HO-221, a derivative of benzoylphenylurea, is a newly developed anticancer
drug which was found to show an excellent antitumor effect against transplantable murine
tumors by the novel mechanism of action. This study was designed to evaluate the antitumor effect of
HO-221 and to establish the optimum regimen, using seven human gastrointestinal and breast
cancers xenografted in nude mice. Better antitumor effect of
HO-221 by
oral administration was observed when it was suspended in larger volume of the vehicle. Moreover, the effect increased by the multiple intermittent administration compared to the single treatment. Best antitumor effect was observed by
oral administration of 75 mg/kg (0.1 ml/10 g mouse
body weight) repeated twice weekly for a total of eight times or 300 mg/kg (0.2 ml/10 g mouse
body weight) repeated once weekly for a total of four times. The antitumor effects of these two regimens were approximately equal except against H-31, the former regimen being more effective. When the
tumor growth inhibition rate (IR) over 58% was rated as "effective", the above two regimens were equally effective against 4 of 7
cancers, H-111, H-154, H-143 and H-31. While
HO-221 was not effective to a
gastric cancer line, H-81, which was most susceptible to the variety of existing
anticancer agents, but effective to another
gastric cancer line, H-111, which was relatively resistant to conventional cytocidal agents. From the aspect of chemosensitivity spectrum, this
drug revealed a rather different pattern compared to other
antimetabolites. Although
oral administration volume is limited in small animal model, enhancing its antitumor effect may be possible in clinical application by contriving the method of administration.
HO-221 is, thus, considered to be a promising
drug for further study.