Effect of zindoxifene on experimental prostatic tumours of the rat

The anti-oestrogen zindoxifene was originally developed as a drug for the treatment of hormone-dependent mammary carcinomas. Experiments with rats bearing androgen-dependent prostatic tumours revealed anti-neoplastic activity of zindoxifene on these tumours also. Therefore, the inhibitory effect of this drug was studied in various prostatic tumour models in comparison to the anti-oestrogen tamoxifen and to castration. The growth of the hormone-dependent Dunning R3327 H tumour was strongly inhibited by zindoxifene (4 mg/kg), which was more effective than tamoxifen (43% T/C vs 87% T/C, the ratios of tumour weights in control and drug-treated rats). Zindoxifene was able to delay the relapse of these tumours by 7 weeks in comparison to castration. The experiments with Noble Nb-R prostatic tumours showed that administration of zindoxifene (5 mg) is superior to castration (5% T/C vs 52% T/C). The growth of tumours in castrated rats was completely inhibited by administration of zindoxifene. Therefore a peripheral mode of action has to be assumed.