Opinion statement
Regardless of MGMT status, standard of care for a patient with newly diagnosed glioblastoma (GBM), age ≤70 years, and adequate functional status is radiation and concurrent temozolomide followed by adjuvant temozolomide. For elderly patients, recent studies have suggested that standard radiation, hypofractionated radiation, or single agent temozolomide are acceptable treatment options. Randomized phase III studies of bevacizumab in combination with radiation and temozolomide for newly diagnosed GBM have completed accrual. Preliminary results reveal a clear progression-free survival benefit. Overall survival appears unchanged although follow-up has not fully matured and cross-over to bevacizumab upon progression among control patients may limit definitive conclusions. Although bevacizumab in the upfront setting may be considered for a subset of patients, it should not be used routinely in newly diagnosed patients until final results are available. Clinical trials evaluating promising therapeutics given in combination with standard temozolomide chemoradiation are critically needed.
Similar content being viewed by others
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
Dolecek TA, Propp JM, Stroup NE, Kruchko C. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro Oncol. 2012;14 Suppl 5:v1–v49.
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.
Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide vs radiotherapy alone on survival in glioblastoma in a randomized phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10(5):459–66.
AVAGLIO. A Study of Avastin (Bevacizumab) in combination with temozolomide and radiotherapy in patients with newly diagnosed glioblastoma. ClinicalTrials.gov Identifier NCT00943826. http://www.clinicaltrials.gov/show/NCT00943826. Accessed November, 2012.
Chinot O, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, et al. Phase III trial of bevacizumab added to standard radiotherapy and temozolomide for newly-diagnosed glioblastoma: mature progression-free survival and preliminary overall survival results in AVAglio (Abstract OT-03). Neuro Oncol. 2012;14 Suppl 6:vi101.
RTOG 0825. Temozolomide and radiation therapy with or without bevacizumab in treating patients with newly diagnosed glioblastoma. ClinicalTrials.gov Identifier NCT00884741. http://clinicaltrials.gov/ct2/show/NCT00884741. Accessed November, 2012.
Keime-Guibert F, Chinot O, Taillandier L, Cartalat-Carel S, Frenay M, Kantor G, et al. Radiotherapy for glioblastoma in the elderly. N Engl J Med. 2007;356(15):1527–35.
Roa W, Brasher PM, Bauman G, Anthes M, Bruera E, Chan A, et al. Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol. 2004;22(9):1583–8.
Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G, Simon M, et al. Temozolomide chemotherapy alone vs radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomized, phase 3 trial. Lancet Oncol. 2012;13(7):707–15. Wick et al. and Malmstrom et al. both recently published results from two phase III trials in elderly patients with newly diagnosed high-grade gliomas.
Malmstrom A, Gronberg BH, Marosi C, Stupp R, Frappaz D, Schultz H, et al. Temozolomide vs standard 6-week radiotherapy vs hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomized, phase 3 trial. Lancet Oncol. 2012;13(9):916–26. Wick et al. and Malmstrom et al. both recently published results from two phase III trials in elderly patients with newly diagnosed high-grade gliomas.
Laperriere N, Weller M, Stupp R, Perry JR, Brandes AA, Wick W, et al. Optimal management of elderly patients with glioblastoma. Cancer Treat Rev. 2013;39:350–7.
Derr RL, Ye X, Islas MU, Desideri S, Saudek CD, Grossman SA. Association between hyperglycemia and survival in patients with newly diagnosed glioblastoma. J Clin Oncol. 2009;27(7):1082–6.
Seyfried TN, Kiebish MA, Marsh J, Shelton LM, Huysentruyt LC, Mukherjee P. Metabolic management of brain cancer. Biochim Biophys Acta. 2011;1807(6):577–94.
Lawenda BD, Kelly KM, Ladas EJ, Sagar SM, Vickers A, Blumberg JB. Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy? J Natl Cancer Inst. 2008;100(11):773–83.
Sanai N, Berger MS. Recent surgical management of gliomas. Adv Exp Med Biol. 2012;746:12–25.
Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomized controlled multicenter phase III trial. Lancet Oncol. 2006;7(5):392–401.
Westphal M, Hilt DC, Bortey E, Delavault P, Olivares R, Warnke PC, et al. A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro Oncol. 2003;5(2):79–88.
