[Combination effect of flutamide and leuprorelin acetate on growth of Dunning R3327-H prostatic adenocarcinoma in rats].
Combined androgen blockade using a pure antiandrogen in association with a LHRH agonist or surgical castration is the most logical approach. This paper demonstrated that flutamide combined with leuprorelin acetate produced a significant reduction in the growth rate of Dunning R3327-H prostatic adenocarcinoma. Dunning R3327-H prostatic adenocarcinoma, provided by Dr. Norman H. Altmann (University of Miami, USA) was subcutaneously inoculated into the lateral region of male Copenhagen x Fischer F1 hybrid rat abdomen. The efficacy of the tumor growth rate was evaluated by measuring tumor size at 10 weeks after the inoculation. Flutamide was orally administered for 10 weeks and leuprorelin acetate was subcutaneously administered every 4 weeks. The effective dose of flutamide and leuprorelin acetate was determined in preliminary studies, and the following doses were used in the study; 15 mg/kg for flutamide, 0.1 mg/kg or 0.4 mg/kg for leuprorelin acetate. In combination of flutamide with leuprorelin acetate at 0.1 mg/kg and 0.4 mg/kg, the tumor inhibition was 94% and 97%, respectively. In addition, the weight of accessory sex organs coincided with the antitumor effect. Taking the above results into consideration, combined androgen blockade using flutamide and leuprorelin acetate may have some beneficial effect on prostatic cancer.
Tomura
A
A
R & D. Division, Pharmaceuticals Group, Nippon Kayaku Co., Ltd.
Kuroiwa
S
S
Okada
M
M
Abe
F
F
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D004334:Drug Administration Schedule; D005485:Flutamide / Q000008:administration & dosage / Q000494:pharmacology; D016729:Leuprolide / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051381:Rats
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D005485:Flutamide; D016729:Leuprolide