AustralieFrV1, Main, Exploration, bibRecord, 002648

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

Identifieur interne : 002648 ( Main/Exploration ); précédent : 002647; suivant : 002649

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

Auteurs : Farhad Ravandi ; Ellen K. Ritchie ; Hamid Sayar ; Jeffrey E. Lancet ; Michael D. Craig ; Norbert Vey ; Stephen A. Strickland ; Gary J. Schiller ; Elias Jabbour ; Harry P. Erba ; Arnaud Pigneux ; Heinz-August Horst ; Christian Recher ; Virginia M. Klimek ; Jorge Cortes ; Gail J. Roboz ; Olatoyosi Odenike ; Xavier Thomas ; Violaine Havelange ; Johan Maertens ; Hans-Günter Derigs ; Michael Heuser ; Lloyd Damon ; Bayard L. Powell ; Gianluca Gaidano ; Angelo-Michele Carella ; Andrew Wei ; Donna Hogge ; Adam R. Craig ; Judith A. Fox ; Renee Ward ; Jennifer A. Smith ; Gary Acton ; Cyrus Mehta ; Robert K. Stuart ; Hagop M. Kantarjian

Source :

The Lancet. Oncology [ 1470-2045 ] ; 2015.

RBID : PMC:4822512

Descripteurs français

KwdFr :
- Adulte, Adulte d'âge moyen, Cytarabine (administration et posologie), Estimation de Kaplan-Meier, Femelle, Humains, Induction de rémission, Leucémie aigüe myéloïde (anatomopathologie), Leucémie aigüe myéloïde (traitement médicamenteux), Mâle, Méthode en double aveugle, Naphtyridines (administration et posologie), Protocoles de polychimiothérapie antinéoplasique, Récidive tumorale locale (anatomopathologie), Récidive tumorale locale (traitement médicamenteux), Résultat thérapeutique, Sujet âgé, Sujet âgé de 80 ans ou plus, Survie sans rechute, Thiazoles (administration et posologie).
MESH :
- administration et posologie : Cytarabine, Naphtyridines, Thiazoles.
- anatomopathologie : Leucémie aigüe myéloïde, Récidive tumorale locale.
- traitement médicamenteux : Leucémie aigüe myéloïde, Récidive tumorale locale.
- Adulte, Adulte d'âge moyen, Estimation de Kaplan-Meier, Femelle, Humains, Induction de rémission, Mâle, Méthode en double aveugle, Protocoles de polychimiothérapie antinéoplasique, Résultat thérapeutique, Sujet âgé, Sujet âgé de 80 ans ou plus, Survie sans rechute.

English descriptors

KwdEn :
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Cytarabine (administration & dosage), Disease-Free Survival, Double-Blind Method, Female, Humans, Kaplan-Meier Estimate, Leukemia, Myeloid, Acute (drug therapy), Leukemia, Myeloid, Acute (pathology), Male, Middle Aged, Naphthyridines (administration & dosage), Neoplasm Recurrence, Local (drug therapy), Neoplasm Recurrence, Local (pathology), Remission Induction, Thiazoles (administration & dosage), Treatment Outcome.
MESH :
- chemical , administration & dosage : Cytarabine, Naphthyridines, Thiazoles.
- drug therapy : Leukemia, Myeloid, Acute, Neoplasm Recurrence, Local.
- pathology : Leukemia, Myeloid, Acute, Neoplasm Recurrence, Local.
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Disease-Free Survival, Double-Blind Method, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Remission Induction, Treatment Outcome.

Abstract

SummaryBackground

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.

Methods

VALOR was a phase 3, double-blind, placebo-controlled trial conducted at 101 international sites. Patients were randomised 1:1 to vosaroxin (90 mg/m² IV days 1,4) plus cytarabine (1 g/m² 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).

Findings

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 6·1 months with pla/cyt (hazard ratio 0·87; unstratified log-rank p=0·061; stratified p=0·0241) and was supported by a sensitivity analysis censoring for subsequent transplant (6·7 and 5·3 months; p=0·0243). Complete remission (CR) rate was higher with vos/cyt vs pla/cyt (30·1% vs 16·3%, p<0·0001). Early mortality rates were equivalent (vos/cyt vs pla/cyt: 30-day, 7·9% vs 6·6%; 60-day, 19·7% vs 19·4%). Treatment-related deaths occurred at any time in 18 patients (5·1%) with vos/cyt and 8 (2·3%) 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%]).

Interpretation

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.

