Onapristone, a progesterone receptor antagonist, as first-line therapy in primary breast cancer

The progesterone receptor antagonist, Onapristone, is an effective endocrin e agent in experimental breast cancer models. This study aimed to investiga te this agent as first-line endocrine therapy in patients with breast cance r. However, owing to the recognition in this and other clinical studies tha t some patients on Onapristone developed Liver function test abnormalities, the development of this drug and recruitment to the study stopped in 1995. 19 patients either with locally advanced breast cancer (n = 12) or who wer e elderly, unfit patients with primary breast cancer (n = 7) received Onapr istone 100 mg/day. Seventeen of the 19 tumours expressed oestrogen receptor s (ER) whilst 12 of the 18 tumours tested expressed progesterone receptors (PgR). Tumour remission was categorised by International Union Against Canc er criteria. One patient was withdrawn after 4.5 months while her disease w as static. Of the remaining 18 patients, 10 (56%) showed a partial response and 2 (11%) durable static disease (greater than or equal to 6 months), gi ving an overall tumour remission rate of 67%. The median duration of remiss ion was 70 weeks. Transient liver function test abnormalities developed in a number of patients, mainly during the first 6 weeks of treatment. In conc lusion Onapristone can induce tumour responses in human breast cancer. (C) 1999 Elsevier Science Ltd. All rights reserved.