AustralieFrV1, Main, Exploration, bibRecord, 009651

Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase. Commentary

Identifieur interne : 009651 ( Main/Exploration ); précédent : 009650; suivant : 009652

Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase. Commentary

Auteurs : Francois Guilhot [France] ; Jane Apperley [Royaume-Uni] ; Dong-Wook Kim [Corée du Sud] ; Eduardo O. Bullorsky [Argentine] ; Michele Baccarani [Italie] ; Gail J. Roboz [États-Unis] ; Sergio Amadori [Italie] ; Carmino A. De Souza [Brésil] ; Jeffrey H. Lipton [Canada] ; Andreas Hochhaus [Allemagne] ; Dominik Heim [Suisse] ; Richard A. Larson [États-Unis] ; Susan Branford [Australie] ; Martin C. Muller [Allemagne] ; Prasheen Agarwal [États-Unis] ; Ashwin Gollerkeri [États-Unis] ; Moshe Talpaz [États-Unis] ; Stephen O'Brien [États-Unis]

Source :

Blood [ 0006-4971 ] ; 2007.

RBID : Pascal:07-0373347

Descripteurs français

Pascal (Inist)
- Imatinib, Anticancéreux, Cytogénétique, Homme, Protein-tyrosine kinase, Inhibiteur enzyme, Résistance traitement, Hématologie, Dasatinib, Leucémie myéloïde chronique.
Wicri :
- topic : Homme.

English descriptors

KwdEn :
- Antineoplastic agent, Chronic myelocytic leukemia, Cytogenetics, Enzyme inhibitor, Hematology, Human, Imatinib, Protein-tyrosine kinase, Treatment resistance.

Abstract

Treatment options are limited for patients with imatinib-resistant or -intolerant accelerated phase chronic myeloid leukemia (CML-AP). Dasatinib is a novel, potent, oral, multitargeted kinase inhibitor of BCR-ABL and SRC-family kinases that showed marked efficacy in a phase 1 trial of patients with imatinib-resistant CML. Results are presented for 107 patients with CML-AP with imatinib-resistance or -intolerance from a phase 2, open-label study further evaluating dasatinib efficacy and safety. At 8 months' minimum follow-up, 81%, 64%, and 39% of patients achieved overall, major (MaHR), and complete hematologic responses, respectively, whereas 33% and 24% attained major and complete cytogenetic remission. Of 69 patients who achieved MaHR, 7 progressed. Seventy-six percent of patients are estimated to be alive and progression-free at 10 months. Response rates for the 60% of patients with baseline BCR-ABL mutations did not differ from the total population. Dasatinib was well tolerated: most nonhematologic adverse events (AEs) were mild to moderate; no imatinib-intolerant patients discontinued dasatinib because of AEs. Although common (76% of patients with severe neutropenia), cytopenias were manageable through dose modification. In summary, dasatinib induced significant hematologic and cytogenetic responses in patients with imatinib resistance or intolerance, was well tolerated, and may represent a potent new therapeutic option for CML-AP. Further follow-up is warranted. This trial was registered at www. clinicaltrials.gov as #CA180005.

Affiliations:

