Antitumoral effects of R 75251 on the growth of transplantable R3327 prostatic adenocarcinoma in rats.

The antitumoral activity of a novel imidazole derivative, R 75,251, has been studied in the androgen-dependent R3327G Dunning prostate adenocarcinoma grafted subcutaneously in syngeneic rats. Dietary application resulting approximately in dose levels of 80, 120, and 160 mg/kg reduced tumor weight by 66, 81, and 79%, respectively. This effect was not significantly different from that measured after castration (-82%). In intact animals, however, serum testosterone levels were almost not affected by R 75,251 treatment while LH levels rose two- to threefold. In castrated rats a tenfold increase in LH was observed. Moreover, prostate and seminal vesicles weights decreased much less after R 75,251 treatment than after castration. In castrated animals, treatment with R 75,251 induced a slight, non-significant reduction in tumor weight (-36%) compared with castration alone. In castrated animals, tumor growth was restored by exogenous administration of testosterone. In such animals R 75,251 also significantly reduced tumor weight by 57%. Similar results were obtained with Dunning R3327G prostate adenocarcinoma grafted beneath the renal capsule in male syngeneic rats receiving twice daily orally by gavage a dose of 80 mg/kg of R 75,251. These data suggest that R 75,251 exerts an antitumoral effect independent of its inhibition of androgen biosynthesis.