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https://hdl.handle.net/2440/58773
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dc.contributor.author | Muller, M. | - |
dc.contributor.author | Cortes, J. | - |
dc.contributor.author | Kim, D. | - |
dc.contributor.author | Druker, B. | - |
dc.contributor.author | Erben, P. | - |
dc.contributor.author | Pasquini, R. | - |
dc.contributor.author | Branford, S. | - |
dc.contributor.author | Hughes, T. | - |
dc.contributor.author | Radich, J. | - |
dc.contributor.author | Ploughman, L. | - |
dc.contributor.author | Mukhopadhyay, J. | - |
dc.contributor.author | Hochhaus, A. | - |
dc.date.issued | 2009 | - |
dc.identifier.citation | Blood, 2009; 114(24):4944-4953 | - |
dc.identifier.issn | 0006-4971 | - |
dc.identifier.issn | 1528-0020 | - |
dc.identifier.uri | http://hdl.handle.net/2440/58773 | - |
dc.description.abstract | Dasatinib is a BCR-ABL inhibitor with 325-fold higher potency than imatinib against unmutated BCR-ABL in vitro. Imatinib failure is commonly caused by BCR-ABL mutations. Here, dasatinib efficacy was analyzed in patients recruited to phase 2/3 trials with chronic-phase chronic myeloid leukemia with or without BCR-ABL mutations after prior imatinib. Among 1043 patients, 39% had a preexisting BCR-ABL mutation, including 48% of 805 patients with imatinib resistance or suboptimal response. Sixty-threedifferent BCR-ABL mutations affecting 49 amino acids were detected at baseline, with G250, M351, M244, and F359 most frequently affected. After 2 years of follow-up, dasatinib treatment of imatinib-resistant patients with or without a mutation resulted in notable response rates (complete cytogenetic response: 43% vs 47%) and durable progression-free survival (70% vs 80%). High response rates were achieved with different mutations except T315I, including highly imatinib-resistant mutations in the P-loop region. Impaired responses were observed with some mutations with a dasatinib median inhibitory concentration (IC₅₀) greater than 3nM; among patients with mutations with lower or unknown IC₅₀, efficacy was comparable with those with no mutation. Overall, dasatinib has durable efficacy in patients with or without BCR-ABL mutations. | - |
dc.description.statementofresponsibility | Martin C. Müller, Jorge E. Cortes, Dong-Wook Kim, Brian J. Druker, Philipp Erben, Ricardo Pasquini, Susan Branford, Timothy P. Hughes, Jerald P. Radich, Lynn Ploughman, Jaydip Mukhopadhyay, and Andreas Hochhaus | - |
dc.language.iso | en | - |
dc.publisher | Amer Soc Hematology | - |
dc.rights | © 2009 by The American Society of Hematology | - |
dc.source.uri | http://dx.doi.org/10.1182/blood-2009-04-214221 | - |
dc.subject | Humans | - |
dc.subject | Pyrimidines | - |
dc.subject | Thiazoles | - |
dc.subject | Fusion Proteins, bcr-abl | - |
dc.subject | Protein Kinase Inhibitors | - |
dc.subject | Treatment Outcome | - |
dc.subject | DNA Mutational Analysis | - |
dc.subject | Mutation | - |
dc.subject | Adolescent | - |
dc.subject | Adult | - |
dc.subject | Aged | - |
dc.subject | Aged, 80 and over | - |
dc.subject | Middle Aged | - |
dc.subject | Female | - |
dc.subject | Male | - |
dc.subject | Leukemia, Myelogenous, Chronic, BCR-ABL Positive | - |
dc.subject | Randomized Controlled Trials as Topic | - |
dc.subject | Clinical Trials, Phase II as Topic | - |
dc.subject | Clinical Trials, Phase III as Topic | - |
dc.subject | Young Adult | - |
dc.subject | Kaplan-Meier Estimate | - |
dc.subject | Dasatinib | - |
dc.title | Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1182/blood-2009-04-214221 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Branford, S. [0000-0002-1964-3626] [0000-0002-5095-7981] | - |
dc.identifier.orcid | Hughes, T. [0000-0002-0910-3730] [0000-0002-7990-4509] | - |
Appears in Collections: | Aurora harvest Medicine publications |
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