Medication Summary

The goals of pharmacotherapy for glioblastoma multiforme (GBM) are to reduce morbidity and to prevent complications.

Class Summary

Alkylating agents lead to DNA double strand breaks and apoptosis.

Local chemotherapy with carmustine wafers significantly prolongs survival in patients with newly diagnosed primary malignant glioma.

Temozolomide (Temodar)

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Oral alkylating approved for newly diagnosed GBM and recurrent anaplastic astrocytomas. Converted to MTIC at physiologic pH; 100% bioavailable; approximately 35% crosses blood-brain barrier. Indicated for GBM combined with radiotherapy. Significant overall survival was demonstrated in patients treated with temozolomide and radiation compared with radiotherapy alone.

Carmustine (BiCNU, Gliadel Wafer)

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Gliadel is a small wafer that contains the chemotherapeutic drug carmustine. The wafer is designed to release the drug slowly over a period of 2-3 wk after placed in tumor bed. Up to 8 wafers are implanted in the cavity, slowly delivering carmustine directly to tumor site.

Class Summary

These are monoclonal antibodies that target the vascular endothelial growth factor (VEGF) – the principal molecule involved in angiogenesis during embryogenesis and in malignant tumors – thereby inhibiting the growth of GBM

Bevacizumab (Avastin, Mvasi, Zirabev)

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Administered as an intravenous infusion in chemotherapy day unit in the hospital. FDA-approved schedule dose for recurrent glioblastoma is 10 mg/kg every 2 weeks. However, studies show even smaller doses of 5 mg/kg every 2 weeks are also equally effective. Proteinuria and hypertension are the most frequent adverse effects of the drug.

