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Aromatase inhibitors in human breast cancer

Published online by Cambridge University Press:  05 December 2011

R. C. Coombes ,
R. C. Stein  and
M. Dowsett
R. C. Coombes
Affiliation:
Clinical Oncology Unit, St George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, U.K.
R. C. Stein
Affiliation:
Clinical Oncology Unit, St George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, U.K.
M. Dowsett
Affiliation:
Department of Endocrinology, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, U.K.
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Synopsis

The results of a phase I/II study in advanced breast cancer in postmenopausal women of the aromatase inhibitors 4-hydroxyandrostenedione (40HA), miconazole and CGS16949A are described. 40HA, a steroidal compound which is an irreversible inhibitor of aromatase, has been administered to 131 patients by weekly (500 mg) or fortnightly (250 mg) i.m. injections, and daily (500 mg) by mouth. The overall response rate (complete regression (CR) and partial regression (PR)) was 33%; all three dose schedules had similar clinical efficacy. Oestradiol levels were suppressed to a mean of 37–45% of pretreatment values with oral and with weekly i.m. 40HA; suppression was marginally suboptimal with 250 mg i.m. fortnightly. 40HA was well tolerated, especially when administered by fortnightly injections; this dose schedule is to be preferred to weekly injections.

Significant oestradiol suppression and clinical responses did not occur with the imidazole antifungal, miconazole, which was administered to twenty-two patients at doses of 500–1000 mg daily. The non-steroidal aromatase inhibitor, CGS16949A, induced comparable oestradiol suppression to 40HA at doses of 0.6–4 mg daily; 0.6 mg daily appears to be suboptimal. Five of thirty-one patients treated had objective responses, and disease stabilised for at least six months in nine patients. Some suppression of aldosterone occurred with doses of 2 and 4 mg daily, but clinical toxicity of the compound was minor.

Type
Research Article
Information
Proceedings of the Royal Society of Edinburgh, Section B: Biological Sciences , Volume 95: Oestrogen and the Human Breast , 1989 , pp. 283 - 291
Copyright
Copyright © Royal Society of Edinburgh 1989

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