"Two-route chemotherapy" using high-dose ip cisplatin and iv sodium thiosulfate, its antidote, for peritoneally disseminated cancer in mice.

We studied the effects of "two-route chemotherapy (TRC)" using cisplatin given ip and its antidote, sodium thiosulfate (STS), given iv on mice bearing peritoneally disseminated cancer. Initially, a pharmacokinetic analysis of cisplatin given ip and STS given iv or sc was made. The plasma concentrations of non-protein-bound and total platinum increased rapidly to a maximum at 10 mins after ip administration of cisplatin alone. When STS alone was given sc, the peak level in the plasma was much lower than that given iv. The superiority of the iv route for STS administration was observed in the lethal toxicity tests. The iv administration of STS to mice 1 min after cisplatin given ip was the best protocol to protect against the lethal toxicity of cisplatin. The protective conditions were applied to TRC in which STS was given iv 1 min after ip 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.