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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study</title><author><name sortKey="Ravandi, Farhad" sort="Ravandi, Farhad" uniqKey="Ravandi F" first="Farhad" last="Ravandi">Farhad Ravandi</name></author><author><name sortKey="Ritchie, Ellen K" sort="Ritchie, Ellen K" uniqKey="Ritchie E" first="Ellen K." last="Ritchie">Ellen K. Ritchie</name></author><author><name sortKey="Sayar, Hamid" sort="Sayar, Hamid" uniqKey="Sayar H" first="Hamid" last="Sayar">Hamid Sayar</name></author><author><name sortKey="Lancet, Jeffrey E" sort="Lancet, Jeffrey E" uniqKey="Lancet J" first="Jeffrey E." last="Lancet">Jeffrey E. Lancet</name></author><author><name sortKey="Craig, Michael D" sort="Craig, Michael D" uniqKey="Craig M" first="Michael D." last="Craig">Michael D. Craig</name></author><author><name sortKey="Vey, Norbert" sort="Vey, Norbert" uniqKey="Vey N" first="Norbert" last="Vey">Norbert Vey</name></author><author><name sortKey="Strickland, Stephen A" sort="Strickland, Stephen A" uniqKey="Strickland S" first="Stephen A." last="Strickland">Stephen A. Strickland</name></author><author><name sortKey="Schiller, Gary J" sort="Schiller, Gary J" uniqKey="Schiller G" first="Gary J." last="Schiller">Gary J. Schiller</name></author><author><name sortKey="Jabbour, Elias" sort="Jabbour, Elias" uniqKey="Jabbour E" first="Elias" last="Jabbour">Elias Jabbour</name></author><author><name sortKey="Erba, Harry P" sort="Erba, Harry P" uniqKey="Erba H" first="Harry P." last="Erba">Harry P. Erba</name></author><author><name sortKey="Pigneux, Arnaud" sort="Pigneux, Arnaud" uniqKey="Pigneux A" first="Arnaud" last="Pigneux">Arnaud Pigneux</name></author><author><name sortKey="Horst, Heinz August" sort="Horst, Heinz August" uniqKey="Horst H" first="Heinz-August" last="Horst">Heinz-August Horst</name></author><author><name sortKey="Recher, Christian" sort="Recher, Christian" uniqKey="Recher C" first="Christian" last="Recher">Christian Recher</name></author><author><name sortKey="Klimek, Virginia M" sort="Klimek, Virginia M" uniqKey="Klimek V" first="Virginia M." last="Klimek">Virginia M. Klimek</name></author><author><name sortKey="Cortes, Jorge" sort="Cortes, Jorge" uniqKey="Cortes J" first="Jorge" last="Cortes">Jorge Cortes</name></author><author><name sortKey="Roboz, Gail J" sort="Roboz, Gail J" uniqKey="Roboz G" first="Gail J." last="Roboz">Gail J. Roboz</name></author><author><name sortKey="Odenike, Olatoyosi" sort="Odenike, Olatoyosi" uniqKey="Odenike O" first="Olatoyosi" last="Odenike">Olatoyosi Odenike</name></author><author><name sortKey="Thomas, Xavier" sort="Thomas, Xavier" uniqKey="Thomas X" first="Xavier" last="Thomas">Xavier Thomas</name></author><author><name sortKey="Havelange, Violaine" sort="Havelange, Violaine" uniqKey="Havelange V" first="Violaine" last="Havelange">Violaine Havelange</name></author><author><name sortKey="Maertens, Johan" sort="Maertens, Johan" uniqKey="Maertens J" first="Johan" last="Maertens">Johan Maertens</name></author><author><name sortKey="Derigs, Hans Gunter" sort="Derigs, Hans Gunter" uniqKey="Derigs H" first="Hans-Günter" last="Derigs">Hans-Günter Derigs</name></author><author><name sortKey="Heuser, Michael" sort="Heuser, Michael" uniqKey="Heuser M" first="Michael" last="Heuser">Michael Heuser</name></author><author><name sortKey="Damon, Lloyd" sort="Damon, Lloyd" uniqKey="Damon L" first="Lloyd" last="Damon">Lloyd Damon</name></author><author><name sortKey="Powell, Bayard L" sort="Powell, Bayard L" uniqKey="Powell B" first="Bayard L." last="Powell">Bayard L. Powell</name></author><author><name sortKey="Gaidano, Gianluca" sort="Gaidano, Gianluca" uniqKey="Gaidano G" first="Gianluca" last="Gaidano">Gianluca Gaidano</name></author><author><name sortKey="Carella, Angelo Michele" sort="Carella, Angelo Michele" uniqKey="Carella A" first="Angelo-Michele" last="Carella">Angelo-Michele Carella</name></author><author><name