Chronic suppressive therapy with calcium channel antagonists for refractory meningiomas

Abstract

✓In this article, the authors review the research supporting the use of calcium channel antagonists (CCAs) in the treatment of recurrent or unresectable meningiomas. Calcium channel antagonists (for example, diltiazem and verapamil) are known to augment the effects of chemotherapy drugs (for example, vincristine) in multiple cancers. Although it was initially thought that this occurred by interference with calcium-dependent secondary messenger systems, it appears that other mechanisms account for this effect. The authors' initial work in this field was based on the then-emerging data that meningiomas are receptor positive for growth factor receptors (for example, platelet-derived growth factor [PDGF]), which are known to trigger calcium-dependent secondary messenger pathways. In fact, they were able to show that CCAs block the growth stimulatory effects of multiple growth factors, including PDGF, in vitro and augment the growth inhibitory effects of hydroxyurea and RU486 (mifepristone). The authors have shown similar in vivo growth inhibition by these agents. In addition, diltiazem- and verapamil-treated meningiomas are less vascular and smaller, with decreased cell proliferation and increased apoptosis. The use of CCAs is attractive as an adjunct treatment for unresectable or recurrent meningiomas because they are safe drugs with well-known side effect profiles that lend themselves to long-term chronic therapy.