An exploratory phase 2 study of investigational Aurora A kinase inhibitor alisertib (MLN8237) in acute myelogenous leukemia and myelodysplastic syndromes
Identifieur interne : 000282 ( France/Analysis ); précédent : 000281; suivant : 000283An exploratory phase 2 study of investigational Aurora A kinase inhibitor alisertib (MLN8237) in acute myelogenous leukemia and myelodysplastic syndromes
Auteurs : Stuart L. Goldberg [États-Unis] ; Pierre Fenaux [France] ; Michael D. Craig [États-Unis] ; Emmanuel Gyan [France] ; John Lister [États-Unis] ; Jeannine Kassis [Canada] ; Arnaud Pigneux [France] ; Gary J. Schiller [États-Unis] ; Jungah Jung [États-Unis] ; E. Jane Leonard [États-Unis] ; Howard Fingert [États-Unis] ; Peter Westervelt [États-Unis]Source :
- Leukemia Research Reports [ 2213-0489 ] ; 2014.
Abstract
Alisertib (MLN8237) is an investigational, oral, selective, Aurora A kinase (AAK) inhibitor. In this phase 2 trial, 57 patients with acute myeloid leukemia (AML) or high-grade myelodysplastic syndrome received alisertib 50 mg BID for 7 days in 21-day cycles. Responses in 6/35 AML patients (17% response rate with an additional 49% stable disease, 34% transfusion independence) included 1 complete response lasting >1 year. No responses were observed in MDS patients. Adverse events >30% included diarrhea, fatigue, nausea, febrile neutropenia, and stomatitis. Results suggest modest activity in AML, supporting further research to better understand how AAK inhibition may induce leukemic cell senescence.
Url:
DOI: 10.1016/j.lrr.2014.06.003
PubMed: 25068104
PubMed Central: 4110881
Affiliations:
- Canada, France, États-Unis
- Californie, Massachusetts, Missouri (État), New Jersey, Pennsylvanie, Virginie-Occidentale, Île-de-France
- Bobigny
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PMC:4110881Le document en format XML
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Jane Leonard</name><affiliation wicri:level="2"><nlm:aff id="aff0045">Takeda Pharmaceuticals International Co., Cambridge, MA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Takeda Pharmaceuticals International Co., Cambridge, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Fingert, Howard" sort="Fingert, Howard" uniqKey="Fingert H" first="Howard" last="Fingert">Howard Fingert</name><affiliation wicri:level="2"><nlm:aff id="aff0045">Takeda Pharmaceuticals International Co., Cambridge, MA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Takeda Pharmaceuticals International Co., Cambridge, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Westervelt, Peter" sort="Westervelt, Peter" uniqKey="Westervelt P" first="Peter" last="Westervelt">Peter Westervelt</name><affiliation wicri:level="2"><nlm:aff id="aff0050">Division of Oncology, Washington University Medical School, St. Louis, MO, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Oncology, Washington University Medical School, St. Louis, MO</wicri:regionArea><placeName><region type="state">Missouri (État)</region></placeName></affiliation></author></analytic><series><title level="j">Leukemia Research Reports</title><idno type="eISSN">2213-0489</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Alisertib (MLN8237) is an investigational, oral, selective, Aurora A kinase (AAK) inhibitor. In this phase 2 trial, 57 patients with acute myeloid leukemia (AML) or high-grade myelodysplastic syndrome received alisertib 50 mg BID for 7 days in 21-day cycles. Responses in 6/35 AML patients (17% response rate with an additional 49% stable disease, 34% transfusion independence) included 1 complete response lasting >1 year. No responses were observed in MDS patients. Adverse events >30% included diarrhea, fatigue, nausea, febrile neutropenia, and stomatitis. Results suggest modest activity in AML, supporting further research to better understand how AAK inhibition may induce leukemic cell senescence.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Manfredi, M G" uniqKey="Manfredi M">M.G. Manfredi</name></author><author><name sortKey="Ecsedy, J A" uniqKey="Ecsedy J">J.A. Ecsedy</name></author><author><name sortKey="Meetze, K A" uniqKey="Meetze K">K.A. 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Schellens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dar, Aa" uniqKey="Dar A">AA Dar</name></author><author><name sortKey="Goff, Lw" uniqKey="Goff L">LW Goff</name></author><author><name sortKey="Majid, S" uniqKey="Majid S">S Majid</name></author><author><name sortKey="Berlin, J" uniqKey="Berlin J">J Berlin</name></author><author><name sortKey="El Rifai, W" uniqKey="El Rifai W">W. El-Rifai</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Canada</li><li>France</li><li>États-Unis</li></country><region><li>Californie</li><li>Massachusetts</li><li>Missouri (État)</li><li>New Jersey</li><li>Pennsylvanie</li><li>Virginie-Occidentale</li><li>Île-de-France</li></region><settlement><li>Bobigny</li></settlement></list><tree><country name="États-Unis"><region name="New Jersey"><name sortKey="Goldberg, Stuart L" sort="Goldberg, Stuart L" uniqKey="Goldberg S" first="Stuart L." last="Goldberg">Stuart L. Goldberg</name></region><name sortKey="Craig, Michael D" sort="Craig, Michael D" uniqKey="Craig M" first="Michael D." last="Craig">Michael D. Craig</name><name sortKey="Fingert, Howard" sort="Fingert, Howard" uniqKey="Fingert H" first="Howard" last="Fingert">Howard Fingert</name><name sortKey="Jane Leonard, E" sort="Jane Leonard, E" uniqKey="Jane Leonard E" first="E." last="Jane Leonard">E. Jane Leonard</name><name sortKey="Jung, Jungah" sort="Jung, Jungah" uniqKey="Jung J" first="Jungah" last="Jung">Jungah Jung</name><name sortKey="Lister, John" sort="Lister, John" uniqKey="Lister J" first="John" last="Lister">John Lister</name><name sortKey="Schiller, Gary J" sort="Schiller, Gary J" uniqKey="Schiller G" first="Gary J." last="Schiller">Gary J. Schiller</name><name sortKey="Westervelt, Peter" sort="Westervelt, Peter" uniqKey="Westervelt P" first="Peter" last="Westervelt">Peter Westervelt</name></country><country name="France"><region name="Île-de-France"><name sortKey="Fenaux, Pierre" sort="Fenaux, Pierre" uniqKey="Fenaux P" first="Pierre" last="Fenaux">Pierre Fenaux</name></region><name sortKey="Gyan, Emmanuel" sort="Gyan, Emmanuel" uniqKey="Gyan E" first="Emmanuel" last="Gyan">Emmanuel Gyan</name><name sortKey="Pigneux, Arnaud" sort="Pigneux, Arnaud" uniqKey="Pigneux A" first="Arnaud" last="Pigneux">Arnaud Pigneux</name></country><country name="Canada"><noRegion><name sortKey="Kassis, Jeannine" sort="Kassis, Jeannine" uniqKey="Kassis J" first="Jeannine" last="Kassis">Jeannine Kassis</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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