sortKey="Wei, Andrew" sort="Wei, Andrew" uniqKey="Wei A" first="Andrew" last="Wei">Andrew Wei</name></author><author><name sortKey="Hogge, Donna" sort="Hogge, Donna" uniqKey="Hogge D" first="Donna" last="Hogge">Donna Hogge</name></author><author><name sortKey="Craig, Adam R" sort="Craig, Adam R" uniqKey="Craig A" first="Adam R." last="Craig">Adam R. Craig</name></author><author><name sortKey="Fox, Judith A" sort="Fox, Judith A" uniqKey="Fox J" first="Judith A." last="Fox">Judith A. Fox</name></author><author><name sortKey="Ward, Renee" sort="Ward, Renee" uniqKey="Ward R" first="Renee" last="Ward">Renee Ward</name></author><author><name sortKey="Smith, Jennifer A" sort="Smith, Jennifer A" uniqKey="Smith J" first="Jennifer A." last="Smith">Jennifer A. Smith</name></author><author><name sortKey="Acton, Gary" sort="Acton, Gary" uniqKey="Acton G" first="Gary" last="Acton">Gary Acton</name></author><author><name sortKey="Mehta, Cyrus" sort="Mehta, Cyrus" uniqKey="Mehta C" first="Cyrus" last="Mehta">Cyrus Mehta</name></author><author><name sortKey="Stuart, Robert K" sort="Stuart, Robert K" uniqKey="Stuart R" first="Robert K." last="Stuart">Robert K. Stuart</name></author><author><name sortKey="Kantarjian, Hagop M" sort="Kantarjian, Hagop M" uniqKey="Kantarjian H" first="Hagop M." last="Kantarjian">Hagop M. Kantarjian</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26234174</idno><idno type="pmc">4822512</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822512</idno><idno type="RBID">PMC:4822512</idno><idno type="doi">10.1016/S1470-2045(15)00201-6</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">001D85</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001D85</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study</title><author><name sortKey="Ravandi, Farhad" sort="Ravandi, Farhad" uniqKey="Ravandi F" first="Farhad" last="Ravandi">Farhad Ravandi</name></author><author><name sortKey="Ritchie, Ellen K" sort="Ritchie, Ellen K" uniqKey="Ritchie E" first="Ellen K." last="Ritchie">Ellen K. Ritchie</name></author><author><name sortKey="Sayar, Hamid" sort="Sayar, Hamid" uniqKey="Sayar H" first="Hamid" last="Sayar">Hamid Sayar</name></author><author><name sortKey="Lancet, Jeffrey E" sort="Lancet, Jeffrey E" uniqKey="Lancet J" first="Jeffrey E." last="Lancet">Jeffrey E. Lancet</name></author><author><name sortKey="Craig, Michael D" sort="Craig, Michael D" uniqKey="Craig M" first="Michael D." last="Craig">Michael D. Craig</name></author><author><name sortKey="Vey, Norbert" sort="Vey, Norbert" uniqKey="Vey N" first="Norbert" last="Vey">Norbert Vey</name></author><author><name sortKey="Strickland, Stephen A" sort="Strickland, Stephen A" uniqKey="Strickland S" first="Stephen A." last="Strickland">Stephen A. Strickland</name></author><author><name sortKey="Schiller, Gary J" sort="Schiller, Gary J" uniqKey="Schiller G" first="Gary J." last="Schiller">Gary J. Schiller</name></author><author><name sortKey="Jabbour, Elias" sort="Jabbour, Elias" uniqKey="Jabbour E" first="Elias" last="Jabbour">Elias Jabbour</name></author><author><name sortKey="Erba, Harry P" sort="Erba, Harry P" uniqKey="Erba H" first="Harry P." last="Erba">Harry P. Erba</name></author><author><name sortKey="Pigneux, Arnaud" sort="Pigneux, Arnaud" uniqKey="Pigneux A" first="Arnaud" last="Pigneux">Arnaud Pigneux</name></author><author><name sortKey="Horst, Heinz August" sort="Horst, Heinz August" uniqKey="Horst H" first="Heinz-August" last="Horst">Heinz-August Horst</name></author><author><name sortKey="Recher, Christian" sort="Recher, Christian" uniqKey="Recher C" first="Christian" last="Recher">Christian Recher</name></author><author><name sortKey="Klimek, Virginia M" sort="Klimek, Virginia M" uniqKey="Klimek V" first="Virginia M." last="Klimek">Virginia M. Klimek</name></author><author><name sortKey="Cortes, Jorge" sort="Cortes, Jorge" uniqKey="Cortes J" first="Jorge" last="Cortes">Jorge