Mifepristone. Auxiliary therapeutic use in cancer and related disorders.

OBJECTIVE: To evaluate the efficacy of mifepristone, a potent antagonist of progesterone and glucorticoids, in the management of cancer and disorders related to reproduction. STUDY DESIGN: Reports describing clinical trials of mifepristone treatment of leiomyoma, breast cancer, endometriosis and meningioma were reviewed. Mifepristone is a potent antagonist of progesterone and glucocorticoids. It is an effective contraceptive and abortifacient and in addition has been used in the management of diseases associated with pregnancy and adrenal cortical function. Results of the clinical trials show that it has beneficial and palliative value in some cases. Mifepristone may be used as an adjuvant therapeutic agent in cases of unresectable meningioma and leiomyoma that are refractory to chemotherapy, endocrine treatment or irradiation. In extensive endometriosis, mifepristone is indicated for intractable pain, although its effect on the lesions will be minimal. In the management of unresectable and metastatic breast cancer, mifepristone may be considered after a course of chemotherapy and/or irradiation and only in combination with another agent. In Cushing's syndrome mifepristone may be used to treat the undesirable sequelae of excessive cortisol production-e.g., psychosis. It will have minimal or no effect on the lesions of the adrenal or pituitary. The adverse effects of the long-term use of mifepristone are slight to moderate and reflect antiglucocorticoid effects. During treatment with mifepristone one should be aware of the possibility that the patient will develop Addisonian-like syndrome in the face of elevated blood ACTH and cortisol levels. RESULTS: Leiomyoma treated with 25 or 50 mg/d of mifepristone underwent a 25-49% reduction in tumor size. Treatment of endometriosis with a daily dose of 50 or 100 mg of mifepristone alleviated pelvic pain and uterine cramps and induced about 55% regression of the lesions. Treatment of metastatic breast cancer with 200 or 400 mg/d of mifepristone resulted in a partial response. Unresectable meningioma treated with 200 or 400 mg/d of mifepristone produced objective improvement in about 25% of subjects. CONCLUSION: Mifepristone is beneficial as adjuvant treatment in the management of unresectable, hormone-dependent tumors and disorders of the female reproductive system that are refractory to chemotherapy and irradiation.