Medical therapies for meningiomas

Abstract

Meningiomas are the most common primary brain tumor in adults. Although the majority of these tumors can be effectively treated with surgery and radiation therapy, an important subset of patients have inoperable tumors, or develop recurrent disease after surgery and radiotherapy, and require some form of medical therapy. There are increasing numbers of studies evaluating various medical therapies but the results remain disappointing. Chemotherapies and hormonal therapies have been generally ineffective, although somatostatin analogues may have therapeutic potential. There is also increasing interest in targeted molecular therapies. Agents inhibiting platelet derived growth factor receptors and epidermal growth factor receptors have shown little efficacy, but molecular agents inhibiting vascular endothelial growth factor receptors appear to have some promise. As with other tumors, advances in the medical therapies for meningiomas will require improved understanding of the molecular pathogenesis of these tumors, more predictive preclinical models, and efficient mechanisms for conducting clinical trials, given the small population of eligible patients.

Management of Malignant Meningiomas

“…The data has been controversial, with meningiomas being more frequent among women who had multiple pregnancies and among patients with history of breast cancer. However, early menarche and late menopause have not increased the risk of developing meningioma (Grunberg et al, 1991;Wen et al, 2010). Progesterone and androgen receptors are expressed on approximately two thirds of meningiomas and estrogen receptors are expressed on approximately 10% (Wen et al, 2009).…”

“…Mifepristone's lack of efficacy may be explained in part by the loss of progesterone receptor expression in meningiomas with increased proliferation index and histologic grade. This is relevant because these advanced tumors are the type most likely to be enrolled into clinical studies (Grunberg et al, 2006;Wen et al, 2010).…”

“…Somatostatin receptors are expressed in nearly 90% of meningiomas (Norden et al, 2011;Wen et al, 2010).…”

“…Epidermal growth factor receptor (EGFR) is overexpressed in over 60% of meningiomas (Johnson & Toms, 2005;Wen et al, 2010). EGF and transforming growth factor (TGF ) activate these receptors stimulating meningioma cell proliferation in vitro (Johnson & Toms, 2005).…”

Radiocirurgia e radioterapia estereotática no tratamento de meningeomas sintomáticos do seio cavernoso

“…Sabe-se que 60% a 70% dos doentes com meningeoma expressam receptores de progesterona e de andrógenos e 10%, receptores estrogênicos (Wen et al, 2010). Entretanto, a hormonioterapia não se revelou eficaz no controle dos meningeomas, apesar de opiniões contrárias (Pravdenkova et al, 2006 (Markwalder et al, 1985), a gestrinona (antiestrogênica e antiprogestínica), a buserelin (superagonista do LHRH), o octreótide análogo da somatostatina, do inibidor da proliferação celular in vitro das células do meningeoma (García-Luna et al, 1993), e a bromocriptina, agonista dopaminérgico, sem que melhora consistente ou regressão tumoral fosse observada (Goodwin et al, 1993;da Motta;da Motta, 1995).…”