Medication Summary

Tamoxifen, an antiestrogen hormone, inhibits the effects of estrogen by competitively binding to estrogen receptor, producing a nuclear complex that decreases DNA synthesis and inhibits estrogen effects. Its use has been reported in small series of patients with refractory or unresectable meningiomas; in 1 study, 19 patients were included in a phase II trial. Results showed partial MRI response in 3 patients, 6 patients remained stable for a median duration of 31 months, and 10 patients had progression.^[99]

Mifepristone, RU-486 (Mifeprex), is an antiprogesterone agent. A 2015 systematic review of all studies reporting on this medication provided no evidence for benefit beyond preclinical uses.^[100]

Hydroxyurea is a chemotherapeutic agent that selectively inhibits ribonucleoside diphosphate reductase and induces apoptosis. Small case series of patients with recurrent grade II and III meningiomas have been published. Some of the these studies suggest clinical stabilization of the disease with radiologic response except in 1 patient.^[101]

Sunitinib is a tyrosine kinase inhibitor that targets VEGFR and PDGF receptor. A prospective, multicenter, single-arm phase II trial of 36 patients with recurrent WHO II and III meningioma found 42% progression-free survival at 6 months, with 5.2 months median progression-free survival and 24.6 months median overall survival. This study demonstrated that expression of VEGFR2 predicted progression-free survival of a median of 1.4 months in VEGFR2-negative patients versus 6.4 months in VEGFR2-positive patients, suggesting that VEGFR2 might be an important prognosticator in WHO II/III meningioma.^[102]

Other systemic therapies have been evaluated for recurrent meningioma, including cytotoxic chemotherapies (temozolomide, irinotecan, and combination therapy with cyclophosphamide, doxorubicin, and vincristine), biologics (interferon alfa-2b), and targeted therapies (erlotinib, gefitinib, somatostatin analogs, sunitinib, valatinib, imatinib, bevacizumab).

Class Summary

Inhibit effects of estrogen by competitively binding to estrogen receptor.

Tamoxifen (Soltamox)

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Competitively binds to estrogen receptor, producing a nuclear complex that decreases DNA synthesis and inhibits estrogen effects.

Class Summary

RU-486 has been used experimentally in the treatment of this medical condition.

Mifepristone, RU-486 (Korlym, Mifeprex)

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Experimental antiprogesterone agent. Used in patients with recurrent benign meningiomas; in one study of 14 patients, tumor regression was reported in 5 of 14 patients.

Class Summary

Agents in this class inhibit cell growth and proliferation and exhibit antiangiogenic properties.

Sunitinib (Sutent)

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This agent shows antitumor and antiangiogenic effects. May inhibit multiple-receptor tyrosine kinases, including platelet-derived growth factors, vascular endothelial growth factors, FMS-like tyrosine kinase-3, colony-stimulating factor type 1, and glial cell-line–derived neurotrophic factor receptor. Studies have shown that VEGFR2-positive patients may achieve progression-free survival of up to 6.4 months.

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Media Gallery

Coronal T1-weighted MRI with gadolinium enhancement of a sphenoid wing meningioma with some degree of encasement of bilateral cavernous sinuses.
T1-weighted MRI with gadolinium (coronal section) of same patient with sphenoid wing meningioma. A better visualization of en plaque growth of the meningioma along the convexity of the cerebral hemisphere on the left side is seen, in addition to better illustration of intracavernous carotid arteries bilaterally and en plaque growth of meningioma inferiorly and laterally around both temporal lobes.
T1-weighted gadolinium enhanced (sagittal section) of same patient with meningioma of the sphenoid wing.
CT scan brain bone window showing intraosseous meningioma involving left sphenoid wing, lateral orbital, superior orbital fissure, and the anterior part of the middle fossa floor.
MRI brain T2W (left) and T1W Fat-Sat (right) sequences showing involvement of the left sphenoid wing associated with dural thickening and the periorbita. Notice proptosis of the left globe secondary to left orbital wall thickening.
This is a typical appearance of a sphenoorbital meningioma on the MRI. The image depicts a contrasted MRI of the brain which shows an enhancing mass along the sphenoid ridge, orbital apex, and even the temporalis muscle. The orbital involvement of the tumor causes significant proptosis of the affected eye.
After elevation of the myocutaneous flap; note the underlying bone is infiltrated with tumor.
A frontotemporal craniotomy is performed to elevate the affected bone. Underlying it, dura is seen. The dura is also infiltrated with the tumor.
The tumor debulking is performed using the micro-instruments and high-speed diamond drill bit.
The dura is opened. Any intradural portion of the tumor is resected, if any. The involved dura is cut and discarded.
Important neurovascular structures are decompressed including the orbit, orbital apex, superior orbital fissure. The tumor has also infiltrated the periorbita. Some periorbital fat can be seen.
After gross total resection of the tumor (star = orbit, circle = frontal lobe, triangle = temporal lobe).
After closing the dura with a synthetic dural substitute, cranium is replaced and secured with titanium hardware. Medpore cranioplasty (white plates) are placed for further reconstruction and to restore cosmesis.

