[Two-route chemotherapy using a combination of anticancer agents and antidotes]

We studied the effect of "two-route chemotherapy (TRC)" in which an anticancer drug and its antidote are respectively administered locally and systemically. This therapy reduced the side effects and consequently enabled an increased dose of anticancer agents to be given. The first trial of TRC using a combination of nitrogen mustard N-oxide and its antidote cysteine was effective for the treatment of metastatic liver tumors in rats. Recently, we obtained a remarkable antitumor effect by giving a combination of cis-diamminedichloroplatinum (II) (CDDP) and sodium thiosulfate (STS) for peritoneal dissemination, bladder tumors, and liver and lung metastasis, in experimental animals, based on the evidence that STS inactivates the toxicity of DDP. This TRC using DDP and STS is now under clinical trial, and remarkable antitumor effects without nephrotoxicity have been observed. We also present evidence that the protective effect of STS against DDP toxicity is mainly due to the inactivation of active platinum in the blood stream and partly due to the diuretic effect of STS.