The antitumor effects of cis[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)]
platinum(II) (SM-11355) were evaluated in a rat hepatic
tumor model, and were compared with those of
cisplatin (CDDP). A novel slowly-growing rat hepatic
tumor model was established by the successive
transplantation of rat AH109A
tumor into the liver. The drugs, which were suspended in
Lipiodol, were administered into the proper hepatic artery of
tumor-bearing rats.
Tumor growth was suppressed in the group that received
SM-11355 suspended in
Lipiodol (
SM-11355/
Lipiodol). Mean
tumor growth rates in the groups administered 20 microl of
Lipiodol containing 0, 0.02, 0.04, 0.1, 0.2, or 0.4 mg of
SM-11355 were 244, 86, 110, 81, 51, and 40%, respectively, 1 week
after treatment. Those in the groups administered 20 microl of
Lipiodol containing 0.1, 0.2, or 0.4 mg of CDDP were 240, 110, and 45%, respectively. In the groups administered 0.2 and 0.4 mg of
SM-11355 or 0.4 mg of CDDP, massive
necrosis was observed in the
tumor tissue 1 week after
drug administration, and the
tumors disappeared 4 weeks after
drug administration.
Serum glutamic-oxaloacetic transaminase (GOT) and
glutamic-pyruvic transaminase (GPT) levels were measured as markers of liver damage one day after the
drug was administered into the hepatic artery of rats. The minimum toxic dose, which raised serum GOT and GPT levels significantly compared with
Lipiodol alone, was 0.2 mg for
SM-11355/
Lipiodol and 0.1 mg for CDDP/
Lipiodol, respectively. The results demonstrated that
SM-11355/
Lipiodol exerted antitumor activity at a dose that showed no hepatic toxicity in the rat model, but CDDP/
Lipiodol did not.