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.