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

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Le document en format XML

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<author><name sortKey="Lipton, Jeffrey H" sort="Lipton, Jeffrey H" uniqKey="Lipton J" first="Jeffrey H." last="Lipton">Jeffrey H. Lipton</name>
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<author><name sortKey="Hochhaus, Andreas" sort="Hochhaus, Andreas" uniqKey="Hochhaus A" first="Andreas" last="Hochhaus">Andreas Hochhaus</name>
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<author><name sortKey="Branford, Susan" sort="Branford, Susan" uniqKey="Branford S" first="Susan" last="Branford">Susan Branford</name>
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<author><name sortKey="Agarwal, Prasheen" sort="Agarwal, Prasheen" uniqKey="Agarwal P" first="Prasheen" last="Agarwal">Prasheen Agarwal</name>
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<author><name sortKey="Talpaz, Moshe" sort="Talpaz, Moshe" uniqKey="Talpaz M" first="Moshe" last="Talpaz">Moshe Talpaz</name>
<affiliation wicri:level="1"><inist:fA14 i1="15"><s1>Department of Leukemia, M.D. Anderson Cancer Center</s1>
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</inist:fA14>
<country>États-Unis</country>
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<author><name sortKey="O Brien, Stephen" sort="O Brien, Stephen" uniqKey="O Brien S" first="Stephen" last="O'Brien">Stephen O'Brien</name>
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<s3>USA</s3>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase. Commentary</title>
<author><name sortKey="Guilhot, Francois" sort="Guilhot, Francois" uniqKey="Guilhot F" first="Francois" last="Guilhot">Francois Guilhot</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Clinical Research Centre, Centre Hospitalier et Universitaire (CHU) La Miletrie</s1>
<s2>Poitiers</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Nouvelle-Aquitaine</region>
<region type="old region">Poitou-Charentes</region>
<settlement type="city">Poitiers</settlement>
</placeName>
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<author><name sortKey="Apperley, Jane" sort="Apperley, Jane" uniqKey="Apperley J" first="Jane" last="Apperley">Jane Apperley</name>
<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Hammersmith Hospital</s1>
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<author><name sortKey="Kim, Dong Wook" sort="Kim, Dong Wook" uniqKey="Kim D" first="Dong-Wook" last="Kim">Dong-Wook Kim</name>
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</inist:fA14>
<country>Corée du Sud</country>
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<author><name sortKey="Bullorsky, Eduardo O" sort="Bullorsky, Eduardo O" uniqKey="Bullorsky E" first="Eduardo O." last="Bullorsky">Eduardo O. Bullorsky</name>
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<s2>Buenos Aires</s2>
<s3>ARG</s3>
<sZ>4 aut.</sZ>
</inist:fA14>
<country>Argentine</country>
<wicri:noRegion>Buenos Aires</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Baccarani, Michele" sort="Baccarani, Michele" uniqKey="Baccarani M" first="Michele" last="Baccarani">Michele Baccarani</name>
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</affiliation>
</author>
<author><name sortKey="Roboz, Gail J" sort="Roboz, Gail J" uniqKey="Roboz G" first="Gail J." last="Roboz">Gail J. Roboz</name>
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<s3>USA</s3>
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</inist:fA14>
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<wicri:noRegion>New York, NY</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Amadori, Sergio" sort="Amadori, Sergio" uniqKey="Amadori S" first="Sergio" last="Amadori">Sergio Amadori</name>
<affiliation wicri:level="3"><inist:fA14 i1="07"><s1>Ospedale S. Eugenio, Divisione di Ematologia</s1>
<s2>Roma</s2>
<s3>ITA</s3>
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<placeName><settlement type="city">Rome</settlement>
<region nuts="2">Latium</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="De Souza, Carmino A" sort="De Souza, Carmino A" uniqKey="De Souza C" first="Carmino A." last="De Souza">Carmino A. De Souza</name>
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<s2>Campinas</s2>
<s3>BRA</s3>
<sZ>8 aut.</sZ>
</inist:fA14>
<country>Brésil</country>
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</placeName>
<orgName type="university">Université d'État de Campinas</orgName>
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</author>
<author><name sortKey="Lipton, Jeffrey H" sort="Lipton, Jeffrey H" uniqKey="Lipton J" first="Jeffrey H." last="Lipton">Jeffrey H. Lipton</name>
<affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Princess Margaret Hospital</s1>
<s2>Toronto, ON</s2>
<s3>CAN</s3>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>Princess Margaret Hospital</wicri:noRegion>
</affiliation>
