A randomised comparison of the novel nucleoside analogue sapacitabine with low-dose cytarabine in older patients with acute myeloid leukaemia

被引：30

作者：

Burnett, A. K. ^{[1
]}

Russell, N. ^{[2
]}

Hills, R. K. ^{[1
]}

Panoskaltsis, N. ^{[3
]}

Khwaja, A. ^{[4
]}

Hemmaway, C. ^{[5
]}

Cahalin, P. ^{[6
]}

Clark, R. E. ^{[7
]}

Milligan, D. ^{[8
]}

机构：

[1] Cardiff Univ, Sch Med, Dept Haematol, Cardiff CF4 14XN, S Glam, Wales

[2] Nottingham Univ Hosp NHS Trust, Dept Haematol, Nottingham, England

[3] Northwick Pk Hosp & Clin Res Ctr, Harrow HA1 3UJ, Middx, England

[4] Univ Coll London Hosp, London, ON, Canada

[5] Queens Hosp, Romford, Essex, England

[6] Blackpool Victoria Hosp, Blackpool, England

[7] Royal Liverpool Univ Hosp, Dept Haematol, Liverpool, Merseyside, England

[8] Birmingham Heartlands Hosp, Dept Haematol, Birmingham B9 5ST, W Midlands, England

来源：

LEUKEMIA | 2015年 / 29卷 / 06期

关键词：

RISK MYELODYSPLASTIC SYNDROME; ACUTE NONLYMPHOCYTIC LEUKEMIA; CONVENTIONAL CARE REGIMENS; INTENSIVE CHEMOTHERAPY; ELDERLY-PATIENTS; ORAL SAPACITABINE; OPEN-LABEL; SURVIVAL; AML; REMISSION;

D O I：

10.1038/leu.2015.38

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The development of new treatments for older patients with acute myeloid leukaemia (AML) is an active area, but has met with limited success. Sapacitabine is a novel orally administered nucleoside analogue that has shown encouraging activity in unrandomised early-stage trials. We randomised 143 untreated patients with AML or with high-risk myelodysplastic syndrome (>10% marrow blasts) between sapacitibine and low-dose ara-C (LDAC) in our 'Pick a Winner' trial design. At the planned interim analysis there was no difference between LDAC and sapacitibine in terms of remission rate (CR/CRi, 27% vs 16% hazard ratio (HR) 1.98(0.90-4.39) P = 0.09), relapse-free survival (10% vs 14% at 2 years, HR 0.73(0.33-1.61) P = 0.4) or overall survival (OS; 12% vs 11% at 2 years, HR 1.24(0.86-1.78) P = 0.2). Sapacitibine was well tolerated, apart from more grade 3/4 diarrhoea. On the basis of these findings sapacitibine did not show sufficient evidence of benefit over LDAC for the trial to be continued.

引用

页码：1312 / 1319

页数：8

共 29 条

[1] Age and acute myeloid leukemia [J].

Appelbaum, FR ;

Gundacker, H ;

Head, DR ;

Slovak, ML ;

Willman, CL ;

Godwin, JE ;

Anderson, JE ;

Petersdorf, SH .

BLOOD, 2006, 107 (09) :3481-3485

[2] 2′-C-cyano-2′-deoxy-1-β-D-arabino-pentofuranosylcytosine:: A novel anticancer nucleoside analog that causes both DNA strand breaks and G2 arrest [J].

Azuma, A ;

Huang, P ;

Matsuda, A ;

Plunkett, W .

MOLECULAR PHARMACOLOGY, 2001, 59 (04) :725-731

[3] The addition of gemtuzumab ozogamicin to low-dose Ara-C improves remission rate but does not significantly prolong survival in older patients with acute myeloid leukaemia: results from the LRF AML14 and NCRI AML16 pick-a-winner comparison [J].

Burnett, A. K. ;

Hills, R. K. ;

Hunter, A. E. ;

Milligan, D. ;

Kell, W. J. ;

Wheatley, K. ;

Yin, J. ;

McMullin, M. F. ;

Dignum, H. ;

Bowen, D. ;

Russell, N. H. .

LEUKEMIA, 2013, 27 (01) :75-81

[4] The addition of arsenic trioxide to low-dose Ara-C in older patients with AML does not improve outcome [J].

Burnett, A. K. ;

Hills, R. K. ;

Hunter, A. ;

Milligan, D. ;

Kell, J. ;

Wheatley, K. ;

Yin, J. ;

McMullin, M-F ;

Cahalin, P. ;

Craig, J. ;

Bowen, D. ;

Russell, N. .

LEUKEMIA, 2011, 25 (07) :1122-1127

[5] A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment [J].

Burnett, Alan K. ;

Milligan, Donald ;

Prentice, Archie G. ;

Goldstone, Anthony H. ;

McMullin, Mary F. ;

Hills, Robert K. ;

Wheatley, Keith .

CANCER, 2007, 109 (06) :1114-1124

[6] Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival [J].

Burnett, Alan K. ;

Russell, Nigel H. ;

Hunter, Ann E. ;

Milligan, Donald ;

Knapper, Steven ;

Wheatley, Keith ;

Yin, John ;

McMullin, Mary F. ;

Ali, Sahra ;

Bowen, David ;

Hills, Robert K. .

BLOOD, 2013, 122 (08) :1384-1394

[7] The addition of the farnesyl transferase inhibitor, tipifarnib, to low dose cytarabine does not improve outcome for older patients with AML [J].

Burnett, Alan K. ;

Russell, Nigel H. ;

Culligan, Dominic ;

Cavanagh, Jamie ;

Kell, Jonathan ;

Wheatley, Keith ;

Virchis, Andra ;

Hills, Robert K. ;

Milligan, Donald .

BRITISH JOURNAL OF HAEMATOLOGY, 2012, 158 (04) :519-522

[8] European Development of Clofarabine as Treatment for Older Patients With Acute Myeloid Leukemia Considered Unsuitable for Intensive Chemotherapy [J].

Burnett, Alan K. ;

Russell, Nigel H. ;

Kell, Jonathan ;

Dennis, Michael ;

Milligan, Donald ;

Paolini, Stefania ;

Yin, John ;

Culligan, Dominic ;

Johnston, Peter ;

Murphy, John ;

McMullin, Mary-Frances ;

Hunter, Ann ;

Das-Gupta, Emma ;

Clark, Richard ;

Carr, Robert ;

Hills, Robert K. .

JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (14) :2389-2395

[9] The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial [J].

Burnett, Alan K. ;

Milligan, Donald ;

Goldstone, Anthony ;

Prentice, Archibald ;

McMullin, Mary-Frances ;

Dennis, Michael ;

Sellwood, Elizabeth ;

Pallis, Monica ;

Russell, Nigel ;

Hills, Robert K. ;

Wheatley, Keith .

BRITISH JOURNAL OF HAEMATOLOGY, 2009, 145 (03) :318-332

[10] A CRITICAL-APPRAISAL OF LOW-DOSE CYTOSINE-ARABINOSIDE IN PATIENTS WITH ACUTE NONLYMPHOCYTIC LEUKEMIA AND MYELODYSPLASTIC SYNDROMES [J].

CHESON, BD ;

JASPERSE, DM ;

SIMON, R ;

FRIEDMAN, MA .

JOURNAL OF CLINICAL ONCOLOGY, 1986, 4 (12) :1857-1864

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