Antitumor activity of four polymer bound trans-1,2-diaminocyclohexaneplatinum(II)-4-carboxyphtalate complexes tested...

Four polymer bound Pt-complexes have been tested in in vivo and in in vitro systems. No substantial difference in effectivity against P388 leukemia in vivo was found when free trans-1,2-diaminocyclohexaneplatinum(II)-4-carboxyphtalate (TMA) was compared with the polymer bound complexes. The compound with the highest ID50 value in soft agar assay exhibited low effectivity in in vivo testing. Polymer bound Pt-complexes with faster release of the active molecule exhibited in in vivo and in soft agar assay slightly lower activity, when compared with suspension culture test system. Cross resistance of polymer bound complexes was investigated on three cell lines with induced drug resistance against different Pt-complexes. Cross resistance was found between TMA (free and polymer bound) and trans-1,2-diaminocyclohexaneplatinum(II)citrate (PEX) as well as trans-1,2-diaminocyclohexaneplatinum(II)glucarate (PTU) but there was no cross resistance between TMA and cis-diamminedichloroplatinum(II) (cis-DDP).