Combination of vorinostat and low dose cytarabine for patients with azacitidine-refractory/relapsed high risk myelodysplastic syndromes

被引：15

作者：

Prebet, Thomas ^{[1
,2
]}

Braun, Thorsten ^{[3
]}

Beyne-Rauzy, Odile ^{[4
]}

Dreyfus, Francois ^{[5
]}

Stammatoullas, Aspasia ^{[6
]}

Wattel, Eric ^{[7
]}

Ame, Shanti

Raffoux, Emmanuel ^{[3
]}

Delaunay, Jacques

Charbonnier, Aude ^{[1
,2
]}

Ades, Lionel ^{[3
]}

Fenaux, Pierre ^{[3
]}

Vey, Norbert ^{[1
,2
]}

机构：

[1] Inst J Paoli I Calmettes, Dept Hematol, 232 Blvd St Margueritte, F-13009 Marseille, France

[2] Aix Marseille Univ, Marseille, France

[3] Hop Avicenne, AP HP, Dept Hematol, F-93009 Bobigny, France

[4] Hop Purpan, Dept Hematol, Toulouse, France

[5] Hop Cochin, AP HP, Dept Hematol, F-75674 Paris, France

[6] Ctr Henri Becquerel, Dept Hematol, F-76038 Rouen, France

[7] Hop Lyon Sud, Dept Hematol, Pierre Benite, France

来源：

LEUKEMIA RESEARCH | 2014年 / 38卷 / 01期

关键词：

Myelodysplasia; Epigenetic; Azacitidine failure; HDAC; SUBEROYLANILIDE HYDROXAMIC ACID; HISTONE DEACETYLASE INHIBITOR; CYTOSINE-ARABINOSIDE; ACUTE-LEUKEMIA; PHASE-I;

D O I：

10.1016/j.leukres.2013.07.023

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Outcome of patients with myelodysplastic syndrome after azacitidine failure is poor. In this population, we combined cytarabine (10-20mg/m(2)/day 14 days) with vorinostat (400mg/day) for escalating durations (7 days, 10 days and 14 days), and starting on day 1 (concomitant arm) or on day 14 (sequential arm) following a 3+3 phase I design. 40 patients were treated. Dose limiting toxicities were all seen in sequential arm. The overall response rate was 15% with 4 responses in concomitant arm (ORR=25%). We conclude that this combination is tolerable and concomitant administration might be less toxic and have better therapeutic effect (clinicaltrials.gov NCT00776503). (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：29 / 33

页数：5

共 23 条

[1]

Braun T, 2011, BLOOD

[2]

BUENETT AK, 2007, CANCER, V109, P1114

[3] Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer [J].

Cameron, EE ;

Bachman, KE ;

Myöhänen, S ;

Herman, JG ;

Baylin, SB .

NATURE GENETICS, 1999, 21 (01) :103-107

[4] Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia [J].

Cheson, Bruce D. ;

Greenberg, Peter L. ;

Bennett, John M. ;

Lowenberg, Bob ;

Wijermans, Pierre W. ;

Nimer, Stephen D. ;

Pinto, Antonio ;

Beran, Miloslav ;

de Witte, Theo M. ;

Stone, Richard M. ;

Mittelman, Moshe ;

Sanz, Guillermo F. ;

Gore, Steven D. ;

Schiffer, Charles A. ;

Kantarjian, Hagop .

BLOOD, 2006, 108 (02) :419-425

[5] PRESENT RESULTS OF THE TREATMENT OF MYELODYSPLASTIC SYNDROMES WITH LOW-DOSE CYTOSINE-ARABINOSIDE - PRELIMINARY-RESULTS OF A COOPERATIVE PROTOCOL (38 PATIENTS) AND REVIEW OF THE LITERATURE [J].

CHOMIENNE, C ;

NAJEAN, Y ;

DEGOS, L ;

THOMAS, G ;

BAUMELOU, E ;

CALVO, F ;

CASASSUS, P ;

CICCONE, F ;

FENAUX, P ;

GRIS, JC ;

GROSBOIS, B ;

GUERCI, O ;

LEPEU, G ;

RAIN, JD ;

ROLOVIC, A ;

TURPIN, F ;

SOUTEYRAND, F .

ACTA HAEMATOLOGICA, 1987, 78 :109-115

[6] Molecular origins of cancer: Epigenetics in cancer [J].

Esteller, Manel .

NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (11) :1148-1159

[7] A randomized study of 2 dose levels of intravenous clofarabine in the treatment of patients with higher-risk myelodysplastic syndrome [J].

Faderl, Stefan ;

Garcia-Manero, Guillermo ;

Jabbour, Elias ;

Ravandi, Farhad ;

Borthakur, Gautam ;

Estrov, Zeev ;

Gandhi, Varsha ;

Byrd, Anna L. ;

Kwari, Monica ;

Cortes, Jorge ;

Kantarjian, Hagop M. .

CANCER, 2012, 118 (03) :722-728

[8] Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study [J].

Fenaux, Pierre ;

Mufti, Ghulam J. ;

Hellstrom-Lindberg, Eva ;

Santini, Valeria ;

Finelli, Carlo ;

Giagounidis, Aristoteles ;

Schoch, Robert ;

Gattermann, Norbert ;

Sanz, Guillermo ;

List, Alan ;

Gore, Steven D. ;

Seymour, John F. ;

Bennett, John M. ;

Byrd, John ;

Backstrom, Jay ;

Zimmerman, Linda ;

McKenzie, David ;

Beach, C. L. ;

Silverman, Lewis R. .

LANCET ONCOLOGY, 2009, 10 (03) :223-232

[9] Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes [J].

Garcia-Manero, Guillermo ;

Yang, Hui ;

Bueso-Ramos, Carlos ;

Ferrajoli, Alessandra ;

Cortes, Jorge ;

Wierda, William G. ;

Faderl, Stefan ;

Koller, Charles ;

Morris, Gail ;

Rosner, Gary ;

Loboda, Andrey ;

Fantin, Valeria R. ;

Randolph, Sophia S. ;

Hardwick, James S. ;

Reilly, John F. ;

Chen, Cong ;

Ricker, Justin L. ;

Secrist, J. Paul ;

Richon, Victoria M. ;

Frankel, Stanley R. ;

Kantarjian, Hagop M. .

BLOOD, 2008, 111 (03) :1060-1066

[10] International scoring system for evaluating prognosis in myelodysplastic syndromes [J].

Greenberg, P ;

Cox, C ;

LeBeau, MM ;

Fenaux, P ;

Morel, P ;

Sanz, G ;

Sanz, M ;

Vallespi, T ;

Hamblin, T ;

Oscier, D ;

Ohyashiki, K ;

Toyama, K ;

Aul, C ;

Mufti, G ;

Bennett, J .

BLOOD, 1997, 89 (06) :2079-2088

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