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. 1980;97(1):31-9.
doi: 10.1007/BF00411276.

Tumor inhibition by metallocenes: antitumor activity of titanocene dihalides (C5H5)2TiX2 (X=F, Cl, Br, I, NCS) and their application in buffered solutions as a method for suppressing drug-induced side effects

P Köpf-Maier, B Hesse, R Voigtländer, H Köpf

Tumor inhibition by metallocenes: antitumor activity of titanocene dihalides (C5H5)2TiX2 (X=F, Cl, Br, I, NCS) and their application in buffered solutions as a method for suppressing drug-induced side effects

P Köpf-Maier et al. J Cancer Res Clin Oncol. 1980.

Abstract
in English, German

The antitumor activity of titanocene dihalides (C5H5)2TiX2 with X=F, Cl, Br, I, NCS is investigated against Ehrlich ascites tumor in CF 1 mice. Varying doses of the compounds are applied as single i.p. injections 24 h p.t.t. both in non-buffered (pH 1.4-3.9) and buffered (pH 4.2-5.9) solutions or suspensions, all of the substances achieving in optimum doses cure rates of 100% on day 120 p.t.t. This corresponds to I.L.S. values of 600-750% referred to the untreated controls. Some drug-induced side effects, especially the appearance of postperitonitic symptoms several weeks after i.p. application of higher doses of titanocene dihalides, are strikingly reduced by pH elevation in the injected drug solutions.

Die tumorhemmende Wirksamkeit von Titanocen-dihalogeniden (C5H5)2TiX2 mit X=F, Cl, Br, J, NCS wird an Ehrlich-Aszites-Tumor-tragenden CF 1-Mäusen untersucht. Verschiedene Dosen der Substanzen werden 24 h p.t.t. als einmalige i.p.-Injektionen sowohl in ungepufferten (pH 1.4–3.9) als auch in gepufferten (pH 4.2–5.9) Lösungen bzw. Suspensionen appliziert. Mit allen Verbindungen werden in optimaler Dosis Heilungsraten von 100% am 120. Tag p.t.t. erreicht. Dies entspricht Verlängerungen der mittleren Überlebensdauer (I.L.S.-Werte) um 600–750% gegenüber den unbehandelten Kontrolltieren. Einige substanzbedingte Nebenwirkungen, insbesondere das Auftreten postperitonitischer Symptome mehrere Wochen nach i.p.-Applikation höherer Dosen der Titanocen-dihalogenide, werden durch pH-Erhöhung in den Injektionslösungen deutlich zurückgedrängt.

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