Cortes</name></author><author><name sortKey="Roboz, Gail J" sort="Roboz, Gail J" uniqKey="Roboz G" first="Gail J." last="Roboz">Gail J. Roboz</name></author><author><name sortKey="Odenike, Olatoyosi" sort="Odenike, Olatoyosi" uniqKey="Odenike O" first="Olatoyosi" last="Odenike">Olatoyosi Odenike</name></author><author><name sortKey="Thomas, Xavier" sort="Thomas, Xavier" uniqKey="Thomas X" first="Xavier" last="Thomas">Xavier Thomas</name></author><author><name sortKey="Havelange, Violaine" sort="Havelange, Violaine" uniqKey="Havelange V" first="Violaine" last="Havelange">Violaine Havelange</name></author><author><name sortKey="Maertens, Johan" sort="Maertens, Johan" uniqKey="Maertens J" first="Johan" last="Maertens">Johan Maertens</name></author><author><name sortKey="Derigs, Hans Gunter" sort="Derigs, Hans Gunter" uniqKey="Derigs H" first="Hans-Günter" last="Derigs">Hans-Günter Derigs</name></author><author><name sortKey="Heuser, Michael" sort="Heuser, Michael" uniqKey="Heuser M" first="Michael" last="Heuser">Michael Heuser</name></author><author><name sortKey="Damon, Lloyd" sort="Damon, Lloyd" uniqKey="Damon L" first="Lloyd" last="Damon">Lloyd Damon</name></author><author><name sortKey="Powell, Bayard L" sort="Powell, Bayard L" uniqKey="Powell B" first="Bayard L." last="Powell">Bayard L. Powell</name></author><author><name sortKey="Gaidano, Gianluca" sort="Gaidano, Gianluca" uniqKey="Gaidano G" first="Gianluca" last="Gaidano">Gianluca Gaidano</name></author><author><name sortKey="Carella, Angelo Michele" sort="Carella, Angelo Michele" uniqKey="Carella A" first="Angelo-Michele" last="Carella">Angelo-Michele Carella</name></author><author><name sortKey="Wei, Andrew" sort="Wei, Andrew" uniqKey="Wei A" first="Andrew" last="Wei">Andrew Wei</name></author><author><name sortKey="Hogge, Donna" sort="Hogge, Donna" uniqKey="Hogge D" first="Donna" last="Hogge">Donna Hogge</name></author><author><name sortKey="Craig, Adam R" sort="Craig, Adam R" uniqKey="Craig A" first="Adam R." last="Craig">Adam R. Craig</name></author><author><name sortKey="Fox, Judith A" sort="Fox, Judith A" uniqKey="Fox J" first="Judith A." last="Fox">Judith A. Fox</name></author><author><name sortKey="Ward, Renee" sort="Ward, Renee" uniqKey="Ward R" first="Renee" last="Ward">Renee Ward</name></author><author><name sortKey="Smith, Jennifer A" sort="Smith, Jennifer A" uniqKey="Smith J" first="Jennifer A." last="Smith">Jennifer A. Smith</name></author><author><name sortKey="Acton, Gary" sort="Acton, Gary" uniqKey="Acton G" first="Gary" last="Acton">Gary Acton</name></author><author><name sortKey="Mehta, Cyrus" sort="Mehta, Cyrus" uniqKey="Mehta C" first="Cyrus" last="Mehta">Cyrus Mehta</name></author><author><name sortKey="Stuart, Robert K" sort="Stuart, Robert K" uniqKey="Stuart R" first="Robert K." last="Stuart">Robert K. Stuart</name></author><author><name sortKey="Kantarjian, Hagop M" sort="Kantarjian, Hagop M" uniqKey="Kantarjian H" first="Hagop M." last="Kantarjian">Hagop M. Kantarjian</name></author></analytic><series><title level="j">The Lancet. Oncology</title><idno type="ISSN">1470-2045</idno><idno type="eISSN">1474-5488</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><sec id="S2"><title>Background</title><p id="P1">Safe and effective treatments are urgently needed for patients with relapsed/refractory acute myeloid leukaemia (AML). We investigated the efficacy and safety of vosaroxin, a first-in-class anticancer quinolone derivative, plus cytarabine in patients with relapsed/refractory AML.</p></sec><sec id="S3"><title>Methods</title><p id="P2">VALOR was a phase 3, double-blind, placebo-controlled trial conducted at 101 international sites. Patients were randomised 1:1 to vosaroxin (90 mg/m<sup>2</sup> IV days 1,4) plus cytarabine (1 g/m<sup>2</sup> IV days 1–5) (vos/cyt) or placebo plus cytarabine (pla/cyt) using a permuted block procedure stratified by disease status, age, and geographic location. All participants were blind to treatment assignment. Primary endpoints were overall survival (OS) and 30- and 60-day mortality. Efficacy analyses were by intention-to-treat; safety analyses included all treated patients. This study is registered at clinicaltrials.gov (NCT01191801).