Journal of Neuro-Oncology

, Volume 89, Issue 1, pp 97–103

Toxicity from chemoradiotherapy in older patients with glioblastoma multiforme

  • Angelique E. Sijben
  • John B. McIntyre
  • Gloria B. Roldán
  • Jacob C. Easaw
  • Elizabeth Yan
  • Peter A. Forsyth
  • Ian F. Parney
  • Anthony M. Magliocco
  • Hans Bernsen
  • J. Gregory Cairncross
Clinical-patient studies


Introduction Elderly patients have glioblastomas (GBM) that are aggressive and poorly responsive to treatment. They are also prone to the side effects of treatment of GBM. Methods To shed light on the treatment of elderly patients with GBM, we reviewed the treatment toxicities and survival of patients 65 years of age or older who were treated with chemoradiotherapy, which is the new standard of care for GBM in younger patients. Results Thirty-nine patients at a single cancer center in Canada met the eligibility criteria for this retrospective study. Nineteen patients were treated initially with TMZ and radiotherapy and 20 others were treated with radiotherapy alone (only two had TMZ subsequently). Eight patients in the chemoradiotherapy group (42%) experienced Grade III or IV toxicity versus none in the radiotherapy group. The median overall survival in the chemoradiotherapy group was 8.5 months (range, 2.0–24.7 months) versus 5.2 months (range, 1.5–14.2 months) in the radiotherapy group, an apparent benefit which may have been due to an imbalance in age at diagnosis, extent of resection and performance status. In this series of GBM cases, methylation of the MGMT gene promoter was not associated with longer survival, either overall, or within the chemoradiotherapy treated subset. Conclusions Elderly patients with GBM treated with chemoradiotherapy can be expected to experience significant toxicity. Large randomized trials will be necessary to determine whether chemoradiotherapy prolongs the survival of elderly patients and whether MGMT promoter status predicts benefit from temozolomide in this subset of patients.


