Vosaroxin and vosaroxin plus low-dose Ara-C (LDAC) vs low-dose Ara-C alone in older patients with acute myeloid leukemia


Autoria(s): 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
Data(s)

07/05/2015

Resumo

<p>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.</p>

Identificador

http://pure.qub.ac.uk/portal/en/publications/vosaroxin-and-vosaroxin-plus-lowdose-arac-ldac-vs-lowdose-arac-alone-in-older-patients-with-acute-myeloid-leukemia(63cb9284-e5d3-478f-bf3a-b428e40fc36b).html

http://dx.doi.org/10.1182/blood-2014-10-608117

Idioma(s)

eng

Direitos

info:eu-repo/semantics/restrictedAccess

Fonte

Dennis , M , Russell , N , Hills , R K , Hemmaway , C , Panoskaltsis , N , McMullin , M-F , Kjeldsen , L , Dignum , H , Thomas , I F , Clark , R E , Milligan , D & Burnett , A K 2015 , ' Vosaroxin and vosaroxin plus low-dose Ara-C (LDAC) vs low-dose Ara-C alone in older patients with acute myeloid leukemia ' Blood , vol 125 , no. 19 , pp. 2923-32 . DOI: 10.1182/blood-2014-10-608117

Tipo

article