</p></sec><sec id="S4"><title>Findings</title><p id="P3">Between December 2010 and September 2013, 711 patients were randomised to vos/cyt (n=356) or pla/cyt (n=355). Median OS was 7·5 months with vos/cyt and 6<bold>·</bold>1 months with pla/cyt (hazard ratio 0<bold>·</bold>87; unstratified log-rank p=0<bold>·</bold>061; stratified p=0<bold>·</bold>0241) and was supported by a sensitivity analysis censoring for subsequent transplant (6<bold>·</bold>7 and 5<bold>·</bold>3 months; p=0<bold>·</bold>0243). Complete remission (CR) rate was higher with vos/cyt vs pla/cyt (30<bold>·</bold>1% vs 16<bold>·</bold>3%, p<0<bold>·</bold>0001). Early mortality rates were equivalent (vos/cyt vs pla/cyt: 30-day, 7<bold>·</bold>9% vs 6<bold>·</bold>6%; 60-day, 19<bold>·</bold>7% vs 19<bold>·</bold>4%). Treatment-related deaths occurred at any time in 18 patients (5<bold>·</bold>1%) with vos/cyt and 8 (2<bold>·</bold>3%) with pla/cyt. Grade ≥3 adverse events more frequent with vos/cyt included febrile neutropenia (167/355 [47%] vs 117/350 [33%]), stomatitis (54 [15%] vs 10 [3%]), hypokalaemia (52 [15%] vs 21 [6%]), sepsis (42 [12%] vs 18 [5%]), and pneumonia (39 [11%] vs 26 [7%]).</p></sec><sec id="S5"><title>Interpretation</title><p id="P4">Addition of vosaroxin to cytarabine prolonged survival in patients with relapsed/refractory AML, increasing CR rates with equivalent early mortality. These results support vos/cyt as an option for salvage therapy in AML patients.</p></sec><sec id="S6"><title>Funding</title><p id="P5">Sunesis Pharmaceuticals</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">100957246</journal-id><journal-id journal-id-type="pubmed-jr-id">27004</journal-id><journal-id journal-id-type="nlm-ta">Lancet Oncol</journal-id><journal-id journal-id-type="iso-abbrev">Lancet Oncol.</journal-id><journal-title-group><journal-title>The Lancet. Oncology</journal-title></journal-title-group><issn pub-type="ppub">1470-2045</issn><issn pub-type="epub">1474-5488</issn></journal-meta><article-meta><article-id pub-id-type="pmid">26234174</article-id><article-id pub-id-type="pmc">4822512</article-id><article-id pub-id-type="doi">10.1016/S1470-2045(15)00201-6</article-id><article-id pub-id-type="manuscript">NIHMS769284</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Ravandi</surname><given-names>Farhad</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Ritchie</surname><given-names>Ellen K.</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Sayar</surname><given-names>Hamid</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Lancet</surname><given-names>Jeffrey E.</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Craig</surname><given-names>Michael D.</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Vey</surname><given-names>Norbert</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Strickland</surname><given-names>Stephen A.</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Schiller</surname><given-names>Gary J.</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Jabbour</surname><given-names>Elias</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Erba</surname><given-names>Harry P.</given-names></name><degrees>MD, PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Pigneux</surname><given-names>Arnaud</given-names></name><degrees>MD, PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Horst</surname><given-names>Heinz-August</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Recher</surname><given-names>Christian</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Klimek</surname><given-names>Virginia M.