Journal of Neuro-Oncology

, Volume 88, Issue 1, pp 97–103 | Cite as

Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in elderly patients

  • G. Minniti
  • V. De Sanctis
  • R. Muni
  • F. Filippone
  • A. Bozzao
  • M. Valeriani
  • M. F. Osti
  • U. De Paula
  • G. Lanzetta
  • V. Tombolini
  • R. Maurizi Enrici
clinical-patient studies

Abstract

Objectives The optimal treatment for elderly patients (age > 70 years) with glioblastoma remains controversial. We conducted a prospective trial in 32 consecutive elderly patients with glioblastoma who underwent surgery followed by radiotherapy (RT) plus concomitant and adjuvant temozolomide. Patients and Methods 32 patients 70 years of age or older with a newly diagnosed glioblastoma and a Karnofsky performance status (KPS) ≥ 70 were treated with RT (daily fractions of 2 Gy for a total of 60 Gy) plus temozolomide at the dose of 75 mg/m2 per day followed by six cycles of adjuvant temozolomide (150–200 mg/m2 for 5 days during each 28-day cycle). The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS) and toxicity. Results The median OS was 10.6 months and the median PFS was 7 months. The 6-month and 12-month survival rates were 91% and 37%, respectively. The 6-month and 12-month PFS rates were 56% and 16%, respectively. In multivariate analysis KPS was the only significant independent predictive factor of survival (P = 0.01). Adverse effects were mainly represented by neurotoxicity (40%), which resolved in most cases with the use of steroids, and Grade 3–4 hematologic toxicity in 28% of patients. Chemotherapy was stopped in 2 patients, delayed in 9 patients and reduced in 4 patients. Conclusions Standard RT plus concomitant and adjuvant temozolomide is a feasible treatment for elderly patients with newly diagnosed glioblastoma who present with good prognostic factors.

