In vitro and animal studies with antiprogestins

This paper examines the potential of progesterone antagonists for treating hormone dependent breast cancer, as judged from experimental studies. The original lead compound, Ru (38)486 (Mifepristone), was intended originally to be an antiglucocorticoid. It is apparent that there are pregnancy-related indications for this compound. For the much newer more specific compounds there are several tumour indications. The growth inhibitory efficacy of a prosgesterone antagonist was compared with different endocrine treatment regimens in the MNU-induced mammary carcinoma model. Long-term treatment with onapristone achieved the most effective inhibition of tumour growth. In a second-line treatment regimen, after 3 weeks pretreatment with tamoxifen, the effectiveness of onapristone on tumour growth was equal with the efficacy of medroxyprogesterone acetate. The efficacy of a combined treatment of a progesterone antagonist and a ‘pureʹ antioestrogen (ICI 164.384) was investigated in the MXT mouse mammary carcinoma. The combined treatment was more effective than oophorectomy. Tumour inhibition induced by progesterone antagonists appears to be associated with the induction of apoptosis.