Enhancement of the effectiveness of daunorubicin (NSC-82151) or adriamycin (NSC-123127) against early mouse L1210 leukemia with ICRF-159 (NSC-129943)

Abstract

The LD50 of intraperitoneally (ip) injected daunorubicin in nonleukemic mice (1.8 mg/kg, q4d times 3) can be increased several fold by the concomitant ip injection of ICRF-159. In addition, the survival of leukemic mice treated with daunorubicin and ICRF-159 on Days 1, 5, and 9 after ip inoculation of L1210 tumor cells was substantially greater than after treatment with either drug alone. This potentiation of survival with combination treatment usually occurred with doses of daunorubicin greater than the LD50 of daunorubicin alone. The LD50 of subcutaneously (sc) injected daunorubicin alone (14.0 mg/kg, q4d times 3) was not increased by concomitant ip treatment with ICRF-159. However, when leukemic mice were treated sc with daunorubicin and ip with ICRF-159 on Days 1, 5, and 9 after ip injection of L1210 leukemia cells, survival was greater than with treatment with either drug alone. The toxicity of ip injected adriamycin was not reduced by ICRF-159, but treatment of leukemic mice with this combination was more effective in prolonging survival than treatment with either drug alone. Combination treatment with daunorubicin plus ICRF-159 showed much less therapeutic enhancement against sc implanted L1210 leukemia than against the ip implanted tumor.