Mitozantrone (HCl)

Mitozantrone (HCl) is a parenteral, synthetic antineoplastic agent. Chemically, Mitozantrone (HCl) is anthracenedione and is structurally similar to the anthracyclines, doxorubicin, daunorubicin and idarubicin. Mitozantrone (HCl) is sometimes substituted for doxorubicin or daunorubicin because it has considerably less cardiotoxicity and mitoxantrone is not a vesicant as are the other anthracyclines. Mitozantrone (HCl) is used in combination with other chemotherapeutic agents for acute nonlymphocytic leukemias, specifically, for myelogenous, promyelocytic, monocytic and erythroid acute leukemias. Mitozantrone (HCl) is also being studied in the treatment of breast carcinomas and refractory non-Hodgkin's lymphomas. This drug was approved by the FDA in 1987. Althoughthe exact mechanism of action is unknown, it appears to bind to DNA by intercalation between base pairs and by a nonintercalative electrostatic interaction, which inhibits DNA and RNA synthesis. It also inhibits topoisomerase II, an enzyme known to be important for the repair of damaged DNA. The interaction with topoisomerase II leads to double strand DNA breaks. The drug is not cell phase specific, but appears to be most active in the late G-2 phase. It has a cytocidal effect on both nonproliferating and proliferating cultured human cells.