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. 1993 Dec;119(12):707–716. doi: 10.1007/BF01195341

[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

Thilo Spruß 1,✉, Sabine Schertl 2, Martin R Schneider 1, Ronald Gust 1, Kurt Bauer 2, Helmut Schönenberger 1
PMCID: PMC12200136  PMID: 8408183

Abstract

The platinum complex [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)-ethylenediamine]dichloroplatinum(II), K, was tested for its antitumor activity on hormonesensitive 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.

Key words: Platinum complex, Peroral administration, Estrogenic activity, Antitumor activity, MXT(M3.2) mouse mammary tumor, Noble Nb-R rat prostatic tumor, Toxicity

Abbreviations

DMBA

dimethylbenz[a]anthracene

ER

estrogen receptor

K

complex

[meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl

(ethylenediamine]dichloroplatinum(II)

L

ligand:meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine

LM

1∶1 mixture (v/v) of polyethyleneglycol 400 and 1.8% NaCl

PEG

polyethylene glycol

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