Denosumab for the prevention of skeletal complications in metastatic castration-resistant prostate cancer: comparison of skeletal-related events and symptomatic skeletal events.
Identifieur interne : 002F47 ( PubMed/Curation ); précédent : 002F46; suivant : 002F48Denosumab for the prevention of skeletal complications in metastatic castration-resistant prostate cancer: comparison of skeletal-related events and symptomatic skeletal events.
Auteurs : M R Smith [États-Unis] ; R E Coleman [Royaume-Uni] ; L. Klotz [Canada] ; K. Pittman [Australie] ; P. Milecki [Pologne] ; S. Ng [Australie] ; K N Chi [Canada] ; A. Balakumaran ; R. Wei [États-Unis] ; H. Wang [États-Unis] ; A. Braun ; K. Fizazi [France]Source :
- Annals of oncology : official journal of the European Society for Medical Oncology [ 1569-8041 ] ; 2015.
Descripteurs français
- KwdFr :
- MESH :
- anatomopathologie : Tumeurs prostatiques résistantes à la castration.
- secondaire : Tumeurs osseuses.
- usage thérapeutique : Agents de maintien de la densité osseuse, Dénosumab.
- Adulte d'âge moyen, Humains, Mâle, Méthode en double aveugle, Sujet âgé, Tumeurs osseuses.
English descriptors
- KwdEn :
- MESH :
- chemical , therapeutic use : Bone Density Conservation Agents, Denosumab.
- complications : Bone Neoplasms.
- pathology : Prostatic Neoplasms, Castration-Resistant.
- secondary : Bone Neoplasms.
- Aged, Double-Blind Method, Humans, Male, Middle Aged.
Abstract
In a phase III trial in patients with castration-resistant prostate cancer (CRPC) and bone metastases, denosumab was superior to zoledronic acid in reducing skeletal-related events (SREs; radiation to bone, pathologic fracture, surgery to bone, or spinal cord compression). This study reassessed the efficacy of denosumab using symptomatic skeletal events (SSEs) as a prespecified exploratory end point.
DOI: 10.1093/annonc/mdu519
PubMed: 25425475
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A. Balakumaran<affiliation><nlm:affiliation>Department of Hematology/Oncology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Hematology/Oncology.</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Department of Hematology/Oncology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Hematology/Oncology.</wicri:noCountry></affiliation>Le document en format XML
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Balakumaran</name><affiliation><nlm:affiliation>Department of Hematology/Oncology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Hematology/Oncology.</wicri:noCountry></affiliation></author><author><name sortKey="Wei, R" sort="Wei, R" uniqKey="Wei R" first="R" last="Wei">R. Wei</name><affiliation wicri:level="1"><nlm:affiliation>Global Biostatistical Science, Amgen Inc., Thousand Oaks, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Global Biostatistical Science, Amgen Inc., Thousand Oaks</wicri:regionArea></affiliation></author><author><name sortKey="Wang, H" sort="Wang, H" uniqKey="Wang H" first="H" last="Wang">H. Wang</name><affiliation wicri:level="1"><nlm:affiliation>Global Biostatistical Science, Amgen Inc., Thousand Oaks, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Global Biostatistical Science, Amgen Inc., Thousand Oaks</wicri:regionArea></affiliation></author><author><name sortKey="Braun, A" sort="Braun, A" uniqKey="Braun A" first="A" last="Braun">A. Braun</name><affiliation><nlm:affiliation>Department of Hematology/Oncology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Hematology/Oncology.</wicri:noCountry></affiliation></author><author><name sortKey="Fizazi, K" sort="Fizazi, K" uniqKey="Fizazi K" first="K" last="Fizazi">K. Fizazi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Oncology, Institut Gustave Roussy, University of Paris Sud, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Oncology, Institut Gustave Roussy, University of Paris Sud, Paris</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:25425475</idno><idno type="pmid">25425475</idno><idno type="doi">10.1093/annonc/mdu519</idno><idno type="wicri:Area/PubMed/Corpus">003028</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">003028</idno><idno type="wicri:Area/PubMed/Curation">002F47</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002F47</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Denosumab for the prevention of skeletal complications in metastatic castration-resistant prostate cancer: comparison of skeletal-related events and symptomatic skeletal events.</title><author><name sortKey="Smith, M R" sort="Smith, M R" uniqKey="Smith M" first="M R" last="Smith">M R Smith</name><affiliation wicri:level="1"><nlm:affiliation>Department of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Boston, USA smith.matthew@mgh.harvard.edu.