47:211–218CrossRefPubMedGoogle Scholar
  33. 33.
    Waldron JN, Laperriere NJ, Jaakkimainen L, Simpson WJ, Payne D, Milosevic M, Wong CS (1993) Spinal cord ependymomas: a retrospective analysis of 59 cases. Int J Radiat Oncol Biol Phys 27:223–229PubMedGoogle Scholar
  34. 34.
    Shaw EG, Evans RG, Scheithauer BW, Ilstrup DM, Earle JD (1986) Radiotherapeutic management of adult intraspinal ependymomas. Int J Radiat Oncol Biol Phys 12:323–327CrossRefPubMedGoogle Scholar
  35. 35.
    Hoshimaru M, Koyama T, Hashimoto N, Kikuchi H (1999) Results of microsurgical treatment for intramedullary spinal cord ependymomas: analysis of 36 cases. Neurosurgery 44:264–269CrossRefPubMedGoogle Scholar
  36. 36.
    Fischer G, Mansuy L (1980) Total removal of intramedullary ependymomas: follow-up study of 16 cases. Surg Neurol 14:243–249PubMedGoogle Scholar
  37. 37.
    Schild SE, Nisi K, Scheithauer BW, Wong WW, Lyons MK, Schomberg PJ, Shaw EG (1998) The results of radiotherapy for ependymomas: the Mayo Clinic experience. Int J Radiat Oncol Biol Phys 42:953–958CrossRefPubMedGoogle Scholar
  38. 38.
    Chamberlain MC (2002) Salvage chemotherapy for recurrent spinal cord ependymona. Cancer 95:997–1002CrossRefPubMedGoogle Scholar
  39. 39.
    Chamberlain MC (2002) Etoposide for recurrent spinal cord ependymoma. Neurology 58:1310–1311PubMedGoogle Scholar
  40. 40.
    Choi JW, Kim IA, Choe GY, Kim CY (2008) Unusual manifestations of anaplastic astrocytoma with diffuse leptomeningeal seeding: a report of two cases treated using a temozolomide-based multimodal approach. J Korean Brain Tumor Soc 7:161–165Google Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Wook-Ha Kim
    • 1
  • Sang Hoon Yoon
    • 1
  • Chae-Yong Kim
    • 1
    Email author
  • Ki-jeong Kim
    • 1
  • Min Mi Lee
    • 1
  • Gheeyoung Choe
    • 2
  • In-Ah Kim
    • 3
  • Jee Hyun Kim
    • 4
  • Yu Jung Kim
    • 4
  • Hyun-Jib Kim
    • 1
  1. 1.Department of NeurosurgerySeoul National University Bundang Hospital, Seoul National University College of MedicineSeoulKorea
  2. 2.Department of PathologySeoul National University Bundang Hospital, Seoul National University College of MedicineSeoulKorea
  3. 3.Department of Radiation OncologySeoul National University Bundang Hospital, Seoul National University College of MedicineSeoulKorea
  4. 4.Department of Internal MedicineSeoul National University Bundang Hospital, Seoul National University College of MedicineSeoulKorea

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