Antitumor activity of a new platinum complex, oxalato (trans-l-1,2-diaminocyclohexane)platinum (II): new experimental...

Antitumor activity of a new platinum complex, oxalato (trans-l-1,2-diaminocyclohexane) platinum (II) (l-OHP), was studied. This water-soluble platinum complex showed a more prominent life-prolonging effect on a mouse leukemia L1210 than cisplatin (DDP). By an intermittent treatment schedule cured mice were observed at the optimal dose. In addition, a subline of L1210 having a 40-fold resistance to DDP (L1210/DDP) showed lack of cross-resistance to l-OHP both in vivo and in vitro. Especially in vivo l-OHP was more active against L1210/DDP than against the original L1210, and all mice were cured at doses of 6.25 and 3.12 mg/kg. l-OHP was also effective against several mouse tumors such as P388 leukemia, B16 melanoma, Lewis lung carcinoma, colon 26 and colon 38 adenocarcinomas, and M5076 fibrosarcoma, though its antitumor spectrum was somewhat different from that of DDP. The synthesis of both DNA and RNA in L1210 cells was inhibited by about 50% with exposure to 10 microM of l-OHP for 1 h, followed by postincubation in drug-free medium for 6-24 h, while only the inhibition of DNA synthesis was observed by DDP in the same experiment. If severe toxicity is not observed in preclinical study, l-OHP expected to be a new clinically active Pt complex.