AustralieFrV1, Main, Exploration, bibRecord, 009653

Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Commentary

Identifieur interne : 009653 ( Main/Exploration ); précédent : 009652; suivant : 009654

Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Commentary

Auteurs : John Goldman [Royaume-Uni] ; Jorge Cortes [États-Unis] ; Philippe Rousselot [France] ; Dong-Wook Kim [Corée du Sud] ; Ellen Ritchie [États-Unis] ; Nelson Hamerschlak [Brésil] ; Steven Coutre [États-Unis] ; Andreas Hochhaus [Allemagne] ; Francois Guilhot [France] ; Giuseppe Saglio [Italie] ; Jane Apperley [Royaume-Uni] ; Oliver Ottmann [Allemagne] ; Neil Shah [États-Unis] ; Philipp Erben [Allemagne] ; Susan Branford [Australie] ; Prasheen Agarwal [États-Unis] ; Ashwin Gollerkeri [États-Unis] ; Michele Baccarani [Italie]

Source :

Blood [ 0006-4971 ] ; 2007.

RBID : Pascal:07-0282704

Descripteurs français

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

English descriptors

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

Abstract

The prognosis for patients with chronic myeloid leukemia (CML) in myeloid blast crisis (MBC) or lymphoid blast crisis (LBC) remains poor. Although imatinib can induce responses in a subset of these patients, resistance to the drug develops rapidly. Dasatinib is a novel, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases. After promising phase 1 results, we report the results of phase 2 clinical trials of dasatinib in patients with imatinib-resistant or -intolerant blast crisis CML (MBC, n = 74; LBC, n = 42). At the 8-month follow-up, dasatinib induced major hematologic responses (MaHRs) in 34% and 31% of MBC- and LBC-CML patients and major cytogenetic responses (MCyRs) in 31% and 50% of these patients, respectively. Most (86%) of these MCyRs were complete cytogenetic responses (CCyRs). Responses were rapid and durable: 88% and 46%, respectively, of MBC- and LBC-CML patients achieving MaHR had not experienced disease progression at the 8-month follow-up. Response rates were similar in patients with and without BCR-ABL mutations known to confer resistance to imatinib. Dasatinib was well tolerated. Nonhematologic adverse events were mild to moderate. Cytopenias were common and could be managed by dose modification. Dasatinib is highly active and produces hematologic and cytogenetic responses in a significant number of patients with imatinib-resistant or -intolerant MBC- and LBC-CML. These trials were registered at www.clinicaltrials.gov as #CA180006 and #CA180015.

Affiliations:

