MKT-077, LOCALIZED LIPOPHILIC CATION - ANTITUMOR-ACTIVITY AGAINST HUMAN TUMOR XENOGRAFTS SERIALLY TRANSPLANTED INTO NUDE-MICE

Background: In in vitro experiments, the localized lipophilic cation, MKT-077, demonstrated time- and concentration-dependent antitumor acti vity. In the present experiment, the in vivo antitumor activity of MKT -077 was evaluated using human tumor xenografts serially transplanted into nude mice. Materials and Methods: The antitumor efficacy of MKT-0 77 against five xenografts inoculated subcutaneously into nude mice wa s studied. Treatment with MKT-077 was initiated when the tumors starte d exponential growth. The antitumor activity of MKT-077 was assessed b y a) the lowest value of the relative mean tumor weight of the treated :control tumors (T/CRW), where relative weight (RW) represented the ch ange fr om baseline weight; and by b) the unadjusted weight of treated tumors at the end of the experiment. Results: When MKT-077 was admini stered continuously using the Osmotic Micropump(TM), antitumor activit y was positively correlated with exposure time and drug concentration from 7.5 to 40 mg/kg/day. The maximum tolerated dose was 20 mg/kg/day for 7 days. Co-4 (human colon cancer), St-4 (human gastric cancer), an d CRL1420 (human pancreatic cancer) were evaluated as sensitive to MKT -077 in tested 5 strains. Conclusion: The antitumor activity of MKT-07 7 was confirmed using human tumor xenografts in nude mice.