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>Department of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Boston</wicri:regionArea></affiliation></author><author><name sortKey="Coleman, R E" sort="Coleman, R E" uniqKey="Coleman R" first="R E" last="Coleman">R E Coleman</name><affiliation wicri:level="1"><nlm:affiliation>Academic Unit of Clinical Oncology, Sheffield Cancer Research Centre, Sheffield, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Academic Unit of Clinical Oncology, Sheffield Cancer Research Centre, Sheffield</wicri:regionArea></affiliation></author><author><name sortKey="Klotz, L" sort="Klotz, L" uniqKey="Klotz L" first="L" last="Klotz">L. Klotz</name><affiliation wicri:level="1"><nlm:affiliation>Division of Urology, Sunnybrook and Women's College Health Sciences Centre, Toronto, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Urology, Sunnybrook and Women's College Health Sciences Centre, Toronto</wicri:regionArea></affiliation></author><author><name sortKey="Pittman, K" sort="Pittman, K" uniqKey="Pittman K" first="K" last="Pittman">K. Pittman</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Oncology, The Queen Elizabeth Hospital, Woodville, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Oncology, The Queen Elizabeth Hospital, Woodville</wicri:regionArea></affiliation></author><author><name sortKey="Milecki, P" sort="Milecki, P" uniqKey="Milecki P" first="P" last="Milecki">P. Milecki</name><affiliation wicri:level="1"><nlm:affiliation>Department of Electroradiology, Poznan University of Medical Sciences, Poznan Department of Radiotherapy, Wielkopolskie Centrum Onkologii, Poznan, Poland.</nlm:affiliation><country xml:lang="fr">Pologne</country><wicri:regionArea>Department of Electroradiology, Poznan University of Medical Sciences, Poznan Department of Radiotherapy, Wielkopolskie Centrum Onkologii, Poznan</wicri:regionArea></affiliation></author><author><name sortKey="Ng, S" sort="Ng, S" uniqKey="Ng S" first="S" last="Ng">S. Ng</name><affiliation wicri:level="1"><nlm:affiliation>St John of God Hospital, Subiaco, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>St John of God Hospital, Subiaco</wicri:regionArea></affiliation></author><author><name sortKey="Chi, K N" sort="Chi, K N" uniqKey="Chi K" first="K N" last="Chi">K N Chi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Oncology, BC Cancer Agency, Vancouver, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medical Oncology, BC Cancer Agency, Vancouver</wicri:regionArea></affiliation></author><author><name sortKey="Balakumaran, A" sort="Balakumaran, A" uniqKey="Balakumaran A" first="A" last="Balakumaran">A. Balakumaran</name><affiliation><nlm:affiliation>Department of Hematology/Oncology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Hematology/Oncology.</wicri:noCountry></affiliation></author><author><name sortKey="Wei, R" sort="Wei, R" uniqKey="Wei R" first="R" last="Wei">R. Wei</name><affiliation wicri:level="1"><nlm:affiliation>Global Biostatistical Science, Amgen Inc., Thousand Oaks, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Global Biostatistical Science, Amgen Inc., Thousand Oaks</wicri:regionArea></affiliation></author><author><name sortKey="Wang, H" sort="Wang, H" uniqKey="Wang H" first="H" last="Wang">H. Wang</name><affiliation wicri:level="1"><nlm:affiliation>Global Biostatistical Science, Amgen Inc., Thousand Oaks, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Global Biostatistical Science, Amgen Inc., Thousand Oaks</wicri:regionArea></affiliation></author><author><name sortKey="Braun, A" sort="Braun, A" uniqKey="Braun A" first="A" last="Braun">A. Braun</name><affiliation><nlm:affiliation>Department of Hematology/Oncology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Hematology/Oncology.</wicri:noCountry></affiliation></author><author><name sortKey="Fizazi, K" sort="Fizazi, K" uniqKey="Fizazi K" first="K" last="Fizazi">K. Fizazi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Oncology, Institut Gustave Roussy, University of Paris Sud, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Oncology, Institut Gustave Roussy, University of Paris Sud, Paris</wicri:regionArea></affiliation></author></analytic><series><title level="j">Annals of oncology : official journal of the European Society for Medical Oncology</title><idno type="eISSN">1569-8041</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Bone Density Conservation Agents (therapeutic use)</term><term>Bone Neoplasms (complications)</term><term>Bone Neoplasms (secondary)</term><term>Denosumab (therapeutic use)</term><term>Double-Blind Method</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Prostatic Neoplasms, Castration-Resistant (pathology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Agents de maintien de la densité osseuse (usage thérapeutique)</term><term>Dénosumab (usage thérapeutique)</term><term>Humains</term><term>Mâle</term><term>Méthode en double aveugle</term><term>Sujet âgé</term><term>Tumeurs