INHIBITION OF GROWTH AND APPEARANCE OF ESTROGEN-DEPENDENT RAT MAMMARY-TUMORS BY 10-PROPARGYLESTR-4-ENE-3,17-DIONE, AN AROMATASE INHIBITOR

The aromatase inhibitor 10-propargylestr-4-ene-3,17-dione (PED) has be en evaluated in vivo as an anticancer agent. Prolonged administration of PED to rats bearing dimethylbenzanthracene-induced mammary tumors r esulted in significant regression of hormone-responsive tumors within several days. Greater than 50% regression was generally observed after 14 days of treatment, irrespective of dose (1, 5, or 50 mg/kg body we ight/day). In addition to tumor regression, a significantly increased incidence in tumor stasis was observed over the course of PED treatmen t. While all doses of PED examined were equipotent for both tumor regr ession and stasis, a dose-dependent inhibition of new tumor formation was observed in PED-treated rats. In control animals an average of 1.2 new tumors was observed during the experimental period; in contrast, averages of 0.5 tumors appeared in animals receiving 1 mg PED/kg body weight/day, 0.1 tumors at 5 mg/kg, and at 50 mg of PED/kg body weight/ day, no new tumors occurred during the time PED was administered. The effects of PED on both regression of existing tumors and appearance of new tumors were reversed by co-administration of estradiol. Thus, PED impairs estrogen-dependent mammary tumor growth, resulting in cessati on of new growth and regression of responsive tumors.