Effect of early treatment of prostate cancer with the 5alpha-reductase inhibitor turosteride in Dunning R3327 prostatic carcinoma in rats.
BACKGROUND
Turosteride, a selective 5alpha-reductase inhibitor, was reported to be effective in inhibiting the growth of established tumors in the Dunning R3327 rat prostatic carcinoma model. We evaluated the preventive effect of turosteride when administered during the latency period in this prostatic tumor model.


METHODS
Turosteride was given orally, 6 days a week for 10-15 weeks, starting at different times: 1) 5 weeks after tumor implantation, when tumors were not yet palpable, or 2) 1 day after tumor implantation. In each experiment, one group of animals was castrated on the first treatment day.


RESULTS
When treatment started 5 weeks after tumor implantation, neither turosteride (at 50 and 200 mg/kg/day) nor castration reduced tumor incidence (91-100%). Tumor growth was reduced in groups treated with the highest dose of turosteride and in castrated rats. When treatment started 1 day after tumor implantation, castration resulted in a 62% tumor incidence compared to 100% in controls, while turosteride at 200 mg/kg/day was not effective in reducing tumor incidence. However, as in the previous experiment, the compound was highly effective in reducing tumor growth.


CONCLUSIONS
The antitumor activity profile of turosteride seems not to be related to the timing of treatment. Given either 5 weeks or 1 day after tumor implantation, the compound did not reduce tumor take, while it maintained effective tumor growth-inhibiting activity in both cases.
Zaccheo
T
T
Laboratory of Experimental Endocrinology, Department of Oncology Research, Pharmacia and Upjohn, Nerviano, Italy. tiziana.zaccheo@eu.pnu.com
Giudici
D
D
di Salle
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E
D058891:5-alpha Reductase Inhibitors; D000284:Administration, Oral; D000818:Animals; D002460:Cell Line; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D018120:Finasteride / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000033:anatomy & histology / Q000187:drug effects / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D013997:Time Factors
D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D018120:Finasteride; C084634:turosteride