osseuses ()</term><term>Tumeurs osseuses (secondaire)</term><term>Tumeurs prostatiques résistantes à la castration (anatomopathologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Bone Density Conservation Agents</term><term>Denosumab</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Tumeurs prostatiques résistantes à la castration</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Bone Neoplasms</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Prostatic Neoplasms, Castration-Resistant</term></keywords><keywords scheme="MESH" qualifier="secondaire" xml:lang="fr"><term>Tumeurs osseuses</term></keywords><keywords scheme="MESH" qualifier="secondary" xml:lang="en"><term>Bone Neoplasms</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Agents de maintien de la densité osseuse</term><term>Dénosumab</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Double-Blind Method</term><term>Humans</term><term>Male</term><term>Middle Aged</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Humains</term><term>Mâle</term><term>Méthode en double aveugle</term><term>Sujet âgé</term><term>Tumeurs osseuses</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In a phase III trial in patients with castration-resistant prostate cancer (CRPC) and bone metastases, denosumab was superior to zoledronic acid in reducing skeletal-related events (SREs; radiation to bone, pathologic fracture, surgery to bone, or spinal cord compression). This study reassessed the efficacy of denosumab using symptomatic skeletal events (SSEs) as a prespecified exploratory end point.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25425475</PMID><DateCreated><Year>2015</Year><Month>01</Month><Day>24</Day></DateCreated><DateCompleted><Year>2016</Year><Month>02</Month><Day>24</Day></DateCompleted><DateRevised><Year>2016</Year><Month>12</Month><Day>15</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1569-8041</ISSN><JournalIssue CitedMedium="Internet"><Volume>26</Volume><Issue>2</Issue><PubDate><Year>2015</Year><Month>Feb</Month></PubDate></JournalIssue><Title>Annals of oncology : official journal of the European Society for Medical Oncology</Title><ISOAbbreviation>Ann. Oncol.</ISOAbbreviation></Journal><ArticleTitle>Denosumab for the prevention of skeletal complications in metastatic castration-resistant prostate cancer: comparison of skeletal-related events and symptomatic skeletal events.</ArticleTitle><Pagination><MedlinePgn>368-74</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1093/annonc/mdu519</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">In a phase III trial in patients with castration-resistant prostate cancer (CRPC) and bone metastases, denosumab was superior to zoledronic acid in reducing skeletal-related events (SREs; radiation to bone, pathologic fracture, surgery to bone, or spinal cord compression). This study reassessed the efficacy of denosumab using symptomatic skeletal events (SSEs) as a prespecified exploratory end point.</AbstractText><AbstractText Label="PATIENTS AND METHODS" NlmCategory="METHODS">Patients with CRPC, no previous bisphosphonate exposure, and radiographic evidence of bone metastasis were randomized to subcutaneous denosumab 120 mg plus i.v. placebo every 4 weeks (Q4W), or i.v. zoledronic acid 4 mg plus subcutaneous placebo Q4W during the blinded treatment phase. SSEs were defined as radiation to bone, symptomatic pathologic fracture, surgery to bone, or symptomatic spinal cord compression. The relationship between SSE or SRE and time to moderate/severe pain was assessed using the Brief Pain Inventory Short Form.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Treatment with denosumab significantly reduced the risk of developing first SSE [HR, 0.78; 95% confidence interval (CI) 0.66-0.93; P = 0.005] and first and subsequent SSEs (rate ratio, 0.78; 95% CI 0.65-0.92; P = 0.004) compared with zoledronic acid. The treatment differences in the number of patients with SSEs or SREs were similar (n = 48 and n = 45, respectively). Among patients with no/mild pain at baseline, both SSEs and SREs were associated with moderate/severe pain development (P < 0.0001). Fewer patients had skeletal complications, particularly fractures, when defined as SSE versus SRE.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">In patients with CRPC and bone metastases, denosumab reduced the risk of skeletal complications versus zoledronic acid regardless of whether the end point was defined as SSE or SRE.</AbstractText><CopyrightInformation>© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Smith</LastName><ForeName>M R</ForeName><Initials>MR</Initials><AffiliationInfo><Affiliation>Department of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Boston, USA smith.matthew@mgh.harvard.