Skip to main content
Springer Nature Link
Log in

Toxicity from chemoradiotherapy in older patients with glioblastoma multiforme

  • Clinical-patient studies
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Explore related subjects

Discover the latest articles and news from researchers in related subjects, suggested using machine learning.

References

  1. Brandes A, Vastola F, Basso F et al (2003) A prospective study on glioblastoma in the elderly. Cancer 97:657–662

    Article  PubMed  Google Scholar 

  2. Mangiola A, Maira G, De Bonis P et al (2006) Glioblastoma in the elderly: a therapeutic challenge. J Neurooncol 76:159–163

    Article  PubMed  CAS  Google Scholar 

  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 29:835–839

    PubMed  CAS  Google Scholar 

  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 42:977–980

    PubMed  CAS  Google Scholar 

  5. Pierga JY, Hoang-Xuan K, Feuvret L et al (1999) Treatment of malignant gliomas in the elderly. J Neurooncol 43:187–193

    Article  PubMed  CAS  Google Scholar 

  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 15:271

    Google Scholar 

  7. Hernandez JC, Maruyama Y, Yaes R, Chin HW (1990) Accelerated fractionation radiotherapy for hospitalized glioblastoma multiforme patients with poor prognostic factors. J Neurooncol 9:41–45

    Article  PubMed  CAS  Google Scholar 

  8. Hoegler DB, Davey P (1997) A prospective study of short course of radiotherapy in elderly patients with malignant glioma. J Neurooncol 33:201–204

    Article  PubMed  CAS  Google Scholar 

  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 22:1583–1588

    Article  PubMed  CAS  Google Scholar 

  10. Brandes AA, Rigon A, Monfardini S (2000) Radiotherapy of the brain in elderly patients. Eur J Cancer 36:447–451

    Article  PubMed  CAS  Google Scholar 

  11. DeAngelis LM, Delattre JY, Posner JB (1989) Radiation-induced dementia in patients cured of brain metastases. Neurology 39:789–796

    PubMed  CAS  Google Scholar 

  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 12:627–642

    PubMed  CAS  Google Scholar 

  13. Meckling S, Dold O, Forsyth P, Brasher P, Hagen NA (1996) Malignant supratentorial glioma in the elderly. Is radiotherapy useful? Neurology 47:901–905

    PubMed  CAS  Google Scholar 

  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 23:3112–3124

    Article  PubMed  Google Scholar 

  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: http://www.fda.gov/cder/guidance/iche7.pdf. Cited 27 Aug 2007

  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 12:2141–2149

    Article  PubMed  CAS  Google Scholar 

  17. Stupp R, Mason WP, Van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996

    Article  PubMed  CAS  Google Scholar 

  18. Siu LL (2007) Clinical trials in the elderly—a concept comes of age. N Enl J Med 356:1575–1576

    Article  CAS  Google Scholar 

  19. Hegi ME, Diserens AC, Gorlia T et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003

    Article  PubMed  CAS  Google Scholar 

  20. Keime-Guibert F, Chinot O, Taillandier L et al (2007) Radiotherapy for glioblastoma in the elderly. N Engl J Med 356:1527–1537

    Article  PubMed  CAS  Google Scholar 

  21. Werner MH, Phuphanich S, Lyman GH (1995) The increasing incidence of malignant gliomas and primary central nervous system lymphoma in the elderly. Cancer 76:1634–1642

    Article  PubMed  CAS  Google Scholar 

  22. Hernandez JC, Maruyama Y, Yaes R (1990) Accelerated fractionation radiotherapy for hospitalized glioblastoma multiforme patients with poor prognostic factors. J Neurooncol 9:41–45

    Article  PubMed  CAS  Google Scholar 

  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 33:113–116

    Article  PubMed  CAS  Google Scholar 

  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 85:704–710

    Article  PubMed  Google Scholar 

  25. Barker FG II, Chang SM, Larson DA et al (2001) Age and radiation response in glioblastoma multiforme. Neurosurgery 49:1288–1297