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<author><name sortKey="Hochhaus, Andreas" sort="Hochhaus, Andreas" uniqKey="Hochhaus A" first="Andreas" last="Hochhaus">Andreas Hochhaus</name>
<affiliation wicri:level="3"><inist:fA14 i1="10"><s1>Medizinische Fakultät Mannheim, Universität Heidelberg</s1>
<s2>Mannheim</s2>
<s3>DEU</s3>
<sZ>10 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Mannheim</settlement>
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<author><name sortKey="Heim, Dominik" sort="Heim, Dominik" uniqKey="Heim D" first="Dominik" last="Heim">Dominik Heim</name>
<affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Department of Hematology, University Hospital</s1>
<s2>Basel</s2>
<s3>CHE</s3>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>Suisse</country>
<wicri:noRegion>Basel</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Larson, Richard A" sort="Larson, Richard A" uniqKey="Larson R" first="Richard A." last="Larson">Richard A. Larson</name>
<affiliation wicri:level="1"><inist:fA14 i1="12"><s1>University of Chicago</s1>
<s2>Chicago, IL</s2>
<s3>USA</s3>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>University of Chicago</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Branford, Susan" sort="Branford, Susan" uniqKey="Branford S" first="Susan" last="Branford">Susan Branford</name>
<affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Division of Hematology, Institute of Medical and Veterinary Science</s1>
<s2>Adelaide</s2>
<s3>AUS</s3>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Adelaide</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Muller, Martin C" sort="Muller, Martin C" uniqKey="Muller M" first="Martin C." last="Muller">Martin C. Muller</name>
<affiliation wicri:level="3"><inist:fA14 i1="10"><s1>Medizinische Fakultät Mannheim, Universität Heidelberg</s1>
<s2>Mannheim</s2>
<s3>DEU</s3>
<sZ>10 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Mannheim</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Agarwal, Prasheen" sort="Agarwal, Prasheen" uniqKey="Agarwal P" first="Prasheen" last="Agarwal">Prasheen Agarwal</name>
<affiliation wicri:level="1"><inist:fA14 i1="14"><s1>Bristol-Myers Squibb</s1>
<s2>Wallingford, CT</s2>
<s3>USA</s3>
<sZ>15 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Bristol-Myers Squibb</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gollerkeri, Ashwin" sort="Gollerkeri, Ashwin" uniqKey="Gollerkeri A" first="Ashwin" last="Gollerkeri">Ashwin Gollerkeri</name>
<affiliation wicri:level="1"><inist:fA14 i1="14"><s1>Bristol-Myers Squibb</s1>
<s2>Wallingford, CT</s2>
<s3>USA</s3>
<sZ>15 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Bristol-Myers Squibb</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Talpaz, Moshe" sort="Talpaz, Moshe" uniqKey="Talpaz M" first="Moshe" last="Talpaz">Moshe Talpaz</name>
<affiliation wicri:level="1"><inist:fA14 i1="15"><s1>Department of Leukemia, M.D. Anderson Cancer Center</s1>
<s2>Houston, TX</s2>
<s3>USA</s3>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Houston, TX</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="O Brien, Stephen" sort="O Brien, Stephen" uniqKey="O Brien S" first="Stephen" last="O'Brien">Stephen O'Brien</name>
<affiliation wicri:level="1"><inist:fA14 i1="16"><s1>Newcastle University</s1>
<s3>USA</s3>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Newcastle University</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Blood</title>
<title level="j" type="abbreviated">Blood</title>
<idno type="ISSN">0006-4971</idno>
<imprint><date when="2007">2007</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Blood</title>
<title level="j" type="abbreviated">Blood</title>
<idno type="ISSN">0006-4971</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antineoplastic agent</term>
<term>Chronic myelocytic leukemia</term>
<term>Cytogenetics</term>
<term>Enzyme inhibitor</term>
<term>Hematology</term>
<term>Human</term>
<term>Imatinib</term>
<term>Protein-tyrosine kinase</term>
<term>Treatment resistance</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Imatinib</term>
<term>Anticancéreux</term>
<term>Cytogénétique</term>
<term>Homme</term>
<term>Protein-tyrosine kinase</term>
<term>Inhibiteur enzyme</term>
<term>Résistance traitement</term>
<term>Hématologie</term>
<term>Dasatinib</term>
