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Meningiomas constitute the most common primary tumors of the central nervous system. Despite maximum treatment, grade 2/3 meningiomas are associated with a high risk of recurrence. Stereotactic radiosurgery is the treatment of choice as adjuvant treatment for grade 2/3 meningiomas. Currently, pharmacotherapies, including molecular targeted therapy for various growth factors, their receptors, and the associated pathways, have shown limited effectiveness for management of refractory or recurrent meningiomas. Therefore, novel systemic treatment approaches are urgently required in such cases. Recent advances in genetics and epigenetics and the identification of specific genetic alterations have led to new classifications of these tumors and the development of therapeutic targets. Identification of targeted gene mutations may lead to precision-based medicine. Other therapeutic approaches such as immune checkpoint inhibitors rarely elicit a significant response in meningiomas with a high tumor mutation burden. Combination therapies that affect these multiple targets are also considered adjuvant therapeutic options. Comprehensive/in-depth research is warranted to investigate the safety and efficacy of other treatment strategies, including chimeric antigen receptor T-cells, oncolytic virus immunotherapy, and gene therapy. In this article, we review the current evidence regarding the efficacy of systemic treatments available in the literature and discuss recent and ongoing trials for meningiomas.

We report here the regression of meningioma following treatment with the anti-estrogen agent mepitiostane in a series of cases. The first case was that of a 72-year-old woman who presented with coma status due to non-communicating hydrocephalus. A large presumed meningioma within the cerebello-pontine angle was detected on gadolinium-enhanced magnetic resonance imaging (MRI). The patient recovered from the neurological deficit following endoscopic third ventriculostomy treatment, and was administered mepitiostane (10mg/day) orally. Gadolinium-enhanced MRI showed a marked regression (85%) of the meningioma following 60 months of oral medication. The second case was that of a 79-year-old woman with no neurological deficit; however, a presumed meningioma located in the frontal skull base was detected on gadolinium-enhanced MRI. Mepitiostane (10mg/day) was administered orally. Again, a marked regression (88%) of the meningioma was demonstrated after 115 months of oral medication. The third case was that of a 71-year-old woman who presented with right visual disturbance and a visual field defect. Gadolinium-enhanced MRI demonstrated a presumed meningioma located in the left sphenoidal bone. Mepitiostane (20mg/day) was administered orally. An 79% regression of the meningioma was observed after 21 months of oral medication. In these three cases, the marked reduction in meningioma following anti-estrogen agent (mepitiostane) administration suggested that this oral medication could be an effective therapeutic option in elderly patients.

We report a case with malignant meningioma in which new preliminary treatment trial was performed by chemotherapy using anti-cancer drugs selected on the basis of multidrug resistance gene mRNA expression, such as MDR1, MGMT, MRP1, MRP2, MXR1, and DNA topoisomerase II alpha, from RT-PCR assay. A 43-year-old female had been operated for parasagittal anaplastic meningioma three times because of recurrences. partial removal of tumor was performed at the 3rd operation. RT-PCR assay of this tissue revealed overexpression of MDR1, MRP1, MRP2 and MGMT mRNA, but no ABCG 2 expression was observed. The patient was given mitoxantrone and hydroxyurea following irradiation, after which the tumor did not recur for three years. Preliminary individual adjuvant chemotherapy based on mRNA expression of drug-resistance gene is available for the treatment of recurrent malignant meningioma.

Combination effects of intravenous hyperalimentation (IVH) and chemotherapy were studied in rats with meningeal carcinomatosis. Sprague-Dawley rats were inoculated intracisternally with 1 X 10(4) Walker 256 carcinosarcoma cells. Animals were divided into five groups of 10 to 12 animals per group: 1) no treatment; 2) cyclophosphamide 30 mg/kg i.v. at 5 days after tumor inoculation (Day 5); 3) IVH (Day 5 to Day 10); 4) cyclophosphamide (Day 5) and IVH (Day 5 to Day 10); and 5) cyclophosphamide (Day 5) and IVH (Day 10 to Day 15). The group of IVH alone reduced survival time significantly (p less than 0.001) compared with no treatment group. Cyclophosphamide alone increased survival time significantly (p less than 0.001) in comparison with no treatment group. Combination of cyclophosphamide (Day 5) and IVH (Day 5 to Day 10) did not prolong survival time compared with cyclophosphamide alone. However, IVH (Day 10 to 15) in combination with cyclophosphamide (Day 5) prolonged survival time significantly (p less than 0.001) in comparison with cyclophosphamide alone. Mean body weight was reduced maximally at 5 to 10 days after cyclophosphamide injection. However, no reduction of body weight was noted while animals were on IVH. The present data appears to indicate that IVH may reduce the side effects of cyclophosphamide and may prolong the survival time.