Efficacy of Two‐route Chemotherapy Using Intraperitoneal Neocarzinostatin and Its Antidote, Intravenous Tiopronin, for Peritoneally Disseminated Tumors in Mice

Abstract

We assessed the efficacy of “two‐route chemotherapy (TRC)” using neocarzinostatin (NCS) given ip and its antidote, N‐(2‐mercaptopropionyl)‐glycine (tiopronin), given iv for peritoneally disseminated tumors in mice. Whether or not the single iv administration of tiopronin (800 mg/kg) at various times after NCS ip would decrease the lethal toxicity induced by NCS ip was given attention. When compared with the LD ₅₀ (4.4 mg/kg) of NCS ip alone, simultaneous or postadministration of tiopronin together with NCS ip increased the LD ₅₀ of NCS ip by 2.8 to 7.6 fold in a time‐dependent manner. Chemotherapy experiments on ip disseminated tumors in mice were done to compare the antitumor effects of the following treatments, at two dose levels (75 and 100% of LD ₁₀) of NCS, with or without tiopronin: treatment with NCS ip alone and combined chemotherapy using NCS ip plus tiopronin iv, simultaneously or postadministered. Based on the survival time of the treated mice, the groups given NCS plus tiopronin (postadministration, 15 or 25 min later) showed a significantly superior survival time to that of the group given NCS ip alone. The side effects, evaluated in terms of the changes in body weight and number of WBC of the mice, were not significantly different among the groups treated with 100% of LD ₁₀ of NCS.