Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Commentary
Identifieur interne : 009652 ( Main/Exploration ); précédent : 009651; suivant : 009653Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Commentary
Auteurs : Jacob M. Rowe [États-Unis] ; Andreas Hochhaus [Allemagne] ; Hagop M. Kantarjian [États-Unis] ; Michele Baccarani [Italie] ; Jeffrey H. Lipton [Canada] ; Jane F. Apperley [Royaume-Uni] ; Brian J. Druker [États-Unis] ; Thierry Facon [France] ; Stuart L. Goldberg [États-Unis] ; Francisco Cervantes [Espagne] ; Dietger Niederwieser [Allemagne] ; Richard T. Silver [États-Unis] ; Richard M. Stone [États-Unis] ; Timothy P. Hughes [Australie] ; Martin C. Muller [Allemagne] ; Rana Ezzeddine [États-Unis] ; Athena M. Countouriotis [États-Unis] ; Neil P. Shah [États-Unis]Source :
- Blood [ 0006-4971 ] ; 2007.
Descripteurs français
- Pascal (Inist)
English descriptors
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Abstract
Although imatinib induces marked responses in patients with chronic myeloid leukemia (CML), resistance is increasingly problematic, and treatment options for imatinib-resistant or -intolerant CML are limited. Dasatinib, a novel, highly potent, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, induced cytogenetic responses in a phase 1 study in imatinib-resistant or -intolerant CML and was well tolerated. Initial results are presented from a phase 2 study of 186 patients with imatinib-resistant or -intolerant chronic-phase CML (CML-CP) designed to further establish the efficacy and safety of dasatinib (70 mg twice daily). At 8-months' follow-up, dasatinib induced notable responses, with 90% and 52% of patients achieving complete hematologic and major cytogenetic responses (MCyR), respectively. Responses were long lasting: only 2% of patients achieving MCyR progressed or died. Importantly, comparable responses were achieved by patients carrying BCR-ABL mutations conferring imatinib resistance. Dasatinib also induced molecular responses, reducing BCR-ABL/ABL transcript ratios from 66% at baseline to 2.6% at 9 months. Nonhematologic adverse events were generally mild to moderate, and most cytopenias were effectively managed with dose modifications. Cross-intolerance with imatinib was not evident. To conclude, dasatinib induces notable responses in imatinib-resistant or -intolerant CML-CP, is well tolerated, and represents a promising therapeutic option for these patients. This trial was registered at www.clinicaltrials.gov as CA180013.
Affiliations:
- Allemagne, Australie, Canada, Espagne, France, Italie, Royaume-Uni, États-Unis
- Angleterre, Bade-Wurtemberg, Catalogne, District de Karlsruhe, Grand Londres, Hauts-de-France, Nord-Pas-de-Calais, Oregon
- Barcelone, Lille, Londres, Mannheim, Portland
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Commentary</title><author><name sortKey="Rowe, Jacob M" sort="Rowe, Jacob M" uniqKey="Rowe J" first="Jacob M." last="Rowe">Jacob M. Rowe</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>HEMATOLOGY, RAMBAM MEDICAL CENTER</s1><s3>USA</s3><sZ>1 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>HEMATOLOGY, RAMBAM MEDICAL CENTER</wicri:noRegion></affiliation></author><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="02"><s1>III. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg</s1><s2>Mannheim</s2><s3>DEU</s3><sZ>2 aut.</sZ><sZ>15 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="Kantarjian, Hagop M" sort="Kantarjian, Hagop M" uniqKey="Kantarjian H" first="Hagop M." last="Kantarjian">Hagop M. 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Lipton</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Princess Margaret Hospital</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Princess Margaret Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Apperley, Jane F" sort="Apperley, Jane F" uniqKey="Apperley J" first="Jane F." last="Apperley">Jane F. Apperley</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Department of Haematology, Hammersmith Hospital</s1><s2>London</s2><s3>GBR</s3><sZ>6 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Druker, Brian J" sort="Druker, Brian J" uniqKey="Druker B" first="Brian J." last="Druker">Brian J. Druker</name><affiliation wicri:level="3"><inist:fA14 i1="07"><s1>Division of Hematology and Medical Oncology, Oregon Health Science University</s1><s2>Portland</s2><s3>USA</s3><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Portland</settlement><region type="state">Oregon</region></placeName></affiliation></author><author><name sortKey="Facon, Thierry" sort="Facon, Thierry" uniqKey="Facon T" first="Thierry" last="Facon">Thierry Facon</name><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>Hópital Claude Huriez</s1><s2>Lille</s2><s3>FRA</s3><sZ>8 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Goldberg, Stuart L" sort="Goldberg, Stuart L" uniqKey="Goldberg S" first="Stuart L." last="Goldberg">Stuart L. Goldberg</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Cancer Center, Hackensack University Medical Center</s1><s2>NJ</s2><s3>USA</s3><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>NJ</wicri:noRegion></affiliation></author><author><name sortKey="Cervantes, Francisco" sort="Cervantes, Francisco" uniqKey="Cervantes F" first="Francisco" last="Cervantes">Francisco Cervantes</name><affiliation wicri:level="3"><inist:fA14 i1="10"><s1>Department of Hematology, Hospital Clinic</s1><s2>Barcelona</s2><s3>ESP</s3><sZ>10 aut.