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.