Effect of turosteride, a 5 alpha-reductase inhibitor, on the Dunning R3327 rat prostatic carcinoma.
BACKGROUND
Turosteride (FCE 26073) is a new, potent, and selective 5 alpha-reductase inhibitor. We have investigated its effect on tumor growth, organ weight, and serum hormone levels in rats bearing the androgen sensitive Dunning R3327 prostatic carcinoma.


METHODS
Animals with tumor diameters of 0.5-1.5 cm were treated for 9 weeks with turosteride (50 and 200 mg/kg/day, 6 days a week, orally), flutamide (25 mg/kg/day, 6 days a week, orally), and leuprolide (300 micrograms/rat, every 3 weeks, subcutaneously) or they were castrated.


RESULTS
Turosteride was ineffective at the dose of 50 mg/kg/day, whereas at 200 mg/kg/ day it significantly decreased tumor growth by 45%. Flutamide and leuprolide were highly effective in reducing tumor growth (70 and 77%), although their effect was slightly lower than that of castration (85%). A significant reduction of ventral prostate weight occurred in rats treated with turosteride at 50 and 200 mg/kg/day (53% and 60%). In contrast to leuprolide and castration, the inhibitory effect of turosteride on tumor growth and prostate weight was not associated to any decrease in serum testosterone.


CONCLUSIONS
Turosteride has antitumor activity on Dunning prostatic tumor growth and its role in prostatic cancer treatment is worthy of further investigation.
Zaccheo
T
T
Department of Endocrinology, R&D Oncology, Pharmacia, Nerviano (MI), Italy.
Giudici
D
D
di Salle
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E
D058891:5-alpha Reductase Inhibitors; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000735:Androstenedione / Q000097:blood; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D013196:Dihydrotestosterone / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D018120:Finasteride / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005485:Flutamide / Q000008:administration & dosage / Q000494:pharmacology; D016729:Leuprolide / Q000008:administration & dosage / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010903:Pituitary Gland, Anterior / Q000187:drug effects; D011467:Prostate / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D012669:Seminal Vesicles / Q000187:drug effects; D013737:Testis / Q000187:drug effects; D013739:Testosterone / Q000097:blood
D058891:5-alpha Reductase Inhibitors; D018931:Antineoplastic Agents, Hormonal; D004791:Enzyme Inhibitors; D013196:Dihydrotestosterone; D013739:Testosterone; D000735:Androstenedione; D018120:Finasteride; D005485:Flutamide; D007986:Luteinizing Hormone; D016729:Leuprolide; C084634:turosteride