</sZ></inist:fA14><country>Espagne</country><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Niederwieser, Dietger" sort="Niederwieser, Dietger" uniqKey="Niederwieser D" first="Dietger" last="Niederwieser">Dietger Niederwieser</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Medizinische Klinik und Poliklinik II, Universitätsklinikum Leipzig</s1><s3>DEU</s3><sZ>11 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Universitätsklinikum Leipzig</wicri:noRegion><wicri:noRegion>Medizinische Klinik und Poliklinik II, Universitätsklinikum Leipzig</wicri:noRegion></affiliation></author><author><name sortKey="Silver, Richard T" sort="Silver, Richard T" uniqKey="Silver R" first="Richard T." last="Silver">Richard T. Silver</name><affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Weill Medical College of Cornell University, New York Presbyterian Hospital</s1><s2>New York, NY</s2><s3>USA</s3><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>New York, NY</wicri:noRegion></affiliation></author><author><name sortKey="Stone, Richard M" sort="Stone, Richard M" uniqKey="Stone R" first="Richard M." last="Stone">Richard M. Stone</name><affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Department of Adult Oncology, Dana-Farber Cancer Institute</s1><s2>Boston, MA</s2><s3>USA</s3><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Boston, MA</wicri:noRegion></affiliation></author><author><name sortKey="Hughes, Timothy P" sort="Hughes, Timothy P" uniqKey="Hughes T" first="Timothy P." last="Hughes">Timothy P. Hughes</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>14 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="02"><s1>III. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg</s1><s2>Mannheim</s2><s3>DEU</s3><sZ>2 aut.</sZ><sZ>15 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="Ezzeddine, Rana" sort="Ezzeddine, Rana" uniqKey="Ezzeddine R" first="Rana" last="Ezzeddine">Rana Ezzeddine</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="Countouriotis, Athena M" sort="Countouriotis, Athena M" uniqKey="Countouriotis A" first="Athena M." last="Countouriotis">Athena M. Countouriotis</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="Shah, Neil P" sort="Shah, Neil P" uniqKey="Shah N" first="Neil P." last="Shah">Neil P. Shah</name><affiliation wicri:level="1"><inist:fA14 i1="16"><s1>Division of Hematology and Oncology, University College of San Francisco School of Medicine</s1><s2>CA</s2><s3>USA</s3><sZ>18 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>CA</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">07-0247406</idno><date when="2007">2007</date><idno type="stanalyst">PASCAL 07-0247406 INIST</idno><idno type="RBID">Pascal:07-0247406</idno><idno type="wicri:Area/PascalFrancis/Corpus">003C35</idno><idno type="wicri:Area/PascalFrancis/Curation">002453</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">003979</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">003979</idno><idno type="wicri:doubleKey">0006-4971:2007:Rowe J:dasatinib:induces:notable</idno><idno type="wicri:Area/Main/Merge">00A091</idno><idno type="wicri:Area/Main/Curation">009652</idno><idno type="wicri:Area/Main/Exploration">009652</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Commentary</title><author><name sortKey="Rowe, Jacob M" sort="Rowe, Jacob M" uniqKey="Rowe J" first="Jacob M." last="Rowe">Jacob M. Rowe</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>HEMATOLOGY, RAMBAM MEDICAL CENTER</s1><s3>USA</s3><sZ>1 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>HEMATOLOGY, RAMBAM MEDICAL CENTER</wicri:noRegion></affiliation></author><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="02"><s1>III. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg</s1><s2>Mannheim</s2><s3>DEU</s3><sZ>2 aut.