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.
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced; D000880:Anthraquinones / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects; D016026:Bone Marrow Transplantation; D002986:Clinical Trials as Topic; D003561:Cytarabine / Q000627:therapeutic use; D005260:Female; D006321:Heart / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D007951:Leukemia, Myeloid / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone; D009325:Nausea / Q000139:chemically induced; D013318:Stroke Volume / Q000187:drug effects; D014839:Vomiting / Q000139:chemically induced
D000880:Anthraquinones; D000970:Antineoplastic Agents; D003561:Cytarabine; D008942:Mitoxantrone