Chemoradiotherapy Elderly patients Glioblastoma Toxicity 


  1. 1.
    Brandes A, Vastola F, Basso F et al (2003) A prospective study on glioblastoma in the elderly. Cancer 97:657–662PubMedCrossRefGoogle Scholar
  2. 2.
    Mangiola A, Maira G, De Bonis P et al (2006) Glioblastoma in the elderly: a therapeutic challenge. J Neurooncol 76:159–163PubMedCrossRefGoogle Scholar
  3. 3.
    Bauman GS, Gaspar LE, Fisher BJ et al (1994) A prospective study of short-course radiotherapy in poor prognosis glioblastoma multiforme. Int J Radiat Oncol Biol Phys 29:835–839PubMedGoogle Scholar
  4. 4.
    Villa S, Vinolas N, Verger E et al (1998) Efficacy of radiotherapy for malignant gliomas in elderly patients. Int J Radiat Oncol Biol Phys 42:977–980PubMedGoogle Scholar
  5. 5.
    Pierga JY, Hoang-Xuan K, Feuvret L et al (1999) Treatment of malignant gliomas in the elderly. J Neurooncol 43:187–193PubMedCrossRefGoogle Scholar
  6. 6.
    Gilbert MR, Bozik M, Armstrong TS et al (1996) Aggressive chemotherapy treatment of brain tumors in the elderly: results from a Phase II study [abstract]. Proc Am Soc Clin Oncol 15:271Google Scholar
  7. 7.
    Hernandez JC, Maruyama Y, Yaes R, Chin HW (1990) Accelerated fractionation radiotherapy for hospitalized glioblastoma multiforme patients with poor prognostic factors. J Neurooncol 9:41–45PubMedCrossRefGoogle Scholar
  8. 8.
    Hoegler DB, Davey P (1997) A prospective study of short course of radiotherapy in elderly patients with malignant glioma. J Neurooncol 33:201–204PubMedCrossRefGoogle Scholar
  9. 9.
    Roa W, Brasher PMA, Bauman G et al (2004) Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomised clinical trial. J Clin Oncol 22:1583–1588PubMedCrossRefGoogle Scholar
  10. 10.
    Brandes AA, Rigon A, Monfardini S (2000) Radiotherapy of the brain in elderly patients. Eur J Cancer 36:447–451PubMedCrossRefGoogle Scholar
  11. 11.
    DeAngelis LM, Delattre JY, Posner JB (1989) Radiation-induced dementia in patients cured of brain metastases. Neurology 39:789–796PubMedGoogle Scholar
  12. 12.
    Crossen JR, Garwood D, Glatstein E, Neuwelt EA (1994) Neurobehavioral sequelae of cranial irradiation in adults: a review of radiation-induced encephalopathy. J Clin Oncol 12:627–642PubMedGoogle Scholar
  13. 13.
    Meckling S, Dold O, Forsyth P, Brasher P, Hagen NA (1996) Malignant supratentorial glioma in the elderly. Is radiotherapy useful? Neurology 47:901–905PubMedGoogle Scholar
  14. 14.
    Townsley CA, Selby R, Siu LL (2005) Systematic review of barriers to the recruitment of older patients with cancer onto clinical trials. J Clin Oncol 23:3112–3124PubMedCrossRefGoogle Scholar
  15. 15.
    Food and Drug Administration (1994) November 1989 guideline for the study of drugs likely to be used in the elderly. Fed Regist 59:39398–39400. Available via: Cited 27 Aug 2007
  16. 16.
    Townsley CA, Pond GR, Oza AM et al (2006) Evaluation of adverse events experienced by older patients participating in studies of molecularly targeted agents alone or in combination. Clin Cancer Res 12:2141–2149PubMedCrossRefGoogle Scholar
  17. 17.
    Stupp R, Mason WP, Van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996PubMedCrossRefGoogle Scholar
  18. 18.
    Siu LL (2007) Clinical trials in the elderly—a concept comes of age. N Enl J Med 356:1575–1576CrossRefGoogle Scholar
  19. 19.
    Hegi ME, Diserens AC, Gorlia T et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003PubMedCrossRefGoogle Scholar
  20. 20.
    Keime-Guibert F, Chinot O, Taillandier L et al (2007) Radiotherapy for glioblastoma in the elderly. N Engl J Med 356:1527–1537PubMedCrossRefGoogle Scholar
  21. 21.
    Werner MH, Phuphanich S, Lyman GH (1995) The increasing incidence of malignant gliomas and primary central nervous system lymphoma in the elderly. Cancer 76:1634–1642PubMedCrossRefGoogle Scholar
  22. 22.
    Hernandez JC, Maruyama Y, Yaes R (1990) Accelerated fractionation radiotherapy for hospitalized glioblastoma multiforme patients with poor prognostic factors. J Neurooncol 9:41–45PubMedCrossRefGoogle Scholar
  23. 23.
    Thomas R, James N, Guerrero D, Ashley S, Gregor A, Brada M (1994) Hypofractionated radiotherapy as a palliative treatment in poor prognosis patients with high grade glioma. Radiother Oncol 33:113–116PubMedCrossRefGoogle Scholar
  24. 24.
    Curran WJ Jr, Scott CB, Horton J et al (1993) Recursive partitioning analysis of prognostic factors in three Radiation Oncology Group malignant glioma trials. J Natl Cancer Inst 85:704–710PubMedCrossRefGoogle Scholar
  25. 25.
    Barker FG II, Chang SM, Larson DA et al (2001) Age and radiation response in glioblastoma multiforme. Neurosurgery 49:1288–1297PubMedCrossRefGoogle Scholar
  26. 26.
    Rosenblum ML, Gerosa M, Dougherty DV et al (1982) Age-related chemosensitivity of stem cells from human malignant brain tumors. Lancet 1:885–887PubMedCrossRefGoogle Scholar
  27. 27.
    Grant R, Liang BC, Page MA, Crane DL, Greenberg HS, Junck LN (1995) Age influences chemotherapy response in astrocytomas. Neurology 45:929–933PubMedGoogle Scholar
  28. 28.
    Kunwar S, Mohapatra G, Bollen A, Lamborn KR, Prados M, Feuerstein BG (2001) Genetic subgroups of anaplastic astrocytomas correlate with patient age and survival. Cancer Res 61:7683–7688PubMedGoogle Scholar
  29. 29.
    Brandes AA, Monfardini S (2003) The treatment of elderly patients with high-grade gliomas. Semin Oncol 30:58–62PubMedCrossRefGoogle Scholar
  30. 30.
    Shaw EG (2004) Nothing ventured, nothing gained: treatment of glioblastoma multiforme in the elderly. J Clin Oncol 22:1540–1541PubMedCrossRefGoogle Scholar
  31. 31.
    Brandes A, Compostella A, Blatt V, Tosoni A (2006) Glioblastoma in the elderly: current and future trends. Crit Rev Oncol Hematol 600:256–266CrossRefGoogle Scholar
  32. 32.
    Norden AD, Wen PY (2006) Glioma therapy in adults. Neurologist 12:279–292PubMedCrossRefGoogle Scholar
  33. 33.
    Patwardhan RV, Shorter C, Willis BK et al (2004) Survival trends in elderly patients with glioblastoma multiforme: resective surgery, radiation, and chemotherapy. Surg Neurol 62:207–215PubMedCrossRefGoogle Scholar
  34. 34.
    Combs S, Wagner J, Bischof M et al (2007) Postoperative treatment of primary glioblastoma multiforme with radiation and concomitant temozolomide in elderly patients. Int J Radiat Oncol Biol Phys (in press). doi:10.1016/j.ijrobp.2007.07.2368
  35. 35.
    Vuorinen V, Hinkka S, Farkkila M et al (2003) Debulking or biopsy of malignant glioma in elderly people: a randomised study. Acta Neurochir (Wien) 145:5–10CrossRefGoogle Scholar
  36. 36.
    Kelly P, Hunt C (1994) The limited value of cytoreductive surgery in elderly patients with malignant gliomas. Neurosurgery 34:62–67PubMedCrossRefGoogle Scholar
  37. 37.
    Lacroix M, Abi-Said D, Fourney DR et al (2001) A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95:190–198PubMedCrossRefGoogle Scholar
  38. 38.
    Laws ER, Parney IF, Huang W et al (2003) Survival following surgery and prognostic factors for recently diagnosed malignant glioma: data from the Glioma Outcomes Project. J Neurosurg 99:467–473PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Angelique E. Sijben
    • 1
  • John B. McIntyre
    • 2
    • 3
    • 4
  • Gloria B. Roldán
    • 2
    • 4
    • 5
  • Jacob C. Easaw
    • 2
    • 4
  • Elizabeth Yan
    • 2
    • 4
  • Peter A. Forsyth
    • 2
    • 4
  • Ian F. Parney
    • 4
    • 5
  • Anthony M. Magliocco
    • 3
    • 4
  • Hans Bernsen
    • 1
  • J. Gregory Cairncross
    • 4
    • 5
  1. 1.Department of NeurologyCanisius Wilhelmina HospitalNijmegenThe Netherlands
  2. 2.Department of OncologyTom Baker Cancer CentreCalgaryCanada
  3. 3.Department of Pathology and Laboratory MedicineUniversity of CalgaryCalgaryCanada
  4. 4.Clark Smith Brain Tumor CenterCalgaryCanada
  5. 5.Department of Clinical NeurosciencesFoothills Medical Centre, University of CalgaryCalgaryCanada

Personalised recommendations