Upper Hemibody Infusion of Cis-diamminedichloroplatinum (II) Followed by Systemic Antidote, Sodium Thiosulfate, for Lung Metastasis in Rats

Effects of a combination chemotherapy using cis-diamminedichloroplatinum (II) (DDP) and its antidote, sodium thiosulfate (STS), on metastatic lung tumour in rats were studied. Rats were given an upper hemibody infusion (UHI) of 15 mg/kg DDP immediately after occlusion of the abdominal aorta and i.v. administration of 1581 mg/kg STS (200-fold molar ratio to DDP) 10 min later. The aortic clamp was released at approximately 11 min after the beginning of UHI when a half volume of STS solution was infused. Antitumour and side effects in this group were compared with those in the respective control groups given 5 mg/kg DDP alone by UHI or by systemic administration. In the group given UHI of DDP (DDP-UHI) in combination with STS, there was a significantly better antitumour effect than seen in the group given DDP alone, as evaluated by the number of lung tumour nodules and survival time after inoculation of the transitional cell carcinoma into the lung. Nephrotoxicity, as assessed by increase in BUN levels, was completely avoided. Haematological toxicity effects assessed by decreases in WBC were slight but body-weight loss due to anorexia was severe.