</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Cortes</surname><given-names>Jorge</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Roboz</surname><given-names>Gail J.</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Odenike</surname><given-names>Olatoyosi</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Thomas</surname><given-names>Xavier</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Havelange</surname><given-names>Violaine</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Maertens</surname><given-names>Johan</given-names></name><degrees>MD, PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Derigs</surname><given-names>Hans-Günter</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Heuser</surname><given-names>Michael</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Damon</surname><given-names>Lloyd</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Powell</surname><given-names>Bayard L.</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Gaidano</surname><given-names>Gianluca</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Carella</surname><given-names>Angelo-Michele</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Wei</surname><given-names>Andrew</given-names></name><degrees>MBBS, PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Hogge</surname><given-names>Donna</given-names></name><degrees>MD, PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Craig</surname><given-names>Adam R.</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Fox</surname><given-names>Judith A.</given-names></name><degrees>PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Ward</surname><given-names>Renee</given-names></name><degrees>MD, PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Smith</surname><given-names>Jennifer A.</given-names></name><degrees>PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Acton</surname><given-names>Gary</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Mehta</surname><given-names>Cyrus</given-names></name><degrees>PhD</degrees></contrib><contrib contrib-type="author"><name><surname>Stuart</surname><given-names>Robert K.</given-names></name><degrees>MD</degrees></contrib><contrib contrib-type="author"><name><surname>Kantarjian</surname><given-names>Hagop M.</given-names></name><degrees>MD</degrees></contrib><aff id="A1">University of Texas MD Anderson Cancer Center, Houston, TX (F Ravandi MD, E Jabbour MD, J Cortes MD, HM Kantarjian MD); Weill Cornell Medical Center, New York, NY (EK Ritchie MD, GJ Roboz MD); Indiana University Cancer Center, Indianapolis, IN (H Sayar MD); Moffitt Cancer Center, Tampa, FL (JE Lancet MD); West Virginia University, Morgantown, WV (MD Craig MD); Institut Paoli-Calmettes and Aix-Marseille University, Marseille, France (N Vey MD); Vanderbilt-Ingram Cancer Center, Nashville, TN (SA Strickland MD); University of California, Los Angeles, CA (GJ Schiller MD); Division of Hematology and Oncology, University of Alabama, Birmingham, AL (HP Erba MD, PhD); Université de Bordeaux, CHU de Bordeaux, Bordeaux, France (A Pigneux MD, PhD); II. Medizinische Klinik und Poliklinik im Städtischen Krankenhaus, Kiel, Germany (H-A Horst MD); Institut Universitaire du Cancer de Toulouse Oncopole, Université de Toulouse III, CHU de Toulouse, Toulouse, France (C Recher MD); Memorial Sloan-Kettering Cancer Center, New York, NY (VM Klimek MD); University of Chicago, Chicago, IL (O Odenike MD); Hôpital Edouard Herriot, Lyon, France (X Thomas MD); Cliniques Universitaires Saint-Luc, Brussels, Belgium (V Havelange MD); Universitair Ziekenhuis, Leuven, Belgium (J Maertens MD, PhD); Klinikum Frankfurt Main, Frankfurt, Germany (H-G Derigs MD); Hannover Medical School, Hannover, Germany (M Heuser MD); UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA (L Damon MD); Wake Forest University Baptist Medical Center - Comprehensive Cancer Center, Winston-Salem, NC (BL Powell