Mike Dennis
Vosaroxin and vosaroxin plus low-dose Ara-C (LDAC) vs low-dose Ara-C alone in older patients with acute myeloid leukemia
Dennis, Mike; Russell, Nigel; Hills, Robert K.; Hemmaway, Claire; Panoskaltsis, Nicki; McMullin, Mary-Frances; Kjeldsen, Lars; Dignum, Helen; Thomas, Ian F.; Clark, Richard E.; Milligan, Don; Burnett, Alan K.
Authors
Nigel Russell
Robert K. Hills
Claire Hemmaway
Nicki Panoskaltsis
Mary-Frances McMullin
Lars Kjeldsen
Helen Dignum
Ian F. Thomas
Richard E. Clark
Don Milligan
Alan K. Burnett
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.
Journal Article Type | Article |
---|---|
Acceptance Date | Mar 6, 2015 |
Online Publication Date | May 7, 2015 |
Publication Date | May 7, 2015 |
Deposit Date | Jul 12, 2017 |
Journal | Blood |
Print ISSN | 0006-4971 |
Electronic ISSN | 1528-0020 |
Publisher | American Society of Hematology |
Peer Reviewed | Peer Reviewed |
Volume | 125 |
Issue | 19 |
Pages | 2923-2932 |
DOI | https://doi.org/10.1182/blood-2014-10-608117 |
Public URL | https://nottingham-repository.worktribe.com/output/1112718 |
Publisher URL | https://ashpublications.org/blood/article/125/19/2923/34272/Vosaroxin-and-vosaroxin-plus-low-dose-Ara-C-LDAC |
PMID | 25805811 |
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