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Author

William T Couldwell, MD, PhD Professor of Neurosurgery (Adult Neurosurgery) and Joseph J Yager Chair, Department of Neurosurgery, Adjunct Professor of Surgery (Otolaryngology-Head and Neck Surgery), University of Utah School of Medicine; Attending Neurosurgeon, University of Utah Hospital

William T Couldwell, MD, PhD is a member of the following medical societies: American Academy of Neurological Surgery, American Association for the Advancement of Science, American Association of Neurological Surgeons, American College of Surgeons, American Neurological Association, California Association of Neurological Surgeons, California Medical Association, Congress of Neurological Surgeons, International Meningioma Society, Los Angeles Academy of Medicine, Los Angeles County Medical Association, Neurosurgical Society of America, New York Academy of Sciences, New York State Neurosurgical Society, North American Skull Base Society, North Dakota Medical Association, Pituitary Society, Society for Neuro-Oncology, Society of Neurological Surgeons, Utah State Neurosurgical Society, World Academy of Neurological Surgery

Disclosure: Editor in Chief for: JNS Publishing - Neurosurgical Focus.

Coauthor(s)

Bhupendra C K Patel, MD, FRCS Professor of Ophthalmic Plastic and Facial Cosmetic Surgery, Department of Ophthalmology and Visual Sciences, John A Moran Eye Center, University of Utah School of Medicine

Bhupendra C K Patel, MD, FRCS is a member of the following medical societies: American Academy of Ophthalmology, American Society of Ophthalmic Plastic and Reconstructive Surgery, Royal College of Surgeons of England, Royal Society of Medicine

Disclosure: Nothing to disclose.

Robert B Kim, MD, MS Chief Resident, Department of Neurosurgery, Clinical Neurosciences Center, University of Utah School of Medicine

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.

Chief Editor

Hampton Roy, Sr, MD † Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Additional Contributors

Andrew W Lawton, MD Neuro-Ophthalmology, Ochsner Health Services

Andrew W Lawton, MD is a member of the following medical societies: American Academy of Ophthalmology, Arkansas Medical Society, Southern Medical Association

Disclosure: Nothing to disclose.

Sally B Zachariah, MD Associate Professor, Department of Neurology, University of South Florida College of Medicine; Director, Department of Neurology, Division of Strokes, Veteran Affairs Medical Center of Bay Pines

Sally B Zachariah, MD is a member of the following medical societies: American Academy of Neurology, American Heart Association, American Society of Neuroimaging

Disclosure: Partner received none from none for none.

Gmaan Ali M Alzhrani , MBBS, MA Fellow in Skull Base and Vascular Surgery, Clinical Neuroscience Center, University of Utah School of Medicine

Gmaan Ali M Alzhrani , MBBS, MA is a member of the following medical societies: American Academy of Neurological Surgery, Congress of Neurological Surgeons, Saudi Association of Neurological Surgery

Disclosure: Nothing to disclose.

Acknowledgements

Suzan Khoromi, MD Fellow, Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Cranial Research, National Institutes of Health

Suzan Khoromi, MD is a member of the following medical societies: American Academy of Neurology, American Pain Society, and International Association for the Study of Pain

Disclosure: Nothing to disclose.

Brian R Younge, MD Professor of Ophthalmology, Mayo Clinic School of Medicine

Brian R Younge, MD is a member of the following medical societies: American Medical Association, American Ophthalmological Society, and North American Neuro-Ophthalmology Society

Disclosure: Nothing to disclose.