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Coleman</LastName><ForeName>R E</ForeName><Initials>RE</Initials><AffiliationInfo><Affiliation>Academic Unit of Clinical Oncology, Sheffield Cancer Research Centre, Sheffield, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Klotz</LastName><ForeName>L</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Division of Urology, Sunnybrook and Women's College Health Sciences Centre, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pittman</LastName><ForeName>K</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Medical Oncology, The Queen Elizabeth Hospital, Woodville, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Milecki</LastName><ForeName>P</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Electroradiology, Poznan University of Medical Sciences, Poznan Department of Radiotherapy, Wielkopolskie Centrum Onkologii, Poznan, Poland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ng</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>St John of God Hospital, Subiaco, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chi</LastName><ForeName>K N</ForeName><Initials>KN</Initials><AffiliationInfo><Affiliation>Department of Medical Oncology, BC Cancer Agency, Vancouver, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Balakumaran</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Hematology/Oncology.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wei</LastName><ForeName>R</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Global Biostatistical Science, Amgen Inc., Thousand Oaks, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>H</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Global Biostatistical Science, Amgen Inc., Thousand Oaks, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Braun</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Hematology/Oncology.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fizazi</LastName><ForeName>K</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Medical Oncology, Institut Gustave Roussy, University of Paris Sud, Paris, France.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>K24 CA121990</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D017428">Clinical Trial, Phase III</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016449">Randomized Controlled Trial</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>11</Month><Day>25</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Ann Oncol</MedlineTA><NlmUniqueID>9007735</NlmUniqueID><ISSNLinking>0923-7534</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D050071">Bone Density Conservation Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>4EQZ6YO2HI</RegistryNumber><NameOfSubstance UI="D000069448">Denosumab</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>N Engl J Med. 2013 Jul 18;369(3):213-23</RefSource><PMID Version="1">23863050</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Clin Cancer Res. 2006 Oct 15;12(20 Pt 2):6243s-6249s</RefSource><PMID Version="1">17062708</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Hum Pathol. 2000 May;31(5):578-83</RefSource><PMID Version="1">10836297</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Natl Cancer Inst. 2002 Oct 2;94(19):1458-68</RefSource><PMID Version="1">12359855</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Lancet. 2011 Mar 5;377(9768):813-22</RefSource><PMID 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UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001859" MajorTopicYN="N">Bone Neoplasms</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000556" MajorTopicYN="Y">secondary</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000069448" MajorTopicYN="N">Denosumab</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004311" MajorTopicYN="N">Double-Blind Method</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D064129" MajorTopicYN="N">Prostatic Neoplasms, Castration-Resistant</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading></MeshHeadingList><OtherID Source="NLM">PMC4304378</OtherID><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">denosumab</Keyword><Keyword MajorTopicYN="N">phase III</Keyword><Keyword MajorTopicYN="N">prostate cancer</Keyword><Keyword MajorTopicYN="N">skeletal-related events</Keyword><Keyword MajorTopicYN="N">symptomatic skeletal events</Keyword><Keyword MajorTopicYN="N">zoledronic acid</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2014</Year><Month>11</Month><Day>27</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2014</Year><Month>11</Month><Day>27</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>2</Month><Day>26</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">25425475</ArticleId><ArticleId IdType="pii">mdu519</ArticleId><ArticleId IdType="doi">10.1093/annonc/mdu519</ArticleId><ArticleId IdType="pmc">PMC4304378</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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