Keywords

Glioblastoma Elderly Radiotherapy Temozolomide 

References

  1. 1.
    Fleury A, Menegoz F, Grosclaude P et al (1997) Descriptive epidemiology of cerebral gliomas in France. Cancer 79:1195–2202PubMedCrossRefGoogle Scholar
  2. 2.
    Chakrabarti I, Cockburn M, Cozen W et al (2005) A population-based description of glioblastoma multiforme in Los Angeles County, 1974–1999. Cancer 104:2798–806PubMedCrossRefGoogle Scholar
  3. 3.
    Curran WJ Jr, Scott CB, Horton J et al (1993) Recursive partition analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. J Natl Cancer Inst 85:704–710PubMedCrossRefGoogle Scholar
  4. 4.
    Meckling S, Dold O, Forsyth PA et al (1996) Malignat supratentorial glioma in the elderly: is radiotherapy useful? Neurology 47:901–905PubMedGoogle Scholar
  5. 5.
    Shih Ha, Betensky RA, Dorfman MV et al (2005) Genetic analyses for predictors of radiation response in glioblastoma. Int J Radiat Oncol Biol Phys 63:704–711PubMedGoogle Scholar
  6. 6.
    Batchelor TT, Betensky RA, Esposito JM et al (2004) Age-dependent prognostic effects of genetic alterations in glioblastoma. Clin Cancer Res 10:228–233PubMedCrossRefGoogle Scholar
  7. 7.
    Minniti G, Brada M, Kleihues P, Ohgaki H (2006) Gliomas. In: Gospodarowicz MK, O’Sullivan B, Sobin LH (eds) Prognostic factors in cancer, 3rd edn, Wiley J &Sons, Hoboken, New JerseyGoogle Scholar
  8. 8.
    Whittle IR, Denholm SW, Gregor A et al (1991) Management of patients aged over 60 years with supratentorial glioma: lessons from an audit. Surg Neurol 36:106–111PubMedCrossRefGoogle Scholar
  9. 9.
    Bauman GS, Fisher BJ, Halperin EC et al (1994) A prospective study of short course RT in poor prognosis glioblastoma multiforme. Int J Radiat Oncol Biol Phys 29:835–839PubMedGoogle Scholar
  10. 10.
    Thomas R, James N, Guerrero D et al (1994) Hypofractionated radiotherapy as palliative treatment in poor prognosis patients with high grade glioma. Radiother Oncol 33:113–116PubMedCrossRefGoogle Scholar
  11. 11.
    Ford JM, Stenning SP, Bootle DJ et al (1997) A short fractionation radiotherapy treatment for poor prognosis patients with high grade glioma. Clin Oncol (R Coll Radiol) 9:20–24Google Scholar
  12. 12.
    Hoegler DB, Davey P (1997) A prospective study of short course radiotherapy in elderly patients with malignant glioma. J Neurooncol 33(3):201–214PubMedCrossRefGoogle Scholar
  13. 13.
    McAleese JJ, Stenning SP, Ashley S et al (2003) Hypofractionated radiotherapy for poor prognosis malignant glioma: matched pair survival analysis with MRC controls. Radiother Oncol 67:177–182PubMedCrossRefGoogle Scholar
  14. 14.
    Roa W, Brasher PMA, Bauman G et al (2004) Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol 22:1593–1598CrossRefGoogle Scholar
  15. 15.
    Keime-Guiber F, Chinot O, Taillandier L et al (2007) Radiotherapy for glioblastoma in the elderly. N Engl J Med 356:1527–1535CrossRefGoogle Scholar
  16. 16.
    Glantz M, Chamberlain M, Liu Q et al (2003) Temozolomide as an alternative to irradiation for elderly patients with newly diagnosed malignant gliomas. Cancer 97:2262–2266PubMedCrossRefGoogle Scholar
  17. 17.
    Chinot OL, Barrie M, Frauger E et al (2004) Phase II study of temozolomide without radiotherapy in newly diagnosed glioblastoma multiforme in an elderly populations. Cancer 100:2208–2214PubMedCrossRefGoogle Scholar
  18. 18.
    Chamberlain MC, Chalmers L (2007) A pilot study of primary temozolomide chemotherapy and deferred radiotherapy in elderly patients with glioblastoma. J Neurooncol 82:207–209PubMedCrossRefGoogle Scholar
  19. 19.
    Stupp R, Mason W, Van der Bent M et al (2005) Radiotherapy plus concomitant and adjuvant Temozolomide for glioblastoma. N Engl J Med 352:987–96PubMedCrossRefGoogle Scholar
  20. 20.
    MacDonald DR, Cascino TL, Schold SC Jr et al (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280PubMedGoogle Scholar
  21. 21.
    Mohan DS, Suh JH, Phan JL et al (1998) Outcome in elderly patients undergoing definitive surgery and radiation therapy for supratentorial glioblastoma multiforme at a tertiary care institution. Int J Radiat Oncol Biol Phys 42:981–987PubMedGoogle Scholar
  22. 22.
    Villà S, Vinolas N, Verger Eh et al (1998) Efficacy of radiotherapy for malignant gliomas in elderly patients. Int J Radiat Oncol Biol Phys 42:977–980PubMedGoogle Scholar
  23. 23.
    Brandes AA, Vastola F, Basso U (2003) A prospective study in glioblastoma multiforme. Cancer 3:657–662CrossRefGoogle Scholar
  24. 24.
    Gilbert MR, Armstrong TS (1996) Glial neoplasms: classification, treatment, and pathways for the future. Oncol Nurs Forum 23:615–625PubMedGoogle Scholar
  25. 25.
    Pierga JY, Hoang-Xuan K, Feuvret L et al (1999) Treatment of malignant gliomas in the elderly. J Neurooncol 43:187–193PubMedCrossRefGoogle Scholar
  26. 26.
    Piccirilli M, Landi A, Salvati M et al (2006 ) Gliomatosis cerebri treatment in 11 elderly patients. J Exp Clin Cancer Res 25:183–187PubMedGoogle Scholar
  27. 27.
    Mirimanoff RO, Gorlia T, Mason W et al (2006) Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial. Clin Oncol 24:2563–2569CrossRefGoogle Scholar
  28. 28.
    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
  29. 29.
    De Sanctis V, Mazzarella G, Osti MF et al (2006) Radiotherapy and sequential temozolomide compared with radiotherapy with concomitant and sequential temozolomide in the treatment of newly diagnosed glioblastoma multiforme. Anticancer Drugs 17:969–975PubMedCrossRefGoogle Scholar
  30. 30.
    Green H, Paul M, Vidal L et al (2007) Prophylaxis of Pneumocystis pneumonia in immunocompromised non-HIV-infected patients: systematic review and meta-analysis of randomized controlled trials. Mayo Clin Proc 82:1052–1059PubMedCrossRefGoogle Scholar
  31. 31.
    Lanzetta G, Campanella C, Rozzi A et al (2003) Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial. Anticancer Res 23:5159–5164PubMedGoogle Scholar
  32. 32.
    Aiken RD (1994) Quality-of-life issues in patients with malignant gliomas. Semin Oncol 21:273–275PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • G. Minniti
    • 1
    • 2
  • V. De Sanctis
    • 1
  • R. Muni
    • 1
  • F. Filippone
    • 1
  • A. Bozzao
    • 3
  • M. Valeriani
    • 1
  • M. F. Osti
    • 1
  • U. De Paula
    • 4
  • G. Lanzetta
    • 2
  • V. Tombolini
    • 5
  • R. Maurizi Enrici
    • 1
  1. 1.Department of Radiotherapy Oncology, S Andrea HospitalUniversity “La Sapienza”RomeItaly
  2. 2.Department of Neurological SciencesNeuromed InstitutePozzilliItaly
  3. 3.Department of Neuroradiology, S Andrea HospitalUniversity “La Sapienza”RomeItaly
  4. 4.Radiotherapy Oncology UnitSan Pietro HospitalRomeItaly
  5. 5.Department of Radiotherapy OncologyUniversity Hospital of L’AquilaL’AquilaItaly

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