Combined Hydroxyurea and Verapamil in the Clinical Treatment of Refractory Meningioma: Human and Orthotopic Xenograft Studies

Karsy, Michael; Hoang, Nguyen; Barth, Talmadge; Burt, Lindsay; Dunson, William A.; Gillespie, David L.; Jensen, Randy L.

doi:10.1016/j.wneu.2015.09.060

Cited by 34 publications

(19 citation statements)

References 54 publications

(25 reference statements)

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“…For example, although several studies, using primary and IOMM-Lee meningioma flank xenografts, have suggested that hydroxyurea and calcium channel blockers may bear therapeutic potential, 109,110 the combination of hydroxyurea and verapamil was ineffective in a phase I/II trial of treatment-resistant meningiomas (NCT00706810). 111 Similarly, the cyclooxygenase-2 inhibitor celecoxib showed early promise against several subcutaneous flank PDX models, including IOMM-Lee, CH157-MN, and primary grade I meningioma. 112 However, subsequent testing of intracranial PDX, developed from 4 separate primary meningiomas, showed no antitumor activity, 113 and thus further clinical studies were not pursued.…”

Section: Neuro-oncologymentioning

confidence: 99%

Molecular and translational advances in meningiomas

Suppiah

Nassiri

et al. 2019

Neuro-Oncology

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Meningiomas are the most common primary intracranial neoplasm. The current World Health Organization (WHO) classification categorizes meningiomas based on histopathological features, but emerging molecular data demonstrate the importance of genomic and epigenomic factors in the clinical behavior of these tumors. Treatment options for symptomatic meningiomas are limited to surgical resection where possible and adjuvant radiation therapy for tumors with concerning histopathological features or recurrent disease. At present, alternative adjuvant treatment options are not available in part due to limited historical biological analysis and clinical trial investigation on meningiomas. With advances in molecular and genomic techniques in the last decade, we have witnessed a surge of interest in understanding the genomic and epigenomic landscape of meningiomas. The field is now at the stage to adopt this molecular knowledge to refine meningioma classification and introduce molecular algorithms that can guide prediction and therapeutics for this tumor type. Animal models that recapitulate meningiomas faithfully are in critical need to test new therapeutics to facilitate rapid-cycle translation to clinical trials. Here we review the most up-to-date knowledge of molecular alterations that provide insight into meningioma behavior and are ready for application to clinical trial investigation, and highlight the landscape of available preclinical models in meningiomas.

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Section: Neuro-oncologymentioning

confidence: 99%

Molecular and translational advances in meningiomas

Suppiah

Nassiri

et al. 2019

Neuro-Oncology

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“…This study showed safe co-administration of CTO with temoxolomide or chemoradiation, favorable brain penetration and promising signals of activity in patients [90,91]. A Phase II study focusing on combination of verapamil and hydroxyurea (HU) for refractory meningiomas showed no effect of HU or verapamil on tumor recurrence and progression-free survival (PFS) [92].…”

Section: Targeting Calcium Signaling Pathways As a Therapeutic Appmentioning

confidence: 99%

Calcium Signaling in Brain Cancers: Roles and Therapeutic Targeting

Maklad

Sharma

Azimi

2019

Cancers

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Calcium signaling, in addition to its numerous physiological roles, is also implicated in several pathological conditions including cancer. An increasing body of evidence suggest critical roles of calcium signaling in the promotion of different aspects of cancer, including cell proliferation, therapy resistance and metastatic-related processes. In many cases, this is associated with altered expression and/or activity of some calcium channels and pumps. Brain cancers have also been the subject of many of these studies. In addition to diverse roles of calcium signals in normal brain function, a number of proteins involved in calcium transport are implicated to have specific roles in some brain cancers including gliomas, medulloblastoma, neuroblastoma and meningioma. This review discusses research that has been conducted so far to understand diverse roles of Ca2+-transporting proteins in the progression of brain cancers, as well as any attempts to target these proteins towards a therapeutic approach for the control of brain cancers. Finally, some knowledge gaps in the field that may need to be further considered are also discussed.

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“…Retrospective and prospective studies showed that hydroxyurea had an initial beneficial effect, followed by disease progression (review, [7]). However, hydroxyurea in association with imatinib [37,38] and verapamil [39] presented promising results.…”

Section: Discussionmentioning

confidence: 99%

Treatment of a Woman with Inoperable Meningioma Using Mifepristone for 26 Years

Medina-Lopes

Casulari

2020

Case Reports in Neurological Medicine

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Meningioma treatment includes observation of its growth or surgery with or without associated radiotherapy. However, drug treatment can be used for tumors deemed inoperable because of their size and location. Due to the presence of progesterone receptors, the use of antiprogestin mifepristone is recommended. This study describes a case of inoperable meningioma treated with mifepristone for 26 years without interruption. The patient is a 45-year-old woman diagnosed with plaque meningioma, extending from the bottom of her right orbit, through the length of the small wing of the sphenoid, part of the large wing of the sphenoid, especially near the superior orbital fissure, and at the ceiling of the orbit. As this meningioma was considered inoperable, treatment with 200 mg oral mifepristone was administered uninterruptedly for 26 years. This treatment initially halted the growth of the meningioma and subsequently resulted in a small reduction of its volume; however, the meningioma has persisted until the last evaluation. After five years of mifepristone use, hydroxyurea was added for nine months but was discontinued due to anemia and leucopenia. In conclusion, mifepristone was useful for the survival of the patient for those 26 years. The drug interfered with the natural history of the meningioma, which generally evolves to death in such long follow-up durations without associated surgery or radiation therapy.

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Combined Hydroxyurea and Verapamil in the Clinical Treatment of Refractory Meningioma: Human and Orthotopic Xenograft Studies

Cited by 34 publications

References 54 publications

Molecular and translational advances in meningiomas

Molecular and translational advances in meningiomas

Calcium Signaling in Brain Cancers: Roles and Therapeutic Targeting

Treatment of a Woman with Inoperable Meningioma Using Mifepristone for 26 Years

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