MD); Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy (G Gaidano MD); IRCCS AOU San Martino-IST, Genoa, Italy (A-M Carella MD); The Alfred Hospital and Monash University, Melbourne, VIC, Australia (A Wei MBBS, PhD); Vancouver General Hospital, Vancouver, BC, Canada (D Hogge MD, PhD); Sunesis Pharmaceuticals, Inc., South San Francisco, CA (AR Craig MD, JA Fox PhD, R Ward MD, PhD, JA Smith PhD, G Acton MD); Cytel, Inc. and Harvard School of Public Health, Cambridge, MA (C Mehta PhD); Medical University of South Carolina, Charleston, SC (RK Stuart MD)</aff></contrib-group><author-notes><corresp id="FN1">Corresponding Author: Farhad Ravandi, MD, MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, Phone: (713) 792-2121, <email>fravandi@mdanderson.org</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>27</day><month>3</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>30</day><month>7</month><year>2015</year></pub-date><pub-date pub-type="ppub"><month>9</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>9</month><year>2016</year></pub-date><volume>16</volume><issue>9</issue><fpage>1025</fpage><lpage>1036</lpage><pmc-comment>elocation-id from pubmed: 10.1016/S1470-2045(15)00201-6</pmc-comment>
<abstract><title>Summary</title><sec id="S2"><title>Background</title><p id="P1">Safe and effective treatments are urgently needed for patients with relapsed/refractory acute myeloid leukaemia (AML). We investigated the efficacy and safety of vosaroxin, a first-in-class anticancer quinolone derivative, plus cytarabine in patients with relapsed/refractory AML.</p></sec><sec id="S3"><title>Methods</title><p id="P2">VALOR was a phase 3, double-blind, placebo-controlled trial conducted at 101 international sites. Patients were randomised 1:1 to vosaroxin (90 mg/m<sup>2</sup> IV days 1,4) plus cytarabine (1 g/m<sup>2</sup> IV days 1–5) (vos/cyt) or placebo plus cytarabine (pla/cyt) using a permuted block procedure stratified by disease status, age, and geographic location. All participants were blind to treatment assignment. Primary endpoints were overall survival (OS) and 30- and 60-day mortality. Efficacy analyses were by intention-to-treat; safety analyses included all treated patients. This study is registered at clinicaltrials.gov (NCT01191801).</p></sec><sec id="S4"><title>Findings</title><p id="P3">Between December 2010 and September 2013, 711 patients were randomised to vos/cyt (n=356) or pla/cyt (n=355). Median OS was 7·5 months with vos/cyt and 6<bold>·</bold>1 months with pla/cyt (hazard ratio 0<bold>·</bold>87; unstratified log-rank p=0<bold>·</bold>061; stratified p=0<bold>·</bold>0241) and was supported by a sensitivity analysis censoring for subsequent transplant (6<bold>·</bold>7 and 5<bold>·</bold>3 months; p=0<bold>·</bold>0243). Complete remission (CR) rate was higher with vos/cyt vs pla/cyt (30<bold>·</bold>1% vs 16<bold>·</bold>3%, p<0<bold>·</bold>0001). Early mortality rates were equivalent (vos/cyt vs pla/cyt: 30-day, 7<bold>·</bold>9% vs 6<bold>·</bold>6%; 60-day, 19<bold>·</bold>7% vs 19<bold>·</bold>4%). Treatment-related deaths occurred at any time in 18 patients (5<bold>·</bold>1%) with vos/cyt and 8 (2<bold>·</bold>3%) with pla/cyt. Grade ≥3 adverse events more frequent with vos/cyt included febrile neutropenia (167/355 [47%] vs 117/350 [33%]), stomatitis (54 [15%] vs 10 [3%]), hypokalaemia (52 [15%] vs 21 [6%]), sepsis (42 [12%] vs 18 [5%]), and pneumonia (39 [11%] vs 26 [7%]).</p></sec><sec id="S5"><title>Interpretation</title><p id="P4">Addition of vosaroxin to cytarabine prolonged survival in patients with relapsed/refractory AML, increasing CR rates with equivalent early mortality. These results support vos/cyt as an option for salvage therapy in AML patients.</p></sec><sec id="S6"><title>Funding</title><p id="P5">Sunesis Pharmaceuticals</p></sec></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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