{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:22:09Z","timestamp":1790680929197,"version":"4.1.0"},"reference-count":47,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"3","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2020,1,20]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> DNA-hypomethylating agents are studied in combination with other epigenetic drugs, such as histone deacetylase inhibitors or differentiation inducers (eg, retinoids), in myeloid neoplasias. A randomized, phase II trial with a 2 \u00d7 2 factorial design was conducted to investigate the effects of the histone deacetylase inhibitor valproate and all- trans retinoic acid (ATRA) in treatment-naive elderly patients with acute myeloid leukemia (AML). <\/jats:p><\/jats:sec><jats:sec><jats:title>PATIENTS AND METHODS<\/jats:title><jats:p> Two hundred patients (median age, 76 years; range, 61-92 years) ineligible for induction chemotherapy received decitabine (20 mg\/m<jats:sup>2<\/jats:sup> intravenously, days 1 to 5) alone (n = 47) or in combination with valproate (n = 57), ATRA (n = 46), or valproate + ATRA (n = 50). The primary endpoint was objective response, defined as complete and partial remission, tested at a one-sided significance level of \u03b1 = .10. Key secondary endpoints were overall survival, event-free survival, and progression-free survival and safety. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> The addition of ATRA resulted in a higher remission rate (21.9% with ATRA v 13.5% without ATRA; odds ratio, 1.80; 95% CI, 0.86 to 3.79; one-sided P = .06). For valproate, no effect was observed (17.8% with valproate v 17.2% without valproate; odds ratio, 1.06; 95% CI, 0.51 to 2.21; one-sided P = .44). Median overall survival was 8.2 months with ATRA v 5.1 months without ATRA (hazard ratio, 0.65; 95% CI, 0.48 to 0.89; two-sided P = .006). Improved survival was observed across risk groups, including patients with adverse cytogenetics, and was associated with longer response duration. With valproate, no survival difference was observed. Toxicities were predominantly hematologic, without relevant differences between the 4 arms. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> The addition of ATRA to decitabine resulted in a higher remission rate and a clinically meaningful survival extension in these patients with difficult-to-treat disease, without added toxicity. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.19.01053","type":"journal-article","created":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T20:59:19Z","timestamp":1575406759000},"page":"257-270","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":90,"title":["Valproate and Retinoic Acid in Combination With Decitabine in Elderly Nonfit Patients With Acute Myeloid Leukemia: Results of a Multicenter, Randomized, 2 \u00d7 2, Phase II Trial"],"prefix":"10.1200","volume":"38","author":[{"given":"Michael","family":"L\u00fcbbert","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany"},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Grishina","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Schmoor","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard F.","family":"Schlenk","sequence":"additional","affiliation":[{"name":"University Hospital of Ulm, Ulm, Germany"},{"name":"Heidelberg University Hospital, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Jost","sequence":"additional","affiliation":[{"name":"University Hospital Rheinisch-Westf\u00e4lische Technische Hochschule Aachen University, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Crysandt","sequence":"additional","affiliation":[{"name":"University Hospital Rheinisch-Westf\u00e4lische Technische Hochschule Aachen University, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Heuser","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicitas","family":"Thol","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut R.","family":"Salih","sequence":"additional","affiliation":[{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus M.","family":"Schittenhelm","sequence":"additional","affiliation":[{"name":"Eberhard-Karls-University, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Germing","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Heinrich-Heine University, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Kuendgen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Heinrich-Heine University, D\u00fcsseldorf, Germany"},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina S.","family":"G\u00f6tze","sequence":"additional","affiliation":[{"name":"Technical University of Munich, Munich, Germany"},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Walter","family":"Lindemann","sequence":"additional","affiliation":[{"name":"Catholic Hospital, Hagen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"M\u00fcller-Tidow","sequence":"additional","affiliation":[{"name":"Heidelberg University Hospital, Heidelberg, Germany"},{"name":"University Hospital of M\u00fcnster, M\u00fcnster, Germany"},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Heil","sequence":"additional","affiliation":[{"name":"Klinikum L\u00fcdenscheid, L\u00fcdenscheid, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Scholl","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Jena, Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gesine","family":"Bug","sequence":"additional","affiliation":[{"name":"University Hospital Frankfurt, Goethe University, Frankfurt, Germany"},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Schwaenen","sequence":"additional","affiliation":[{"name":"Hospital Esslingen, Esslingen, Germany"},{"name":"Offenburg Hospital, Offenburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aristoteles","family":"Giagounidis","sequence":"additional","affiliation":[{"name":"Marien-Hospital D\u00fcsseldorf, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Neubauer","sequence":"additional","affiliation":[{"name":"University Clinic Gie\u00dfen\/Marburg, Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Krauter","sequence":"additional","affiliation":[{"name":"St\u00e4dtisches Klinikum Braunschweig, Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfram","family":"Brugger","sequence":"additional","affiliation":[{"name":"Hospital Villingen-Schwenningen, Villingen-Schwenningen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maike","family":"De Wit","sequence":"additional","affiliation":[{"name":"Vivantes Klinikum Neukoelln, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"W\u00e4sch","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Becker","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany"},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette M.","family":"May","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justus","family":"Duyster","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany"},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstanze","family":"D\u00f6hner","sequence":"additional","affiliation":[{"name":"University Hospital of Ulm, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold","family":"Ganser","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Hackanson","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany"},{"name":"Universit\u00e4tsklinikum Augsburg, Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"D\u00f6hner","sequence":"additional","affiliation":[{"name":"University Hospital of Ulm, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the DECIDER Study Team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1406184"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.07.056"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.07.011"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3889"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.38.9429"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-01-621664"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.048231"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-015-2547-0"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1605949"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0257-z"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/5047"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2016.1228927"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1300874"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(90)90086-D"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075258"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-03-078576"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.106"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-03-009142"},{"key":"B19","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1186\/s12885-015-1432-5","volume":"15","author":"Grishina O","year":"2015","journal-title":"BMC Cancer"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-235358"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23375"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-375758"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30010-X"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-08-868752"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.168732"},{"key":"B26","volume-title":"EHA 23rd Congress","author":"DiNardo CD","year":"2018"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2015.02.033"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.244"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2014.115055"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/624627"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22496"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-016-2810-z"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.13378"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-016-2681-3"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21589"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2726"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21552"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07449.x"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-017-3620-y"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.29085"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.38.5732"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.01.149"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-016-1878-5"},{"key":"B44","first-page":"1513","volume":"91","author":"Deschler B","year":"2006","journal-title":"Haematologica"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.8616"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1200\/EDBK_239097"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.192468"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.19.01053","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T07:15:39Z","timestamp":1653808539000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.19.01053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,20]]},"references-count":47,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,1,20]]}},"alternative-id":["10.1200\/JCO.19.01053"],"URL":"https:\/\/doi.org\/10.1200\/jco.19.01053","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,20]]},"assertion":[{"value":"2019-10-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}