</sZ><sZ>15 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="Kantarjian, Hagop M" sort="Kantarjian, Hagop M" uniqKey="Kantarjian H" first="Hagop M." last="Kantarjian">Hagop M. Kantarjian</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Leukemia, M.D. Anderson Cancer Center</s1><s2>Houston, TX</s2><s3>USA</s3><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Houston, TX</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="04"><s1>Department of Hematology-Oncology "Seragnoli," S Orsola-Malpighi University Hospital, University of Bologna</s1><s3>ITA</s3><sZ>4 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Department of Hematology-Oncology "Seragnoli," S Orsola-Malpighi University Hospital, University of Bologna</wicri:noRegion></affiliation></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="05"><s1>Princess Margaret Hospital</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Princess Margaret Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Apperley, Jane F" sort="Apperley, Jane F" uniqKey="Apperley J" first="Jane F." last="Apperley">Jane F. Apperley</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Department of Haematology, Hammersmith Hospital</s1><s2>London</s2><s3>GBR</s3><sZ>6 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Druker, Brian J" sort="Druker, Brian J" uniqKey="Druker B" first="Brian J." last="Druker">Brian J. Druker</name><affiliation wicri:level="3"><inist:fA14 i1="07"><s1>Division of Hematology and Medical Oncology, Oregon Health Science University</s1><s2>Portland</s2><s3>USA</s3><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Portland</settlement><region type="state">Oregon</region></placeName></affiliation></author><author><name sortKey="Facon, Thierry" sort="Facon, Thierry" uniqKey="Facon T" first="Thierry" last="Facon">Thierry Facon</name><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>Hópital Claude Huriez</s1><s2>Lille</s2><s3>FRA</s3><sZ>8 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Goldberg, Stuart L" sort="Goldberg, Stuart L" uniqKey="Goldberg S" first="Stuart L." last="Goldberg">Stuart L. Goldberg</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Cancer Center, Hackensack University Medical Center</s1><s2>NJ</s2><s3>USA</s3><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>NJ</wicri:noRegion></affiliation></author><author><name sortKey="Cervantes, Francisco" sort="Cervantes, Francisco" uniqKey="Cervantes F" first="Francisco" last="Cervantes">Francisco Cervantes</name><affiliation wicri:level="3"><inist:fA14 i1="10"><s1>Department of Hematology, Hospital Clinic</s1><s2>Barcelona</s2><s3>ESP</s3><sZ>10 aut.</sZ></inist:fA14><country>Espagne</country><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Niederwieser, Dietger" sort="Niederwieser, Dietger" uniqKey="Niederwieser D" first="Dietger" last="Niederwieser">Dietger Niederwieser</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Medizinische Klinik und Poliklinik II, Universitätsklinikum Leipzig</s1><s3>DEU</s3><sZ>11 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Universitätsklinikum Leipzig</wicri:noRegion><wicri:noRegion>Medizinische Klinik und Poliklinik II, Universitätsklinikum Leipzig</wicri:noRegion></affiliation></author><author><name sortKey="Silver, Richard T" sort="Silver, Richard T" uniqKey="Silver R" first="Richard T." last="Silver">Richard T. Silver</name><affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Weill Medical College of Cornell University, New York Presbyterian Hospital</s1><s2>New York, NY</s2><s3>USA</s3><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>New York, NY</wicri:noRegion></affiliation></author><author><name sortKey="Stone, Richard M" sort="Stone, Richard M" uniqKey="Stone R" first="Richard M." last="Stone">Richard M. Stone</name><affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Department of Adult Oncology, Dana-Farber Cancer Institute</s1><s2>Boston, MA</s2><s3>USA</s3><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Boston, MA</wicri:noRegion></affiliation></author><author><name sortKey="Hughes, Timothy P" sort="Hughes, Timothy P" uniqKey="Hughes T" first="Timothy P." last="Hughes">Timothy P. Hughes</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>14 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="02"><s1>III. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg</s1><s2>Mannheim</s2><s3>DEU</s3><sZ>2 aut.</sZ><sZ>15 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="Ezzeddine, Rana" sort="Ezzeddine, Rana" uniqKey="Ezzeddine R" first="Rana" last="Ezzeddine">Rana Ezzeddine</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="Countouriotis, Athena M" sort="Countouriotis, Athena M" uniqKey="Countouriotis A" first="Athena M." last="Countouriotis">Athena M. Countouriotis</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="Shah, Neil P" sort="Shah, Neil P" uniqKey="Shah N" first="Neil P." last="Shah">Neil P. Shah</name><affiliation wicri:level="1"><inist:fA14 i1="16"><s1>Division of Hematology and Oncology, University College of San Francisco School of Medicine</s1><s2>CA</s2><s3>USA</s3><sZ>18 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>CA</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>Imatinib</term><term>Protein-tyrosine