Komori T. The 2016 WHO Classification of Tumours of the Central Nervous System: The Major Points of Revision. Neurol Med Chir (Tokyo). 2017 Jul 15. 57 (7):301-311. [QxMD MEDLINE Link].
Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021 Aug 2. 23 (8):1231-1251. [QxMD MEDLINE Link].
Hamilton W, Kernick D. Clinical features of primary brain tumours: a case-control study using electronic primary care records. Br J Gen Pract. 2007 Sep. 57 (542):695-9. [QxMD MEDLINE Link].
Schmidt-Hansen M, Berendse S, Hamilton W. Symptomatic diagnosis of cancer of the brain and central nervous system in primary care: a systematic review. Fam Pract. 2015 Dec. 32 (6):618-23. [QxMD MEDLINE Link].
Stackhouse CT, Gillespie GY, Willey CD. Exploring the Roles of lncRNAs in GBM Pathophysiology and Their Therapeutic Potential. Cells. 2020 Oct 28. 9 (11):[QxMD MEDLINE Link].
Alifieris C, Trafalis DT. Glioblastoma multiforme: Pathogenesis and treatment. Pharmacol Ther. 2015 Aug. 152:63-82. [QxMD MEDLINE Link].
Louis DN. Molecular pathology of malignant gliomas. Annu Rev Pathol. 2006. 1:97-117. [QxMD MEDLINE Link].
Hardell L, Carlberg M, Söderqvist F, Mild KH, Morgan LL. Long-term use of cellular phones and brain tumours: increased risk associated with use for > or =10 years. Occup Environ Med. 2007 Sep. 64 (9):626-32. [QxMD MEDLINE Link].
Gallego O. Nonsurgical treatment of recurrent glioblastoma. Curr Oncol. 2015 Aug. 22 (4):e273-81. [QxMD MEDLINE Link].
Xu H, Chen J, Xu H, Qin Z. Geographic Variations in the Incidence of Glioblastoma and Prognostic Factors Predictive of Overall Survival in US Adults from 2004-2013. Front Aging Neurosci. 2017. 9:352. [QxMD MEDLINE Link].
Hess KR, Broglio KR, Bondy ML. Adult glioma incidence trends in the United States, 1977-2000. Cancer. 2004 Nov 15. 101 (10):2293-9. [QxMD MEDLINE Link].
Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009 May. 10 (5):459-66. [QxMD MEDLINE Link].
Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, et al. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012-2016. Neuro Oncol. 2019 Nov 1. 21 (Suppl 5):v1-v100. [QxMD MEDLINE Link].
Krex D, Klink B, Hartmann C, von Deimling A, Pietsch T, Simon M, et al. Long-term survival with glioblastoma multiforme. Brain. 2007 Oct. 130 (Pt 10):2596-606. [QxMD MEDLINE Link].
Gilbert MR, Wang M, Aldape KD, Stupp R, Hegi ME, Jaeckle KA, et al. Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. J Clin Oncol. 2013 Nov 10. 31 (32):4085-91. [QxMD MEDLINE Link].
Delgado-López PD, Corrales-García EM. Survival in glioblastoma: a review on the impact of treatment modalities. Clin Transl Oncol. 2016 Nov. 18 (11):1062-1071. [QxMD MEDLINE Link].
Luther N, Cheung NK, Souliopoulos EP, Karampelas I, Bassiri D, Edgar MA, et al. Interstitial infusion of glioma-targeted recombinant immunotoxin 8H9scFv-PE38. Mol Cancer Ther. 2010 Apr. 9 (4):1039-46. [QxMD MEDLINE Link].
Wang LF, Fokas E, Juricko J, You A, Rose F, Pagenstecher A, et al. Increased expression of EphA7 correlates with adverse outcome in primary and recurrent glioblastoma multiforme patients. BMC Cancer. 2008 Mar 25. 8:79. [QxMD MEDLINE Link].
Liang Y, Bollen AW, Aldape KD, Gupta N. Nuclear FABP7 immunoreactivity is preferentially expressed in infiltrative glioma and is associated with poor prognosis in EGFR-overexpressing glioblastoma. BMC Cancer. 2006 Apr 19. 6:97. [QxMD MEDLINE Link].
Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005 Mar 10. 352 (10):997-1003. [QxMD MEDLINE Link].
Grossman SA, Ye X, Chamberlain M, Mikkelsen T, Batchelor T, Desideri S, et al. Talampanel with standard radiation and temozolomide in patients with newly diagnosed glioblastoma: a multicenter phase II trial. J Clin Oncol. 2009 Sep 1. 27 (25):4155-61. [QxMD MEDLINE Link].
Ozawa M, Brennan PM, Zienius K, Kurian KM, Hollingworth W, Weller D, et al. The usefulness of symptoms alone or combined for general practitioners in considering the diagnosis of a brain tumour: a case-control study using the clinical practice research database (CPRD) (2000-2014). BMJ Open. 2019 Aug 30. 9 (8):e029686. [QxMD MEDLINE Link].
Leo RJ, Frodey JN, Ruggieri ML. Subtle neuropsychiatric symptoms of glioblastoma multiforme misdiagnosed as depression. BMJ Case Rep. 2020 Mar 17. 13 (3):[QxMD MEDLINE Link].
Ostrom QT, Bauchet L, Davis FG, Deltour I, Fisher JL, Langer CE, et al. The epidemiology of glioma in adults: a "state of the science" review. Neuro Oncol. 2014 Jul. 16 (7):896-913. [QxMD MEDLINE Link].
McKinnon C, Nandhabalan M, Murray SA, Plaha P. Glioblastoma: clinical presentation, diagnosis, and management. BMJ. 2021 Jul 14. 374:n1560. [QxMD MEDLINE Link].
Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021 Aug 2. 23 (8):1231-1251. [QxMD MEDLINE Link].
Rosati A, Tomassini A, Pollo B, Ambrosi C, Schwarz A, Padovani A, et al. Epilepsy in cerebral glioma: timing of appearance and histological correlations. J Neurooncol. 2009 Jul. 93 (3):395-400. [QxMD MEDLINE Link].
Yust-Katz S, Mandel JJ, Wu J, Yuan Y, Webre C, Pawar TA, et al. Venous thromboembolism (VTE) and glioblastoma. J Neurooncol. 2015 Aug. 124 (1):87-94. [QxMD MEDLINE Link].
Pichlmeier U, Bink A, Schackert G, Stummer W, ALA Glioma Study Group. Resection and survival in glioblastoma multiforme: an RTOG recursive partitioning analysis of ALA study patients. Neuro Oncol. 2008 Dec. 10 (6):1025-34. [QxMD MEDLINE Link].
Preusser M, de Ribaupierre S, Wöhrer A, Erridge SC, Hegi M, Weller M, et al. Current concepts and management of glioblastoma. Ann Neurol. 2011 Jul. 70 (1):9-21. [QxMD MEDLINE Link].
Salazar OM, Rubin P, Feldstein ML, Pizzutiello R. High dose radiation therapy in the treatment of malignant gliomas: final report. Int J Radiat Oncol Biol Phys. 1979 Oct. 5 (10):1733-40. [QxMD MEDLINE Link].
Shah JL, Li G, Shaffer JL, Azoulay MI, Gibbs IC, Nagpal S, et al. Stereotactic Radiosurgery and Hypofractionated Radiotherapy for Glioblastoma. Neurosurgery. 2018 Jan 1. 82 (1):24-34. [QxMD MEDLINE Link].
Souhami L, Scott C, Brachman D, et al. Randomized prospective comparison of stereotactic radiosurgery (SRS) followed by conventional radiotherapy (RT) with BCNU to RT with BCNU alone for selected patients with supratentorial glioblastoma multiforme (GBM): report of RTOG 93-05 protocol. International journal of Radiation Oncology, biology, Physics. OCTOBER 01, 2002. 54, issue 2, supplement:94-95. [Full Text].
Hatanaka H, Nakagawa Y. Clinical results of long-surviving brain tumor patients who underwent boron neutron capture therapy. Int J Radiat Oncol Biol Phys. 1994 Mar 30. 28 (5):1061-6. [QxMD MEDLINE Link].
Kageji T, Mizobuchi Y, Nagahiro S, Nakagawa Y, Kumada H. Long-survivors of glioblatoma treated with boron neutron capture therapy (BNCT). Appl Radiat Isot. 2011 Dec. 69 (12):1800-2. [QxMD MEDLINE Link].
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 Apr. 5 (2):79-88. [QxMD MEDLINE Link].
Darakchiev BJ, Albright RE, Breneman JC, Warnick RE. Safety and efficacy of permanent iodine-125 seed implants and carmustine wafers in patients with recurrent glioblastoma multiforme. J Neurosurg. 2008 Feb. 108 (2):236-42. [QxMD MEDLINE Link].
Perry JR, Bélanger K, Mason WP, Fulton D, Kavan P, Easaw J, et al. Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. J Clin Oncol. 2010 Apr 20. 28 (12):2051-7. [QxMD MEDLINE Link].
Rajaratnam V, Islam MM, Yang M, Slaby R, Ramirez HM, Mirza SP. Glioblastoma: Pathogenesis and Current Status of Chemotherapy and Other Novel Treatments. Cancers (Basel). 2020 Apr 10. 12 (4):[QxMD MEDLINE Link].
Blumenthal DT, Mendel L, Bokstein F. The optimal regimen of bevacizumab for recurrent glioblastoma: does dose matter?. J Neurooncol. 2016 May. 127 (3):493-502. [QxMD MEDLINE Link].