Funding

Sunesis Pharmaceuticals

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822512

DOI: 10.1016/S1470-2045(15)00201-6
PubMed: 26234174
PubMed Central: 4822512

Affiliations:

Le document en format XML

<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>
<idno type="wicri:Area/Pmc/Curation">001C41</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001C41</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000C43</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000C43</idno>
<idno type="wicri:source">PubMed</idno>
<idno type="wicri:Area/PubMed/Corpus">002953</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002953</idno>
<idno type="wicri:Area/PubMed/Curation">002884</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002884</idno>
<idno type="wicri:Area/PubMed/Checkpoint">002884</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002884</idno>
<idno type="wicri:Area/Ncbi/Merge">002896</idno>
<idno type="wicri:Area/Ncbi/Curation">002896</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">002896</idno>
<idno type="wicri:doubleKey">1470-2045:2015:Ravandi F:vosaroxin:plus:cytarabine</idno>
<idno type="wicri:Area/Main/Merge">002647</idno>
<idno type="wicri:Area/Main/Curation">002648</idno>
<idno type="wicri:Area/Main/Exploration">002648</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><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Antineoplastic Combined Chemotherapy Protocols</term>
<term>Cytarabine (administration & dosage)</term>
<term>Disease-Free Survival</term>
<term>Double-Blind Method</term>
<term>Female</term>
<term>Humans</term>
<term>Kaplan-Meier Estimate</term>
<term>Leukemia, Myeloid, Acute (drug therapy)</term>
<term>Leukemia, Myeloid, Acute (pathology)</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Naphthyridines (administration & dosage)</term>
<term>Neoplasm Recurrence, Local (drug therapy)</term>
<term>Neoplasm Recurrence, Local (pathology)</term>
<term>Remission Induction</term>
<term>Thiazoles (administration & dosage)</term>
<term>Treatment Outcome</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Cytarabine (administration et posologie)</term>
<term>Estimation de Kaplan-Meier</term>
<term>Femelle</term>
<term>Humains</term>
<term>Induction de rémission</term>
<term>Leucémie aigüe myéloïde (anatomopathologie)</term>
<term>Leucémie aigüe myéloïde (traitement médicamenteux)</term>
<term>Mâle</term>
<term>Méthode en double aveugle</term>
<term>Naphtyridines (administration et posologie)</term>
<term>Protocoles de polychimiothérapie antinéoplasique</term>
<term>Récidive tumorale locale (anatomopathologie)</term>
<term>Récidive tumorale locale (traitement médicamenteux)</term>
<term>Résultat thérapeutique</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>Survie sans rechute</term>
<term>Thiazoles (administration et posologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Cytarabine</term>
<term>Naphthyridines</term>
<term>Thiazoles</term>
</keywords>
<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Cytarabine</term>
<term>Naphtyridines</term>
<term>Thiazoles</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Leucémie aigüe myéloïde</term>
<term>Récidive tumorale locale</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Leukemia, Myeloid, Acute</term>
<term>Neoplasm Recurrence, Local</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Leukemia, Myeloid, Acute</term>
<term>Neoplasm Recurrence, Local</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Leucémie aigüe myéloïde</term>
<term>Récidive tumorale locale</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Antineoplastic Combined Chemotherapy Protocols</term>
<term>Disease-Free Survival</term>
<term>Double-Blind Method</term>
<term>Female</term>
<term>Humans</term>
<term>Kaplan-Meier Estimate</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Remission Induction</term>
<term>Treatment Outcome</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Estimation de Kaplan-Meier</term>
<term>Femelle</term>
<term>Humains</term>
<term>Induction de rémission</term>
<term>Mâle</term>
<term>Méthode en double aveugle</term>
<term>Protocoles de polychimiothérapie antinéoplasique</term>
<term>Résultat thérapeutique</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>Survie sans rechute</term>
</keywords>
</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>
<affiliations><list></list>
<tree><noCountry><name sortKey="Acton, Gary" sort="Acton, Gary" uniqKey="Acton G" first="Gary" last="Acton">Gary Acton</name>
<name sortKey="Carella, Angelo Michele" sort="Carella, Angelo Michele" uniqKey="Carella A" first="Angelo-Michele" last="Carella">Angelo-Michele Carella</name>
<name sortKey="Cortes, Jorge" sort="Cortes, Jorge" uniqKey="Cortes J" first="Jorge" last="Cortes">Jorge Cortes</name>
<name sortKey="Craig, Adam R" sort="Craig, Adam R" uniqKey="Craig A" first="Adam R." last="Craig">Adam R. Craig</name>
<name sortKey="Craig, Michael D" sort="Craig, Michael D" uniqKey="Craig M" first="Michael D." last="Craig">Michael D. Craig</name>
