[meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]- dichloroplatinum(II), a new drug not only parenterally but also orally active in the therapy of breast and prostate cancer

Abstract

The platinum complex [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)- ethylenediamine]dichloroplatinum(II),K, was tested for its antitumor activity on hormone-sensitive tumor models under peroral administration. The resorption from the gastrointestinal tract was proved by determining the estrogenic effect of K in a dose/activity study using the immature-mouse uterine weight test. In comparison to the subcutaneous injection, a tenfold peroral dose was administered to achieve identical effects. By peroral treatment of the hormone-sensitive MXT(M3.2) mammary carcinoma of the mouse with K an almost complete inhibition of the tumor growth was obtained. This effect was superior to that of subcutaneously applied cisplatin and significantly better than that obtained by perorally administered ligand L at an equimolar dose, indicating that the antitumor effect is caused by the intact complex K and not by the liberated ligand L. The strong antitumor activity of perorally applied K was also demonstrated on the hormone-sensitive Noble Nb-R prostatic carcinoma of the rat. Histological examinations showed that the platinum complex K did not cause cisplatin-like kidney damage or irritations of gastric or intestinal mucosa when given perorally.