    Article  PubMed  Google Scholar 

  26. Rosenblum ML, Gerosa M, Dougherty DV et al (1982) Age-related chemosensitivity of stem cells from human malignant brain tumors. Lancet 1:885–887

    Article  PubMed  CAS  Google Scholar 

  27. Grant R, Liang BC, Page MA, Crane DL, Greenberg HS, Junck LN (1995) Age influences chemotherapy response in astrocytomas. Neurology 45:929–933

    PubMed  CAS  Google Scholar 

  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 61:7683–7688

    PubMed  CAS  Google Scholar 

  29. Brandes AA, Monfardini S (2003) The treatment of elderly patients with high-grade gliomas. Semin Oncol 30:58–62

    Article  PubMed  Google Scholar 

  30. Shaw EG (2004) Nothing ventured, nothing gained: treatment of glioblastoma multiforme in the elderly. J Clin Oncol 22:1540–1541

    Article  PubMed  Google Scholar 

  31. Brandes A, Compostella A, Blatt V, Tosoni A (2006) Glioblastoma in the elderly: current and future trends. Crit Rev Oncol Hematol 600:256–266

    Article  Google Scholar 

  32. Norden AD, Wen PY (2006) Glioma therapy in adults. Neurologist 12:279–292

    Article  PubMed  Google Scholar 

  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 62:207–215

    Article  PubMed  Google Scholar 

  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. Vuorinen V, Hinkka S, Farkkila M et al (2003) Debulking or biopsy of malignant glioma in elderly people: a randomised study. Acta Neurochir (Wien) 145:5–10

    Article  CAS  Google Scholar 

  36. Kelly P, Hunt C (1994) The limited value of cytoreductive surgery in elderly patients with malignant gliomas. Neurosurgery 34:62–67

    Article  PubMed  CAS  Google Scholar 

  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 95:190–198

    Article  PubMed  CAS  Google Scholar 

  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 99:467–473

    PubMed  Google Scholar 

Download references

Acknowledgments

The authors wish to thank the Alberta Heritage Foundation for Medical Research, the Alberta Cancer Foundation and the Hotchkiss Brain Institute for sponsoring this research. AES is indebted to Drs Prick and Jeuken, Nijmegen, The Netherlands, for their guidance.

Author information

Authors and Affiliations

  1. Department of Neurology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands

    Angelique E. Sijben & Hans Bernsen

  2. Department of Oncology, Tom Baker Cancer Centre, Calgary, AB, Canada

    John B. McIntyre, Gloria B. Roldán, Jacob C. Easaw, Elizabeth Yan & Peter A. Forsyth

  3. Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada

    John B. McIntyre & Anthony M. Magliocco

  4. Clark Smith Brain Tumor Center, Calgary, AB, Canada

    John B. McIntyre, Gloria B. Roldán, Jacob C. Easaw, Elizabeth Yan, Peter A. Forsyth, Ian F. Parney, Anthony M. Magliocco & J. Gregory Cairncross

  5. Department of Clinical Neurosciences, Foothills Medical Centre, University of Calgary, 1403 29th Street NW, Calgary, AB, Canada, T2N 2T9

    Gloria B. Roldán, Ian F. Parney & J. Gregory Cairncross

Authors
  1. Angelique E. Sijben
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. John B. McIntyre
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Gloria B. Roldán
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Jacob C. Easaw
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Elizabeth Yan
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Peter A. Forsyth
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Ian F. Parney
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Anthony M. Magliocco
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Hans Bernsen
    View author publications

    You can also search for this author inPubMed Google Scholar

  10. J. Gregory Cairncross
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to J. Gregory Cairncross.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sijben, A.E., McIntyre, J.B., Roldán, G.B. et al. Toxicity from chemoradiotherapy in older patients with glioblastoma multiforme. J Neurooncol 89, 97–103 (2008). https://doi.org/10.1007/s11060-008-9593-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-008-9593-6

Keywords