Tumor inhibition by metallocenes: Activity against leukemias and detection of the systemic effect

The antitumor activity of two representatives of the metallocene dihalides, titanocene dichloride (TDC) and vanadocene dichloride (VDC), is investigated by the use of various experimental tumor systems. Against the lymphoid leukemia L1210 and the lymphocytic leukemia P388, TDC and VDC induce significant increases of life span corresponding to T/C values which exceed 125%. On treating advanced stages of fluid EAT with single doses, TDC causes, when applied within 5 days after transplantation, the survival of 80–100% of the treated animals, whereas VDC cures progressed stages of fluid EAT to a much minor extent. Investigations using a solid EAT subcutaneously growing in the nuchal region show that the intraperitoneally applied metallocene dihalides are able to inhibit tumor growth in a highly significant manner so that the minimum tumor sizes attain 14% (TDC) or 31% (VDC) of the control values. This result indicates that the antiproliferative activity of the metallocene dihalides is based on a systemic effect.