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  • Title: Use of the aromatase inhibitor 4-hydroxyandrostenedione in postmenopausal breast cancer: optimization of therapeutic dose and route.
    Author: Dowsett M, Goss PE, Powles TJ, Hutchinson G, Brodie AM, Jeffcoate SL, Coombes RC.
    Journal: Cancer Res; 1987 Apr 01; 47(7):1957-61. PubMed ID: 3815384.
    Abstract:
    4-Hydroxyandrostenedione (4-OHA) is a potent inhibitor of estrogen production by aromatase and causes suppression of plasma estradiol levels and disease regression in postmenopausal breast cancer patients. Groups of patients were given p.o. or parenteral 4-OHA, and plasma estradiol and 4-OHA levels were measured to enable the delineation of the minimal effective dose and optimal therapeutic regimen. A single injection of 500 mg i.m. suppressed estradiol levels to a mean 36.3 +/- 3.3% (SE) (n = 14) of base line after 4 to 7 days and maintained this suppression in six of seven patients for greater than 14 days. The half-life of 4-OHA was approximately 8 days, and when the level had fallen to less than 3 ng/ml, estradiol levels began to rise. Similar suppression was achieved by a single i.m. injection of 125 mg of 4-OHA and by 500 mg of 4-OHA p.o. daily after 1 wk, but escape from suppression was more rapid.
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