<term>Leucémie myéloïde chronique</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Treatment options are limited for patients with imatinib-resistant or -intolerant accelerated phase chronic myeloid leukemia (CML-AP). Dasatinib is a novel, potent, oral, multitargeted kinase inhibitor of BCR-ABL and SRC-family kinases that showed marked efficacy in a phase 1 trial of patients with imatinib-resistant CML. Results are presented for 107 patients with CML-AP with imatinib-resistance or -intolerance from a phase 2, open-label study further evaluating dasatinib efficacy and safety. At 8 months' minimum follow-up, 81%, 64%, and 39% of patients achieved overall, major (MaHR), and complete hematologic responses, respectively, whereas 33% and 24% attained major and complete cytogenetic remission. Of 69 patients who achieved MaHR, 7 progressed. Seventy-six percent of patients are estimated to be alive and progression-free at 10 months. Response rates for the 60% of patients with baseline BCR-ABL mutations did not differ from the total population. Dasatinib was well tolerated: most nonhematologic adverse events (AEs) were mild to moderate; no imatinib-intolerant patients discontinued dasatinib because of AEs. Although common (76% of patients with severe neutropenia), cytopenias were manageable through dose modification. In summary, dasatinib induced significant hematologic and cytogenetic responses in patients with imatinib resistance or intolerance, was well tolerated, and may represent a potent new therapeutic option for CML-AP. Further follow-up is warranted. This trial was registered at www. clinicaltrials.gov as #CA180005.</div>
</front>
</TEI>
<affiliations><list><country><li>Allemagne</li>
<li>Argentine</li>
<li>Australie</li>
<li>Brésil</li>
<li>Canada</li>
<li>Corée du Sud</li>
<li>France</li>
<li>Italie</li>
<li>Royaume-Uni</li>
<li>Suisse</li>
<li>États-Unis</li>
</country>
<region><li>Angleterre</li>
<li>Bade-Wurtemberg</li>
<li>District de Karlsruhe</li>
<li>Grand Londres</li>
<li>Latium</li>
<li>Nouvelle-Aquitaine</li>
<li>Poitou-Charentes</li>
<li>Région capitale de Séoul</li>
<li>État de São Paulo</li>
</region>
<settlement><li>Campinas</li>
<li>Londres</li>
<li>Mannheim</li>
<li>Poitiers</li>
<li>Rome</li>
<li>Séoul</li>
</settlement>
<orgName><li>Université d'État de Campinas</li>
</orgName>
</list>
<tree><country name="France"><region name="Nouvelle-Aquitaine"><name sortKey="Guilhot, Francois" sort="Guilhot, Francois" uniqKey="Guilhot F" first="Francois" last="Guilhot">Francois Guilhot</name>
</region>
</country>
<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Apperley, Jane" sort="Apperley, Jane" uniqKey="Apperley J" first="Jane" last="Apperley">Jane Apperley</name>
</region>
</country>
<country name="Corée du Sud"><region name="Région capitale de Séoul"><name sortKey="Kim, Dong Wook" sort="Kim, Dong Wook" uniqKey="Kim D" first="Dong-Wook" last="Kim">Dong-Wook Kim</name>
</region>
</country>
<country name="Argentine"><noRegion><name sortKey="Bullorsky, Eduardo O" sort="Bullorsky, Eduardo O" uniqKey="Bullorsky E" first="Eduardo O." last="Bullorsky">Eduardo O. Bullorsky</name>
</noRegion>
</country>
<country name="Italie"><noRegion><name sortKey="Baccarani, Michele" sort="Baccarani, Michele" uniqKey="Baccarani M" first="Michele" last="Baccarani">Michele Baccarani</name>
</noRegion>
<name sortKey="Amadori, Sergio" sort="Amadori, Sergio" uniqKey="Amadori S" first="Sergio" last="Amadori">Sergio Amadori</name>
</country>
<country name="États-Unis"><noRegion><name sortKey="Roboz, Gail J" sort="Roboz, Gail J" uniqKey="Roboz G" first="Gail J." last="Roboz">Gail J. Roboz</name>
</noRegion>
<name sortKey="Agarwal, Prasheen" sort="Agarwal, Prasheen" uniqKey="Agarwal P" first="Prasheen" last="Agarwal">Prasheen Agarwal</name>
<name sortKey="Gollerkeri, Ashwin" sort="Gollerkeri, Ashwin" uniqKey="Gollerkeri A" first="Ashwin" last="Gollerkeri">Ashwin Gollerkeri</name>
<name sortKey="Larson, Richard A" sort="Larson, Richard A" uniqKey="Larson R" first="Richard A." last="Larson">Richard A. Larson</name>
<name sortKey="O Brien, Stephen" sort="O Brien, Stephen" uniqKey="O Brien S" first="Stephen" last="O'Brien">Stephen O'Brien</name>
<name sortKey="Talpaz, Moshe" sort="Talpaz, Moshe" uniqKey="Talpaz M" first="Moshe" last="Talpaz">Moshe Talpaz</name>
</country>
<country name="Brésil"><region name="État de São Paulo"><name sortKey="De Souza, Carmino A" sort="De Souza, Carmino A" uniqKey="De Souza C" first="Carmino A." last="De Souza">Carmino A. De Souza</name>
</region>
</country>
<country name="Canada"><noRegion><name sortKey="Lipton, Jeffrey H" sort="Lipton, Jeffrey H" uniqKey="Lipton J" first="Jeffrey H." last="Lipton">Jeffrey H. Lipton</name>
</noRegion>
</country>
<country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Hochhaus, Andreas" sort="Hochhaus, Andreas" uniqKey="Hochhaus A" first="Andreas" last="Hochhaus">Andreas Hochhaus</name>
</region>
<name sortKey="Muller, Martin C" sort="Muller, Martin C" uniqKey="Muller M" first="Martin C." last="Muller">Martin C. Muller</name>
</country>
<country name="Suisse"><noRegion><name sortKey="Heim, Dominik" sort="Heim, Dominik" uniqKey="Heim D" first="Dominik" last="Heim">Dominik Heim</name>
</noRegion>
</country>
<country name="Australie"><noRegion><name sortKey="Branford, Susan" sort="Branford, Susan" uniqKey="Branford S" first="Susan" last="Branford">Susan Branford</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase. Commentary

Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase. Commentary

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