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Onapristone, a progesterone receptor antagonist, as first-line therapy in primary breast cancer
J F Robertson1, P C Willsher, L Winterbottom
1Professorial Unit of Surgery, City Hospital, Nottingham, U.K. john.robertson@nottingham.ac.uk
Abstract:
The progesterone receptor antagonist, Onapristone, is an effective endocrine agent in experimental breast cancer models. This study aimed to investigate this agent as first-line endocrine therapy in patients with breast cancer. However, owing to the recognition in this and other clinical studies that 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 were elderly, unfit patients with primary breast cancer (n = 7) received Onapristone 100 mg/day. Seventeen of the 19 tumours expressed oestrogen receptors (ER) whilst 12 of the 18 tumours tested expressed progesterone receptors (PgR). Tumour remission was categorised by International Union Against Cancer criteria. One patient was withdrawn after 4.5 months while her disease was static. Of the remaining 18 patients, 10 (56%) showed a partial response and 2 (11%) durable static disease (> or = 6 months), giving an overall tumour remission rate of 67%. The median duration of remission was 70 weeks. Transient liver function test abnormalities developed in a number of patients, mainly during the first 6 weeks of treatment. In conclusion Onapristone can induce tumour responses in human breast cancer.
Insights
Onapristone, a progesterone receptor antagonist, showed a 67% tumor remission rate in breast cancer patients. Despite transient liver abnormalities, it effectively induces tumor responses in human breast cancer.
Area of Science:
- Oncology
- Pharmacology
Background:
- Onapristone is a progesterone receptor antagonist with demonstrated efficacy in experimental breast cancer models.
- Clinical development was halted due to observed liver function test abnormalities in some patients.
Purpose of the Study:
- To evaluate Onapristone as a first-line endocrine therapy for patients with breast cancer.
- To assess tumor response and safety profile of Onapristone in a clinical setting.
Main Methods:
- Nineteen patients with locally advanced or primary breast cancer received Onapristone 100 mg/day.
- Tumor remission was assessed using International Union Against Cancer criteria.
- Tumor receptor status (oestrogen and progesterone) was evaluated.
Main Results:
- An overall tumor remission rate of 67% was observed (10 partial responses, 2 durable static disease).
- The median duration of remission was 70 weeks.
- Transient liver function test abnormalities occurred, primarily within the first 6 weeks of treatment.
Conclusions:
- Onapristone demonstrated the ability to induce tumor responses in human breast cancer.
- The drug's potential as an endocrine therapy warrants consideration, balanced against its safety profile.