title: Vosaroxin and vosaroxin plus low-dose Ara-C (LDAC) vs low-dose Ara-C alone in older patients with acute myeloid leukemia.
abstract: The development of new treatments for older patients with acute myeloid leukemia is an active area, but has met with limited success. Vosaroxin, a quinolone-derived intercalating agent has several properties that could prove beneficial. Initial clinical studies showed it to be well-tolerated in older patients with relapsed/refractory disease. In vitro data suggested synergy with cytarabine (Ara-C). To evaluate vosaroxin, we performed 2 randomized comparisons within the "Pick a Winner" program. A total of 104 patients were randomized to vosaroxin vs low-dose Ara-C (LDAC) and 104 to vosaroxin + LDAC vs LDAC. When comparing vosaroxin with LDAC, neither response rate (complete recovery [CR]/complete recovery with incomplete count recovery [CRi], 26% vs 30%; odds ratio [OR], 1.16 (0.49-2.72); P = .7) nor 12-month survival (12% vs 31%; hazard ratio [HR], 1.94 [1.26-3.00]; P = .003) showed benefit for vosaroxin. Likewise, in the vosaroxin + LDAC vs LDAC comparison, neither response rate (CR/CRi, 38% vs 34%; OR, 0.83 [0.37-1.84]; P = .6) nor survival (33% vs 37%; HR, 1.30 [0.81-2.07]; P = .3) was improved. A major reason for this lack of benefit was excess early mortality in the vosaroxin + LDAC arm, most obviously in the second month following randomization. At its first interim analysis, the Data Monitoring and Ethics Committee recommended closure of the vosaroxin-containing trial arms because a clinically relevant benefit was unlikely.
authors: Department of Haematology, Christie Hospital, Manchester, United Kingdom;
authors: Mike
authors: M
authors: Dennis
authors: Department of Haematology, Nottingham University Hospital National Health Service Trust, Nottingham, United Kingdom;
authors: Nigel
authors: N
authors: Russell
authors: Department of Haematology, Cardiff University School of Medicine, Cardiff, United Kingdom;
authors: Robert K
authors: RK
authors: Hills
authors: Department of Haematology, Queen's Hospital, Romford, United Kingdom;
authors: Claire
authors: C
authors: Hemmaway
authors: Department of Haematology, Imperial College, Northwick Park Hospital Campus, London, United Kingdom;
authors: Nicki
authors: N
authors: Panoskaltsis
authors: Department of Haematology, Belfast City Hospital, Belfast, United Kingdom;
authors: Mary-Frances
authors: MF
authors: McMullin
authors: Department of Haematology, Rigshospitalet, Copenhagen, Denmark;
authors: Lars
authors: L
authors: Kjeldsen
authors: Department of Haematology, Queen Alexandra Hospital, Portsmouth, United Kingdom;
authors: Helen
authors: H
authors: Dignum
authors: Department of Haematology, Cardiff University School of Medicine, Cardiff, United Kingdom;
authors: Ian F
authors: IF
authors: Thomas
authors: Department of Haematology, Royal Liverpool University Hospital, Liverpool, United Kingdom; and.
authors: Richard E
authors: RE
authors: Clark
authors: Department of Haematology, Heartlands Hospital, Birmingham, United Kingdom.
authors: Don
authors: D
authors: Milligan
authors: Department of Haematology, Cardiff University School of Medicine, Cardiff, United Kingdom;
authors: Alan K
authors: AK
authors: Burnett
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009287:Naphthyridines / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D015996:Survival Rate; D013844:Thiazoles / Q000008:administration & dosage
chemical_list: D009287:Naphthyridines; D013844:Thiazoles; D003561:Cytarabine; C485113:vosaroxin