Role of antiprogestational therapy for meningiomas

Epidemiological evidence, including the greater incidence of female patients, a positive association with pregnancy, and a positive association with breast cancer suggested a role for female sex hormones (and hormonal modulation) in regulating the growth of meningioma. The detection of hormone receptors on meningioma specimens provided a mechanism for this effect. However, unlike breast cancer, progesterone receptors (not oestrogen receptors) predominate in meningioma. Clinical trials with anti-oestrogens have shown little effect while trials with progesterone agonists have shown no effect or possible stimulation of meningioma growth. Three trials have now indicated an inhibitory activity of the antiprogestational agent mifepristone. In the largest of these trials, 28 patients received daily oral mifepristone for up to 62 months with a suggestion of response in eight patients. Long-term therapy has been well tolerated. Adverse events include fatigue, hot flushes, gynaecomastia/breast tenderness, skin rash, cessation of menses and decrease in libido. Increases in cortisol and thyroid-stimulating hormone are the most striking endocrine changes. A randomized double-blind placebo-controlled phase III trial is underway to confirm the activity of mifepristone in unresectable meningioma.