The role of mitozantrone in the treatment of acute leukaemia.

Mitozantrone (MTZ; Novantrone), 1,4-dihydroxy-5,8-bis-[(2-[(2-hydroxyethyl)amino]ethyl]amino)-9,10- anthracenedione dihydrochloride (NSC 302739), is a synthetic anthracenedione with intercalating properties. Activity has been shown in preclinical studies in mice bearing intraperitoneal P388 and L1210 leukaemias and a variety of solid tumours. Three sequential studies to examine the activity, toxicity and scheduling of MTZ in acute leukaemia or chronic granulocytic leukaemia in myeloid transformation were undertaken in relapsed and/or refractory disease in patients up to the age of 70. Single-dose treatment up to 32 mg/m2 showed little activity but in a 5-day schedule (10 mg/m2/day) MTZ gave a 24% complete remission rate in relapsed and/or resistant acute leukaemia. In a phase III study in which MTZ was given in a similar schedule combined with a 7-day infusion of cytosine arabinoside (Ara-C; 100 mg/m2/day), 68% of patients were rendered leukaemia-free. In studies from other centres, similar very encouraging results have been obtained where MTZ has been combined with high-dose Ara-C or VP16/213.