Antileukemic Activity of 4-Demethoxydaunorubicin in Mice

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Abstract
4-demethoxydaunorubicin was tested against experimental mouse leukemias, in comparison with doxorubicin and daunorubicin. 4-demethoxydaunorubicin, administered ip to mice bearing ascitic L1210 or F388 leukemia was 5 times more potent than daunorubicin and 10 times more potent than doxorubicin (potency established in relation to optimal antitumor doses). At the optimal doses, 4-demethoxydaunorubicin was as active as daunorubicin and less active than doxorubicin. 4-demethoxydaunorubicin, administered iv was 8 times more potent than daunorubicin and 4–5 times more potent than doxorubicin. At the optimal doses, 4-demethoxydaunorubicin was markedly more active than daunorubicin or doxorubicin in mice injected iv with 105 L1210 leukemia cells (early or late leukemia) or with 102 Gross leukemia cells. In mice given 2 × 106 Gross leukemia cells iv, 4-demethoxydaunorubicin was as active as doxorubicin when treatment was given iv on day 1, or on days 1 to 3 or 1 to 5. The optimal intermittent schedule was treatment on days 1, 5 and 9 for 4-demethoxydaunorubicin, and on days 1, 3 and 6 for daunorubicin and doxorubicin. 4-demethoxydaunorubicin administered orally was highly active against ascitic P388 leukemia and against L1210 and Gross leukemia inoculated iv.