kinase</term><term>Treatment</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Imatinib</term><term>Anticancéreux</term><term>Cytogénétique</term><term>Protein-tyrosine kinase</term><term>Inhibiteur enzyme</term><term>Traitement</term><term>Dasatinib</term><term>Leucémie myéloïde chronique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Although imatinib induces marked responses in patients with chronic myeloid leukemia (CML), resistance is increasingly problematic, and treatment options for imatinib-resistant or -intolerant CML are limited. Dasatinib, a novel, highly potent, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, induced cytogenetic responses in a phase 1 study in imatinib-resistant or -intolerant CML and was well tolerated. Initial results are presented from a phase 2 study of 186 patients with imatinib-resistant or -intolerant chronic-phase CML (CML-CP) designed to further establish the efficacy and safety of dasatinib (70 mg twice daily). At 8-months' follow-up, dasatinib induced notable responses, with 90% and 52% of patients achieving complete hematologic and major cytogenetic responses (MCyR), respectively. Responses were long lasting: only 2% of patients achieving MCyR progressed or died. Importantly, comparable responses were achieved by patients carrying BCR-ABL mutations conferring imatinib resistance. Dasatinib also induced molecular responses, reducing BCR-ABL/ABL transcript ratios from 66% at baseline to 2.6% at 9 months. Nonhematologic adverse events were generally mild to moderate, and most cytopenias were effectively managed with dose modifications. Cross-intolerance with imatinib was not evident. To conclude, dasatinib induces notable responses in imatinib-resistant or -intolerant CML-CP, is well tolerated, and represents a promising therapeutic option for these patients. This trial was registered at www.clinicaltrials.gov as CA180013.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>Canada</li><li>Espagne</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>Catalogne</li><li>District de Karlsruhe</li><li>Grand Londres</li><li>Hauts-de-France</li><li>Nord-Pas-de-Calais</li><li>Oregon</li></region><settlement><li>Barcelone</li><li>Lille</li><li>Londres</li><li>Mannheim</li><li>Portland</li></settlement></list><tree><country name="États-Unis"><noRegion><name sortKey="Rowe, Jacob M" sort="Rowe, Jacob M" uniqKey="Rowe J" first="Jacob M." last="Rowe">Jacob M. Rowe</name></noRegion><name sortKey="Countouriotis, Athena M" sort="Countouriotis, Athena M" uniqKey="Countouriotis A" first="Athena M." last="Countouriotis">Athena M. Countouriotis</name><name sortKey="Druker, Brian J" sort="Druker, Brian J" uniqKey="Druker B" first="Brian J." last="Druker">Brian J. Druker</name><name sortKey="Ezzeddine, Rana" sort="Ezzeddine, Rana" uniqKey="Ezzeddine R" first="Rana" last="Ezzeddine">Rana Ezzeddine</name><name sortKey="Goldberg, Stuart L" sort="Goldberg, Stuart L" uniqKey="Goldberg S" first="Stuart L." last="Goldberg">Stuart L. Goldberg</name><name sortKey="Kantarjian, Hagop M" sort="Kantarjian, Hagop M" uniqKey="Kantarjian H" first="Hagop M." last="Kantarjian">Hagop M. Kantarjian</name><name sortKey="Shah, Neil P" sort="Shah, Neil P" uniqKey="Shah N" first="Neil P." last="Shah">Neil P. Shah</name><name sortKey="Silver, Richard T" sort="Silver, Richard T" uniqKey="Silver R" first="Richard T." last="Silver">Richard T. Silver</name><name sortKey="Stone, Richard M" sort="Stone, Richard M" uniqKey="Stone R" first="Richard M." last="Stone">Richard M. Stone</name></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><name sortKey="Niederwieser, Dietger" sort="Niederwieser, Dietger" uniqKey="Niederwieser D" first="Dietger" last="Niederwieser">Dietger Niederwieser</name></country><country name="Italie"><noRegion><name sortKey="Baccarani, Michele" sort="Baccarani, Michele" uniqKey="Baccarani M" first="Michele" last="Baccarani">Michele Baccarani</name></noRegion></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="Royaume-Uni"><region name="Angleterre"><name sortKey="Apperley, Jane F" sort="Apperley, Jane F" uniqKey="Apperley J" first="Jane F." last="Apperley">Jane F. Apperley</name></region></country><country name="France"><region name="Hauts-de-France"><name sortKey="Facon, Thierry" sort="Facon, Thierry" uniqKey="Facon T" first="Thierry" last="Facon">Thierry Facon</name></region></country><country name="Espagne"><region name="Catalogne"><name sortKey="Cervantes, Francisco" sort="Cervantes, Francisco" uniqKey="Cervantes F" first="Francisco" last="Cervantes">Francisco Cervantes</name></region></country><country name="Australie"><noRegion><name sortKey="Hughes, Timothy P" sort="Hughes, Timothy P" uniqKey="Hughes T" first="Timothy P." last="Hughes">Timothy P. Hughes</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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