SYNERGISTIC ANTITUMOR-ACTIVITY OF COMBINATION CHEMOTHERAPY WITH MITOMYCIN-C AND CISPLATIN AGAINST HUMAN GASTRIC-CANCER XENOGRAFTS IN NUDE-MICE

A new combined cancer chemotherapy regimen of mitomycin C (MMC) and ci splatin (DDP) showed synergistic antitumor activity against human gast ric cancer xenografts St-40 and SC-1-NU in BALB/c nu/nu mice. The drug s were administered intraperitoneally at doses of 2 or 4 mg/kg for MMC and 3 or 6 mg/kg for DDP, respectively. To clarify the schedule-depen dent antitumor activity of MMC and DDP against St-40 and SC-1-NU, diff erent sequential therapies were conducted. Simultaneous administration of these agents showed the highest antitumor activity against SC1-NU among the three regimens used, whereas the sequence of MMC followed by DDP showed higher antitumor activity than the reverse sequence agains t St-40. The intratumoral concentration of platinum was significantly increased in St-40 treated with the sequence MMC to DDP, in comparison with the sequence DDP to MMC. The maximum tolerated dose (MTD) of thi s combination was 4 mg MMC plus 6 mg DDP per kg in all the combination s, and these MTDs were 2/3 of the corresponding values for their singl e use. Since this combination increased the antitumor activity of each single agent without any increase in their toxicity, it would appear to be useful clinically. (C) 1994 Wiley-Liss, Inc.