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Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Commentary</title>
<author><name sortKey="Goldman, John" sort="Goldman, John" uniqKey="Goldman J" first="John" last="Goldman">John Goldman</name>
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<author><name sortKey="Cortes, Jorge" sort="Cortes, Jorge" uniqKey="Cortes J" first="Jorge" last="Cortes">Jorge Cortes</name>
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<author><name sortKey="Coutre, Steven" sort="Coutre, Steven" uniqKey="Coutre S" first="Steven" last="Coutre">Steven Coutre</name>
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<author><name sortKey="Apperley, Jane" sort="Apperley, Jane" uniqKey="Apperley J" first="Jane" last="Apperley">Jane Apperley</name>
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<author><name sortKey="Ottmann, Oliver" sort="Ottmann, Oliver" uniqKey="Ottmann O" first="Oliver" last="Ottmann">Oliver Ottmann</name>
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<wicri:noRegion>Frankfurt-am-Main</wicri:noRegion>
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<wicri:noRegion>Johann Wolfgang Goethe Universität</wicri:noRegion>
</affiliation>
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<author><name sortKey="Shah, Neil" sort="Shah, Neil" uniqKey="Shah N" first="Neil" last="Shah">Neil Shah</name>
<affiliation wicri:level="1"><inist:fA14 i1="13"><s1>University College of Los Angeles</s1>
<s2>CA</s2>
<s3>USA</s3>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>University College of Los Angeles</wicri:noRegion>
</affiliation>
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<author><name sortKey="Erben, Philipp" sort="Erben, Philipp" uniqKey="Erben P" first="Philipp" last="Erben">Philipp Erben</name>
<affiliation wicri:level="3"><inist:fA14 i1="08"><s1>Medizinische Fakultät Mannheim, Universität Heidelberg</s1>
<s2>Mannheim</s2>
<s3>DEU</s3>
<sZ>8 aut.</sZ>
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</inist:fA14>
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<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="Branford, Susan" sort="Branford, Susan" uniqKey="Branford S" first="Susan" last="Branford">Susan Branford</name>
<affiliation wicri:level="1"><inist:fA14 i1="14"><s1>Division of Hematology, Institute of Medical and Veterinary Science</s1>
<s2>Adelaide</s2>
<s3>AUS</s3>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Adelaide</wicri:noRegion>
</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="15"><s1>Bristol-Myers Squibb</s1>
<s2>Wallingford, CT</s2>
<s3>USA</s3>
<sZ>16 aut.</sZ>
<sZ>17 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="15"><s1>Bristol-Myers Squibb</s1>
<s2>Wallingford, CT</s2>
<s3>USA</s3>
<sZ>16 aut.</sZ>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Bristol-Myers Squibb</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Baccarani, Michele" sort="Baccarani, Michele" uniqKey="Baccarani M" first="Michele" last="Baccarani">Michele Baccarani</name>
<affiliation wicri:level="1"><inist:fA14 i1="16"><s1>Istituto di Ematologica E Oncologica Medica, Policlinico S. Orsola</s1>
<s2>Bologna</s2>
<s3>ITA</s3>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>Italie</country>
<wicri:noRegion>Bologna</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>Blast transformation</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>Transformation blastique</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">The prognosis for patients with chronic myeloid leukemia (CML) in myeloid blast crisis (MBC) or lymphoid blast crisis (LBC) remains poor. Although imatinib can induce responses in a subset of these patients, resistance to the drug develops rapidly. Dasatinib is a novel, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases. After promising phase 1 results, we report the results of phase 2 clinical trials of dasatinib in patients with imatinib-resistant or -intolerant blast crisis CML (MBC, n = 74; LBC, n = 42). At the 8-month follow-up, dasatinib induced major hematologic responses (MaHRs) in 34% and 31% of MBC- and LBC-CML patients and major cytogenetic responses (MCyRs) in 31% and 50% of these patients, respectively. Most (86%) of these MCyRs were complete cytogenetic responses (CCyRs). Responses were rapid and durable: 88% and 46%, respectively, of MBC- and LBC-CML patients achieving MaHR had not experienced disease progression at the 8-month follow-up. Response rates were similar in patients with and without BCR-ABL mutations known to confer resistance to imatinib. Dasatinib was well tolerated. Nonhematologic adverse events were mild to moderate. Cytopenias were common and could be managed by dose modification. Dasatinib is highly active and produces hematologic and cytogenetic responses in a significant number of patients with imatinib-resistant or -intolerant MBC- and LBC-CML. These trials were registered at www.clinicaltrials.gov as #CA180006 and #CA180015.</div>
</front>
</TEI>
<affiliations><list><country><li>Allemagne</li>
<li>Australie</li>
<li>Brésil</li>
<li>Corée du Sud</li>
<li>France</li>
<li>Italie</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region><li>Angleterre</li>
<li>Bade-Wurtemberg</li>
<li>District de Karlsruhe</li>
<li>Grand Londres</li>
<li>Nouvelle-Aquitaine</li>
<li>Poitou-Charentes</li>
<li>État de São Paulo</li>
<li>Île-de-France</li>
</region>
<settlement><li>Londres</li>
<li>Mannheim</li>
<li>Paris</li>
<li>Poitiers</li>
<li>São Paulo</li>
</settlement>
</list>
<tree><country name="Royaume-Uni"><noRegion><name sortKey="Goldman, John" sort="Goldman, John" uniqKey="Goldman J" first="John" last="Goldman">John Goldman</name>
</noRegion>
<name sortKey="Apperley, Jane" sort="Apperley, Jane" uniqKey="Apperley J" first="Jane" last="Apperley">Jane Apperley</name>
</country>
<country name="États-Unis"><noRegion><name sortKey="Cortes, Jorge" sort="Cortes, Jorge" uniqKey="Cortes J" first="Jorge" last="Cortes">Jorge Cortes</name>
</noRegion>
<name sortKey="Agarwal, Prasheen" sort="Agarwal, Prasheen" uniqKey="Agarwal P" first="Prasheen" last="Agarwal">Prasheen Agarwal</name>
<name sortKey="Coutre, Steven" sort="Coutre, Steven" uniqKey="Coutre S" first="Steven" last="Coutre">Steven Coutre</name>
<name sortKey="Gollerkeri, Ashwin" sort="Gollerkeri, Ashwin" uniqKey="Gollerkeri A" first="Ashwin" last="Gollerkeri">Ashwin Gollerkeri</name>
<name sortKey="Ritchie, Ellen" sort="Ritchie, Ellen" uniqKey="Ritchie E" first="Ellen" last="Ritchie">Ellen Ritchie</name>
<name sortKey="Shah, Neil" sort="Shah, Neil" uniqKey="Shah N" first="Neil" last="Shah">Neil Shah</name>
</country>
<country name="France"><region name="Île-de-France"><name sortKey="Rousselot, Philippe" sort="Rousselot, Philippe" uniqKey="Rousselot P" first="Philippe" last="Rousselot">Philippe Rousselot</name>
</region>
<name sortKey="Guilhot, Francois" sort="Guilhot, Francois" uniqKey="Guilhot F" first="Francois" last="Guilhot">Francois Guilhot</name>
</country>
<country name="Corée du Sud"><noRegion><name sortKey="Kim, Dong Wook" sort="Kim, Dong Wook" uniqKey="Kim D" first="Dong-Wook" last="Kim">Dong-Wook Kim</name>
</noRegion>
</country>
<country name="Brésil"><region name="État de São Paulo"><name sortKey="Hamerschlak, Nelson" sort="Hamerschlak, Nelson" uniqKey="Hamerschlak N" first="Nelson" last="Hamerschlak">Nelson Hamerschlak</name>
</region>
</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="Erben, Philipp" sort="Erben, Philipp" uniqKey="Erben P" first="Philipp" last="Erben">Philipp Erben</name>
<name sortKey="Ottmann, Oliver" sort="Ottmann, Oliver" uniqKey="Ottmann O" first="Oliver" last="Ottmann">Oliver Ottmann</name>
</country>
<country name="Italie"><noRegion><name sortKey="Saglio, Giuseppe" sort="Saglio, Giuseppe" uniqKey="Saglio G" first="Giuseppe" last="Saglio">Giuseppe Saglio</name>
</noRegion>
<name sortKey="Baccarani, Michele" sort="Baccarani, Michele" uniqKey="Baccarani M" first="Michele" last="Baccarani">Michele Baccarani</name>
</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 complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Commentary

Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Commentary

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