Antitumor activity of the aromatase inhibitor FCE 24928 on DMBA-induced mammary tumors in ovariectomized rats treated with testosterone.

The antitumor activity of the irreversible aromatase inhibitor FCE 24928 (4-aminoandrosta-1,4,6-triene-3,17-dione) was studied in ovariectomized and testosterone propionate (TP)-treated rats bearing 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumors. This experimental condition was used as a model of postmenopausal breast cancer. TP was given s.c. three times per week for 4 weeks at a dose of 20 mg/kg per day, a treatment that is effective in maintaining tumor growth in ovariectomized rats (89% growing tumors). FCE 24928 given s.c. twice daily 6 days/week for 4 weeks at doses of 10 and 30 mg/kg per day inhibited the tumor growth-promoting effect of TP as shown by 81% and 80% tumor-regression rates. When FCE 24928 was given at various dose levels either s.c. (3, 10, and 30 mg/kg daily) or orally (10, 30, and 100 mg/kg per day), tumor regressions were observed at all doses, amounting to 63%-93% and 63%-72%, respectively. In addition, FCE 24928 given alone (30 mg/kg daily s.c.) to ovariectomized rats did not affect ovariectomy-induced tumor regression. In conclusion, following both s.c. and oral administration, FCE 24928 was effective against DMBA-induced mammary tumors in ovariectomized TP-treated rats, a postmenopausal mammary tumor model.