Experimental antitumor activity of the amsacrine analogue CI-921

CI-921 is a di-substituted analogue of amsacrine currently in phase 1 clinical trial. CI-921 was developed to clinical trial largely on the basis of a series of studies at five cancer research laboratories that demonstrated its improved spectrum and degree of activity relative to those of amsacrine against murine tumor models. The tumor models studied included lung, colon, and mammary carcinomas and encompassed a wide range of biologic properties and chemosensitivities. CI-921 had significant activity against 16 of 19 (84%) tumor models examined. The activity of CI-921 was superior to that of amsacrine in 10 of 14 tumor systems that were sensitive to at least one of the agents and for which comparable data existed. In the remaining four systems, CI-921 and amsacrine were equivalent in activity. CI-921 was found to be roughly equipotent with amsacrine on a milligram-per-kilogram (body wt) basis and was found to have significantly higher activity when given orally.