Sequential studies on the role of mitoxantrone in the treatment of acute leukemia.

Mitoxantrone (Novantrone; 1, 4-dihydroxy-5, 8-bis [[2-[(2-hydroxyethyl) amino]ethyl]amino-] 9, 10 anthracenedione dihydrochloride (NSC 301739] is a synthetic anthracenedione with intercalating properties. Activity has been shown in preclinical studies in mice bearing intraperitoneal P388 and L1210 leukaemias, ADJ-Pc6 plasmacytoma and a variety of solid tumours. In a phase I/II collaborative study fourteen consecutive patients with relapsed or primarily refractory acute leukaemia received a single infusion of mitoxantrone (20-32 mg/m2) at fourteen-day intervals. Antileukaemic activity was seen but there were no complete remissions and toxicity was minimal. Mitoxantrone was subsequently given in a five-day schedule at a dose of 10mg/m2 daily to twenty-one patients with relapsed or refractory acute leukaemia or chronic myeloid leukaemia in blast crisis (CML-BC). Four of five patients in first relapse of acute non-lymphoblastic leukaemia (ANLL) achieved a complete remission (CR). The overall response rate (CR + partial remission (PR] was 48%. In an ongoing phase III study the same (5-day) mitoxantrone treatment has been given in conjunction with a 7-day continuous infusion of cytosine arabinoside (Ara-C) in a kinetically designed schedule based upon the preclinical studies of the Mount Sinai group.