Antitumor activities of a novel 9-aminoanthracycline (SM-5887) against mouse experimental tumors and human tumor xenografts

Abstract

The antitumor effects of SM-5887, a totally synthetic 9-aminoanthracycline derivative, were evaluated in six murine experimental tumor systems (P388, Ehrlich carcinoma, sarcoma 180, Lewis lung carcinoma, B16 melanoma and colon 38) and nine human tumor-nude mouse systems (one breast cancer, two lung cancers and six gastric cancers). Characteristically SM-5887 showed excellent antitumor activities, superior to adriamycin (ADR), against human tumor xenografts, although its activities against murine experimental tumors were almost equal to those of ADR. When the human tumors were implanted sc in female athymic mice (BALB/c, nu/nu) and their volume reached 100-300 mm3, SM-5887 and ADR were injected iv. All nine human tumors tested showed statistically significant responses to SM-5887, and 7 of them were strongly suppressed in their growth by SM-5887 so that minimum T/C values were less than 30% at the maximum tolerated dose (MTD, 25 mg/kg) with a single iv injection. Compared with ADR, SM-5887 was statistically more effective in five tumors (one breast, one lung and three gastric), equal in two tumors (two gastric), and less potent in two tumors (one lung and one gastric). In addition, the 10-day-interval repeated iv treatments with SM-5887 at the MTD (25 mg/kg) resulted in remarkably potent antitumor effects (including complete regression) against human gastric cancer, 4-1ST, implanted in nude mice without enhancement of toxic effects. SM-5887 was also effective against ip-inoculated P388 by oral administration as well as iv injection.