2-ROUTE CHEMOTHERAPY USING HIGH-DOSE IP CISPLATIN AND IV SODIUM THIOSULFATE, ITS ANTIDOTE, FOR PERITONEALLY DISSEMINATED CANCER IN MICE

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 68  (11) , 1367-1373
Abstract
The effects of 2-route chemotherapy (TRC) using cisplatin given i.p. and its antidote, sodium thiosulfate (STS), given i.v. were studied in mice bearing peritoneally disseminated cancer. Initially, a pharmacokinetic analysis of cisplatin given i.p. and STS given i.v. or s.c. was made. The plasma concentrations of non-protein-bound and total Pt increased rapidly to a maximum at 10 min after i.p. administration of cisplatin alone. When STS alone was given s.c., the peak level in the plasma was much lower than that given i.v. The superiority of the i.v. route for STS administration was observed in the lethal toxicity tests. The i.v. administration of STS to mice 1 min after cisplatin given i.p. was the best protocol to protect against the lethal toxicity of cisplatin. The protective conditions were applied to TRC in which STS was given i.v. 1 min after i.p. cisplatin to mice bearing peritoneally disseminated cancer. Significantly superior antitumor effects were observed in mice given TRC by evaluating survival time as compared with mice given a single treatment with cisplatin at an equitoxic level. The nephrotoxic and hematotoxic effects were slight in TRC.