Vogelbaum MA. Does extent of resection of a glioblastoma matter? Clin Neurosurg. 2012;59:79–81.
Orringer D, Lau D, Khatri S, Zamora-Berridi GJ, Zhang K, Wu C, et al. Extent of resection in patients with glioblastoma: limiting factors, perception of resectability, and effect on survival. J Neurosurg. 2012;117(5):851–9.
Chang JE, Khuntia D, Robins HI, Mehta MP. Radiotherapy and radiosensitizers in the treatment of glioblastoma multiforme. Clin Adv Hematol Oncol. 2007;5(11):894–902. 7–15.
Souhami L, Seiferheld W, Brachman D, Podgorsak EB, Werner-Wasik M, Lustig R, et al. Randomized comparison of stereotactic radiosurgery followed by conventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastoma multiforme: report of Radiation Therapy Oncology Group 93–05 protocol. Int J Radiat Oncol Biol Phys. 2004;60(3):853–60.
Gilbert M, Wang M, Aldape K, Stupp R, Hegi M, Jaeckle K, et al. RTOG 0525: A randomized phase iii trial comparing standard adjuvant temozolomide (TMZ) with a dose-dense (dd) schedule in newly diagnosed glioblastoma (GBM). Neuro Oncol. 2011;13(Supp3):Abstract NO-46.
Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorenson AG, et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010;28(11):1963–72.
Bota DA, Desjardins A, Quinn JA, Affronti ML, Friedman HS. Interstitial chemotherapy with biodegradable BCNU (Gliadel) wafers in the treatment of malignant gliomas. Ther Clin Risk Manag. 2007;3(5):707–15.
Nghiemphu P, Green RM, Pope WB, Lai A, Cloughesy TF. Safety of anticoagulation use and bevacizumab in patients with glioma. Neuro Oncol. 2008;10(3):355–60.
Norden AD, Young GS, Setayesh K, Muzikansky A, Klufas R, Ross GL, et al. Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology. 2008;70(10):779–87.
Bartolo M, Zucchella C, Pace A, Lanzetta G, Vecchione C, Grillea G, et al. Early rehabilitation after surgery improves functional outcome in inpatients with brain tumours. J Neurooncol. 2012;107(3):537–44.
Vargo M. Brain tumor rehabilitation. Am J Phys Med Rehabil. 2011;90(5 Suppl 1):S50–62.
Reardon DA, Neyns B, Weller M, Tonn JC, Nabors LB, Stupp R. Cilengitide: an RGD pentapeptide alphanubeta3 and alphanubeta5 integrin inhibitor in development for glioblastoma and other malignancies. Future Oncol. 2011;7(3):339–54.
Phuphanich S, Wheeler CJ, Rudnick JD, Mazer M, Wang H, Nuno MA, et al. Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma. Cancer Immunol Immunother. 2013;62:125–35.
Babu R, Adamson DC. Rindopepimut: an evidence-based review of its therapeutic potential in the treatment of EGFRvIII-positive glioblastoma. Core Evid. 2012;7:93–103.
Effect of NovoTTF-100A together with temozolomide in newly diagnosed glioblastoma multiforme (GBM). ClinicalTrials.gov Identifier NCT00916409. Accessed January, 2013.
MacDonald TJ, Aguilera D, Kramm CM. Treatment of high-grade glioma in children and adolescents. Neuro Oncol. 2011;13(10):1049–58.
Conflict of Interest
Eudocia Q. Lee has served on an advisory board for Novartis and has been paid for manuscript preparation by Up To Date and Continuum.
Lakshmi Nayak has served as a consultant for Genentech and Novartis.
Patrick Y. Wen has served as a consultant for Amgen, AstraZeneca, Exelixis, Eisai Co., Genentech, Merck & Co., Novartis, MedImmune, Sanofi-Aventis, and Vascular Biogenics.
David A. Reardon has served as a consultant and received honoraria from Abbott Laboratories, Abgenix, EMD Serono, Genentech/Roche, Merck/Schering, and Novartis.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lee, E.Q., Nayak, L., Wen, P.Y. et al. Treatment Options in Newly Diagnosed Glioblastoma. Curr Treat Options Neurol 15, 281–288 (2013). https://doi.org/10.1007/s11940-013-0226-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11940-013-0226-9