{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T09:22:17Z","timestamp":1774430537642,"version":"3.50.1"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,11,17]],"date-time":"2014-11-17T00:00:00Z","timestamp":1416182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015234","name":"Sunesis","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015234","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>This phase 2 study (<jats:italic>N\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>116) evaluated single\u2010agent vosaroxin, a first\u2010in\u2010class anticancer quinolone derivative, in patients \u226560\u00a0years of age with previously untreated unfavourable prognosis acute myeloid leukaemia. Dose regimen optimization was explored in sequential cohorts (<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>: 72\u00a0mg\/m<jats:sup>2<\/jats:sup>\u00a0d 1, 8, 15; <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>: 72\u00a0mg\/m<jats:sup>2<\/jats:sup>\u00a0d 1, 8; <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>: 72\u00a0mg\/m<jats:sup>2<\/jats:sup> or 90\u00a0mg\/m<jats:sup>2<\/jats:sup>\u00a0d 1, 4). The primary endpoint was combined complete remission rate (complete remission [<jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>] plus <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content> with incomplete platelet recovery [<jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>p]). Common (&gt;20%) grade \u22653 adverse events were thrombocytopenia, febrile neutropenia, anaemia, neutropenia, sepsis, pneumonia, stomatitis and hypokalaemia. Overall <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>p rates were 29% and 32%; median overall survival (<jats:styled-content style=\"fixed-case\">OS<\/jats:styled-content>) was 7\u00b70\u00a0months; 1\u2010year <jats:styled-content style=\"fixed-case\">OS<\/jats:styled-content> was 34%. Schedule <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content> (72\u00a0mg\/m<jats:sup>2<\/jats:sup>) had the most favourable safety and efficacy profile, with faster haematological recovery (median 27\u00a0d) and lowest incidence of aggregate sepsis (24%) and 30\u2010d (7%) and 60\u2010d (17%) all\u2010cause mortality; at this dose and schedule, <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>p rates were 31% and 35%, median <jats:styled-content style=\"fixed-case\">OS<\/jats:styled-content> was 7\u00b77\u00a0months and 1\u2010year <jats:styled-content style=\"fixed-case\">OS<\/jats:styled-content> was 38%. Overall, vosaroxin resulted in low early mortality and an encouraging response rate; vosaroxin 72\u00a0mg\/m<jats:sup>2<\/jats:sup>\u00a0d 1, 4 is recommended for further study in this population. Registered at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">www.clinicaltrials.gov<\/jats:ext-link>: #<jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>00607997.<\/jats:p>","DOI":"10.1111\/bjh.13214","type":"journal-article","created":{"date-parts":[[2014,11,18]],"date-time":"2014-11-18T04:16:04Z","timestamp":1416284164000},"page":"796-805","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["<scp>REVEAL<\/scp>\u20101, a phase 2 dose regimen optimization study of vosaroxin in older poor\u2010risk patients with previously untreated acute myeloid leukaemia"],"prefix":"10.1111","volume":"168","author":[{"given":"Robert K.","family":"Stuart","sequence":"first","affiliation":[{"name":"Medical University of South Carolina Charleston SC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry D.","family":"Cripe","sequence":"additional","affiliation":[{"name":"Indiana University Cancer Center Indianapolis IN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael B.","family":"Maris","sequence":"additional","affiliation":[{"name":"Rocky Mountain Blood and Marrow Transplant Program Denver CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen A.","family":"Cooper","sequence":"additional","affiliation":[{"name":"St. Francis Hospital Indianapolis IN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard M.","family":"Stone","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber Cancer Institute Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaker R.","family":"Dakhil","sequence":"additional","affiliation":[{"name":"Cancer Center of Kansas Wichita KS USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Turturro","sequence":"additional","affiliation":[{"name":"Feist\u2010Weiller Cancer Center Louisiana State University Health Sciences Center Shreveport LA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy","family":"Stock","sequence":"additional","affiliation":[{"name":"University of Chicago Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Mason","sequence":"additional","affiliation":[{"name":"Scripps Cancer Center La Jolla CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J.","family":"Shami","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute University of Utah Salt Lake City UT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen A.","family":"Strickland","sequence":"additional","affiliation":[{"name":"Vanderbilt\u2010Ingram Cancer Center Nashville TN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciano J.","family":"Costa","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina Charleston SC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gautam","family":"Borthakur","sequence":"additional","affiliation":[{"name":"MD Anderson Cancer Center Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenn C.","family":"Michelson","sequence":"additional","affiliation":[{"name":"Sunesis Pharmaceuticals, Inc. 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