Effect of early treatment of prostate cancer with the 5α-reductase inhibitor turosteride in Dunning R3327 prostatic carcinoma in rats

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Abstract
Turosteride, a selective 5α-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. 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. 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. 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. Prostate 35:237–242, 1998.