Effect of the irreversible aromatase inhibitor FCE 24304 on DMBA-induced mammary tumors in ovariectomized rats treated with testosterone.
The antitumor activity of the irreversible aromatase inhibitor FCE 24304 (6-methylenandrosta-1,4-diene-3,17-dione) was studied in ovariectomized, testosterone propionate (TP)-treated rats with 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumors that were used as a postmenopausal tumor model. When given s.c. at 20 mg/kg per day, 3 days a week for 4 weeks, TP was effective in maintaining tumor growth in ovariectomized rats (51% tumor regression in control animals vs 94% in ovariectomized rats). FCE 24304 given s.c. twice daily at 100 mg/kg per day, 6 days a week for 4 weeks, induced 96% regression, thus inhibiting the growth-promoting effect of TP. When the effect of various doses of FCE 24304 was evaluated, in comparison with a 52% tumor regression rate in control (ovariectomized, TP-treated) rats, tumor regressions amounted to 88% and 96% at s.c. FCE 24304 doses of 10 and 50 mg/kg per day, respectively, and to 76%, 88%, and 81% at oral doses of 10, 50, and 100 mg/kg per day, respectively. When FCE 24304 was given alone to ovariectomized rats, it did not affect ovariectomy-induced tumor regression (87% vs 94%). In conclusion, FCE 24304 was effective by both the s.c. and oral routes against DMBA-induced mammary tumors in ovariectomized TP-treated rats, a postmenopausal mammary tumor model.
Zaccheo
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R & D/Oncology, Farmitalia Carlo Erba, Erbamont Group, Milano, Italy.
Di Salle
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D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000730:Androstadienes / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000008:administration & dosage*
D000730:Androstadienes; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D013739:Testosterone; D015127:9,10-Dimethyl-1,2-benzanthracene; C056516:exemestane