[meso-1,2-Bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]sulfato-platinum(II) — Pharmacokinetic Studies

Abstract

The maximally attainable level of the non‐plasma protein bound fraction of a single 10.0 μmol/kg i.p. dose of [meso‐1,2‐bis(2,6‐di‐chloro‐4‐hydroxyphenyl)ethylenediamine]sulfatoplatinum(II), a drug active on the murine, hormone‐sensitive MXT‐M‐3.2 breast cancer, lies markedly below the concentration causing a significant cytotoxic effect on a cell line derived from this tumor. This result confirms our opinion that the strong in vivo activity of this drug on hormone‐sensitive breast cancers is mediated by its estrogenic potency by analogy with high dosed steroidal and non‐steroidal estrogens. A specific cytotoxic effect utilizing the estrogen receptor as carrier, as formerly postulated, is unlikely.

Does [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]-dichloroplatinum (II) Act on the Hormone-Sensitive, Murine Breast Cancer as a Biological Response Modifier? Part II. Studies on the Influence of [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) on the Specific Immune Defense in MXT-M-3,2 Breast Cancer Bearing Mice

“…Antitumor activity of meso-1-PtCl2, DES, E2, cDDP and ovariectomy on the hormone-sensitive MXT-M-3.2 mammary carcinoma in NMRI (nu/nu) mice, age 10 weeks. of action, which is based on their hormonal potency [1,2] . Indications that estrogens can modify the immune response in patients [5,[11][12][13][14][16][17][18][19] induced us to examine, if meso-1-PtCl 2 brings about its anti-breast cancer activity in rodents by enhancement of the body defense.…”

“…We have shown that the MXT-M-3,2 breast cancer implanted into female B6D2F 1 mice accelerates the growth of an identical second tumor and that this process is reversed to an inhibition by meso-1-PtCl 2 by virtue of its estrogenic potency [1,2,20] . We have supposed that the anti-breast cancer effect of meso-1-PtCl 2 and also of other estrogenic compounds (compare ref.…”

“…arachidis, 3 times weekly, sc, begin of therapy 10 d before tumor transplantation * Significant against the intact control group (p<0.01) ** Significant against the CyA-group (p<0.01) In the studies on the mode of action of meso-1-PtCl 2 performed on MXT-MC bearing NMRI (nu/nu) mice we used the estrogens E2 and DES for comparison. These drugs are supposed to act by the same mechanism as meso-1-PtCl 2 on hormone-sensitive breast cancers [1,2] . The sensitivity of the MXT-M-3,2 breast cancer implanted into NMRI (nu/nu) mice (age 10 weeks) against cytostatics and endocrine therapeutic measures was examined by its response to cDDP and ovariectomy, respectively.…”

“…Introduction 1) In preceeding publications [1,2] we have reported that the marked inhibitory effects of [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) (meso-1-PtCl 2 ) on ER + rodent breast cancers are not due to the capability of stopping the DNA replication (main mechanism of the anti-tumor activity of cisplatin and derived platinum complexes), but to its estrogenic potency. This concept of the mode of action resulted from a comparative therapeutic study with meso-1-PtCl 2 and the non-steroidal estrogen DES on the ER + murine MXT-M-3,2 breast cancer implanted into ovariectomized mice, in which these drugs yielded identical courses of the dose-activity-curves, i.e.…”

Does [meso-1,2-Bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]-dichloro-platinum(II) Act as an Immune Response Modifier? Part III: Progressively Growing MXT-M-3,2 Breast Cancer Stimulates the Proliferation of Phagocytes in B6D2F1 Mice

“…The technique of the animal experiments is thoroughly described in the preceding publications [1][2][3] .…”