The enhanced therapeutic efficacy of intra-arterial cis-diamminedichloroplatinum (II) chemotherapy in combination with aortic clamping on metastatic hepatic tumors in the rat.
The efficacy of intrahepatic cis-diamminedichloroplatinum (II), cisplatin, administered via the hepatic artery in combination with concomitant clamping of the abdominal aorta beneath the diaphragm against metastatic liver tumors in rats was evaluated. When 2.5 or 5 mg/kg of cisplatin was injected intra-arterially (i.a.) over 5 min, the antitumor activities in the rats with aortic clamping, evaluated by the number of tumor nodules and survival days after treatment, were found to be superior to those in the rats without aortic clamping. Side effects, evaluated in terms of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase levels, changes in body weight, and the number of leukocytes, did not differ significantly among the rats with or without aortic clamping. The blood urea nitrogen levels observed in the rats with aortic clamping were lower than in those without aortic clamping. Immediately after the injection of cisplatin 5 mg/kg i.a., the platinum concentrations in the livers of rats with aortic clamping were approximately 2.1 times higher than in those without aortic clamping, and 1.4 times higher even 60 min after the injection. These increased platinum concentrations in the liver explain the enhanced antitumor activities of the rats given cisplatin with aortic clamping.
Nishioka
Y
Y
Second Department of Surgery, Tokyo Medical and Dental University, Japan.
D000818:Animals; D001012:Aorta, Abdominal; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003250:Constriction; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008102:Liver Circulation; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000556:secondary* / Q000628:therapy*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002945:Cisplatin