A New Aromatase Inhibitor, in Postmenopausal Women
(CANCERRESEARCH52, 5933-5939, November1, 1992J Phase I and Endocrine Study of Exemestane (FCE 24304), a New Aromatase Inhibitor, in Postmenopausal Women T. R. Jeffry Evans,' Enrico Di Salle, Giorgio Ornati, Mercedes Lassus, Margherita Strolin Benedetti, Eio Pianezzola, and R. Charles Coombes Department ofMedical OncoIoij@,St. Geoa@ge'sHospital Medical School, Creamer Terrace, London SWI7 ORE, England fT. R. I. E.J; Departments of Oncology IE. D. S., G. 0., M. Li and Pharmacokinetics and Metabolism [M. S. B., E. P.J, Farmitalia Carlo Erba, Via Carlo Imbonati, Milan, Italy; and Department of Medical Oncology, Charing Cross Hospital, FuThoin Palace Roa@ London W6 8RF, England (R. C. C.] ABSTRACT aminoglutethimide and fadrozole (CGS 16949A) (7). Objective tumor regression occurred in approximately 21% of patients Aromatase inhibitors are a useful therapeutic option in the manage treated with 4}IAI@@,2witha low incidence of adverse effects; ment of endocrine-dependent advanced breast cancer. A single-dose 4.5% of patients were withdrawn from treatment because of administration of exemestane (FCE 24304; 6-methylenandrosta-l,4-dl ene-3,17-dione), a new Irreversible aromatase inhibitor, was investi side effects. However, 4HAD undergoes extensive metabolism gated in 29 healthy postmenopausal female volunteers. The compound, in the liver to form the inactive glucuronide (8) and conse given at p.o. doses ofO.5, 5, 12.5, 25, 50, 200, 400, and 800 mg(n = 3—4), quently it is recommended that it is given i.m. rather than p.o. was found to be a well tolerated, potent, long-lasting, and specific in The use of aminoglutethimide as an aromatase inhibitor is re hibitor of estrogen biosynthesis.
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