DMP 840, a novel bis-
naphthalimide, was evaluated for antitumor efficacy in several
tumor models in mice. As measured by a
tumor growth inhibition assay, i.v. administration of
DMP 840 to athymic nude mice at doses at or below the maximum tolerated dose resulted in curative activity against four human solid
tumor xenografts, MX-1 mammary
carcinoma, CX-1 and DLD-2
colon adenocarcinomas, and LX-1 lung
carcinoma, producing full or incomplete regressions and/or percent
tumor growth inhibition of > or = 96%. The efficacy of
DMP 840 in the models was dose dependent. The activity of
DMP 840 against the human
tumors surpassed that demonstrated by several clinically used and investigational
anticancer agents. In long-term growth delay studies,
DMP 840 induced full regressions in 20 of 20 mice bearing MX-1
tumors, and
tumors in one-half of these mice remained regressed for over 5 months. In addition,
DMP 840 was curative against exponentially growing DLD-2
tumors staged at 500 mg and MX-1
tumors staged at 1000 mg. The bis-
naphthalimide was equally efficacious when administered i.v. or i.p. but was slightly less active after oral dosing. Against both the MX-1 mammary
carcinoma and the DLD-2
colon adenocarcinoma, some measure of schedule dependence was observed; the optimum schedule was daily for 9 days. Against L1210 and P388 murine
leukemias,
DMP 840 demonstrated little or no activity and was inactive against B16 murine
melanoma. Overall, these results suggest that
DMP 840 may be a human solid
tumor selective
cytotoxic agent.