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.
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.
D000818:Animals; D002021:Buffers; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006863:Hydrogen-Ion Concentration; D051379:Mice; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D014025:Titanium / Q000009:adverse effects / Q000627:therapeutic use*
D002021:Buffers; D009942:Organometallic Compounds; D014025:Titanium; C020528:titanocene dichloride