EFFECT OF ZINDOXIFENE ON EXPERIMENTAL PROSTATIC TUMORS 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 antineoplastic 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.