[Two-route chemotherapy using the anticancer drug cis-diamminedichloroplatinum(II) and its antidote, sodium...

We described the efficacy of "two-route chemotherapy (TRC)", in which the anticancer drug, cis-diamminedichloroplatinum (II) (DDP), is injected locally, in combination with its antidote, sodium thiosulfate (STS), given systemically. First, we tested the protective effect of sulfur-containing compounds against DDP toxicity, and found STS to be the most potent antidote of DDP. On the basis of this finding, we developed TRC using DDP and STS, and applied it for liver and lung metastasis, bladder cancer, and peritoneal disseminated tumors in experimental animals, resulting in remarkable antitumor effects without serious side effects, especially nephrotoxicity. Furthermore, we obtained an optimal increase in the lifespan of rats bearing limb tumors when we tried TRC in combination with the angiotensin II (AT-II)-induced hypertension method. We also clarified that the protection of STS against DDP toxicity was mainly due to the diminution of the active platinum level in blood. We briefly reviewed the clinical trials of TRC, and discussed the improvements which still have to be made.