<name sortKey="Damon, Lloyd" sort="Damon, Lloyd" uniqKey="Damon L" first="Lloyd" last="Damon">Lloyd Damon</name>
<name sortKey="Derigs, Hans Gunter" sort="Derigs, Hans Gunter" uniqKey="Derigs H" first="Hans-Günter" last="Derigs">Hans-Günter Derigs</name>
<name sortKey="Erba, Harry P" sort="Erba, Harry P" uniqKey="Erba H" first="Harry P." last="Erba">Harry P. Erba</name>
<name sortKey="Fox, Judith A" sort="Fox, Judith A" uniqKey="Fox J" first="Judith A." last="Fox">Judith A. Fox</name>
<name sortKey="Gaidano, Gianluca" sort="Gaidano, Gianluca" uniqKey="Gaidano G" first="Gianluca" last="Gaidano">Gianluca Gaidano</name>
<name sortKey="Havelange, Violaine" sort="Havelange, Violaine" uniqKey="Havelange V" first="Violaine" last="Havelange">Violaine Havelange</name>
<name sortKey="Heuser, Michael" sort="Heuser, Michael" uniqKey="Heuser M" first="Michael" last="Heuser">Michael Heuser</name>
<name sortKey="Hogge, Donna" sort="Hogge, Donna" uniqKey="Hogge D" first="Donna" last="Hogge">Donna Hogge</name>
<name sortKey="Horst, Heinz August" sort="Horst, Heinz August" uniqKey="Horst H" first="Heinz-August" last="Horst">Heinz-August Horst</name>
<name sortKey="Jabbour, Elias" sort="Jabbour, Elias" uniqKey="Jabbour E" first="Elias" last="Jabbour">Elias Jabbour</name>
<name sortKey="Kantarjian, Hagop M" sort="Kantarjian, Hagop M" uniqKey="Kantarjian H" first="Hagop M." last="Kantarjian">Hagop M. Kantarjian</name>
<name sortKey="Klimek, Virginia M" sort="Klimek, Virginia M" uniqKey="Klimek V" first="Virginia M." last="Klimek">Virginia M. Klimek</name>
<name sortKey="Lancet, Jeffrey E" sort="Lancet, Jeffrey E" uniqKey="Lancet J" first="Jeffrey E." last="Lancet">Jeffrey E. Lancet</name>
<name sortKey="Maertens, Johan" sort="Maertens, Johan" uniqKey="Maertens J" first="Johan" last="Maertens">Johan Maertens</name>
<name sortKey="Mehta, Cyrus" sort="Mehta, Cyrus" uniqKey="Mehta C" first="Cyrus" last="Mehta">Cyrus Mehta</name>
<name sortKey="Odenike, Olatoyosi" sort="Odenike, Olatoyosi" uniqKey="Odenike O" first="Olatoyosi" last="Odenike">Olatoyosi Odenike</name>
<name sortKey="Pigneux, Arnaud" sort="Pigneux, Arnaud" uniqKey="Pigneux A" first="Arnaud" last="Pigneux">Arnaud Pigneux</name>
<name sortKey="Powell, Bayard L" sort="Powell, Bayard L" uniqKey="Powell B" first="Bayard L." last="Powell">Bayard L. Powell</name>
<name sortKey="Ravandi, Farhad" sort="Ravandi, Farhad" uniqKey="Ravandi F" first="Farhad" last="Ravandi">Farhad Ravandi</name>
<name sortKey="Recher, Christian" sort="Recher, Christian" uniqKey="Recher C" first="Christian" last="Recher">Christian Recher</name>
<name sortKey="Ritchie, Ellen K" sort="Ritchie, Ellen K" uniqKey="Ritchie E" first="Ellen K." last="Ritchie">Ellen K. Ritchie</name>
<name sortKey="Roboz, Gail J" sort="Roboz, Gail J" uniqKey="Roboz G" first="Gail J." last="Roboz">Gail J. Roboz</name>
<name sortKey="Sayar, Hamid" sort="Sayar, Hamid" uniqKey="Sayar H" first="Hamid" last="Sayar">Hamid Sayar</name>
<name sortKey="Schiller, Gary J" sort="Schiller, Gary J" uniqKey="Schiller G" first="Gary J." last="Schiller">Gary J. Schiller</name>
<name sortKey="Smith, Jennifer A" sort="Smith, Jennifer A" uniqKey="Smith J" first="Jennifer A." last="Smith">Jennifer A. Smith</name>
<name sortKey="Strickland, Stephen A" sort="Strickland, Stephen A" uniqKey="Strickland S" first="Stephen A." last="Strickland">Stephen A. Strickland</name>
<name sortKey="Stuart, Robert K" sort="Stuart, Robert K" uniqKey="Stuart R" first="Robert K." last="Stuart">Robert K. Stuart</name>
<name sortKey="Thomas, Xavier" sort="Thomas, Xavier" uniqKey="Thomas X" first="Xavier" last="Thomas">Xavier Thomas</name>
<name sortKey="Vey, Norbert" sort="Vey, Norbert" uniqKey="Vey N" first="Norbert" last="Vey">Norbert Vey</name>
<name sortKey="Ward, Renee" sort="Ward, Renee" uniqKey="Ward R" first="Renee" last="Ward">Renee Ward</name>
<name sortKey="Wei, Andrew" sort="Wei, Andrew" uniqKey="Wei A" first="Andrew" last="Wei">Andrew Wei</name>
</noCountry>
</tree>
</affiliations>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Main/Exploration

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002648 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 002648 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Wicri/Asie
   |area=    AustralieFrV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     PMC:4822512
   |texte=   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
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:26234174" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a AustralieFrV1

This area was generated with Dilib version V0.6.33.
Data generation: Tue Dec 5 10:43:12 2017. Site generation: Tue Mar 5 14:07:20 2024

Serveur d'exploration sur les relations entre la France et l'Australie

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

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

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki

	Serveur d'exploration sur les relations entre la France et l'Australie
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.