Media Gallery

T1-weighted axial gadolinium-enhanced MRI demonstrates an enhancing tumor of the right frontal lobe. Image courtesy of George Jallo, MD.
T2-weighted image demonstrates notable edema and midline shift. This finding is consistent with a high grade or malignant tumor. Image courtesy of George Jallo, MD.
Histopathologic slide demonstrating a glioblastoma multiforme.
Magnetic resonance spectroscopy is representative of a glioblastoma multiforme.

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Author

Gaurav Gupta, MD, FAANS, FACS Associate Professor of Neurosurgery, System Co-Director, Cerebrovascular and Endovascular Neurosurgery, Fellowship Director, Endovascular Neurosurgery Fellowship (Site), Department of Surgery, Division of Neurosurgery, Rutgers RWJ Barnabas Healthcare, Rutgers Robert Wood Johnson Medical School

Gaurav Gupta, MD, FAANS, FACS is a member of the following medical societies: American Academy of Neurology, American Association for the Advancement of Science, American Association of Neurological Surgeons, American College of Surgeons, American Heart Association, American Medical Association, Congress of Neurological Surgeons, Facial Pain Association, Society for Neuroscience, Society of NeuroInterventional Surgery

Disclosure: Nothing to disclose.

Coauthor(s)

Fareed R Jumah, MBBS Postdoctoral Research Fellow, Department of Neurosurgery, RWJ University Hospital, Rutgers Robert Wood Johnson Medical School

Disclosure: Nothing to disclose.

Neil Majmundar, MD Resident Physician, Department of Neurological Surgery, Rutgers New Jersey Medical School

Neil Majmundar, MD is a member of the following medical societies: American Association of Neurological Surgeons, Congress of Neurological Surgeons

Disclosure: Nothing to disclose.

Bharath Raju, MBBS, MCh Postdoctoral Research Fellow, Department of Neurosurgery, RWJ University Hospital, Rutgers Robert Wood Johnson Medical School

Bharath Raju, MBBS, MCh is a member of the following medical societies: AOSpine, Bangalore Neurological Society, European Association of Neurosurgical Societies, Neurological Society of India, Neurotrauma Society of India

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Jorge C Kattah, MD Head, Associate Program Director, Professor, Department of Neurology, University of Illinois College of Medicine at Peoria

Jorge C Kattah, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, New York Academy of Sciences

Disclosure: Nothing to disclose.

Chief Editor

Stephen A Berman, MD, PhD, MBA Professor of Neurology, University of Central Florida College of Medicine

Stephen A Berman, MD, PhD, MBA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

ABM Salah Uddin, MD Private Practice, Norwood Neurology; Consulting Staff, Department of Neurology, St Vincent's Hospital

ABM Salah Uddin, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, American Medical Association

Disclosure: Nothing to disclose.

Tambi Jarmi, MD Resident Physician, Department of Internal Medicine, Carraway Methodist Medical Center

Tambi Jarmi, MD is a member of the following medical societies: American College of Physicians, American Medical Association

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Subramanian Hariharan, MD, to the development and writing of this article.