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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4143-4150. Prepublished online as a Blood First Edition Paper on January 30, 2007; DOI 10.1182/blood-2006-09-046839. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-09-046839v1 109/10/4143    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Guilhot, F. Articles by Talpaz, M. Search for Related Content PubMed PubMed Citation Articles by Guilhot, F. Articles by Talpaz, M. Related Collections Oncogenes and Tumor Suppressors Free Research Articles Clinical Trials and Observations Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase Francois Guilhot1, Jane Apperley2, Dong-Wook Kim3, Eduardo O. Bullorsky4, Michele Baccarani5, Gail J. Roboz6, Sergio Amadori7, Carmino A. de Souza8, Jeffrey H. Lipton9, Andreas Hochhaus10, Dominik Heim11, Richard A. Larson12, Susan Branford13, Martin C. Muller10, Prasheen Agarwal14, Ashwin Gollerkeri14, and Moshe Talpaz15 1 Clinical Research Centre, Centre Hospitalier et Universitaire (CHU) La Miletrie, Poitiers, France; 2 Hammersmith Hospital, London, United Kingdom; 3 St Mary's Hospital, The Catholic University of Korea, Seoul, Korea; 4 Department of Hematology and Bone Marrow Transplantation, British Hospital of Buenos Aires, Buenos Aires, Argentina; 5 Istituto di Ematologica E Oncologica Medica, Policlinico S. Orsola, Bologna, Italy; 6 Weill Medical College-Cornell University, New York Presbyterian Hospital, New York, NY; 7 Ospedale S. Eugenio, Divisione di Ematologia, Roma, Italy; 8 Universidade Estadual De Campinas, Campinas, Brazil; 9 Princess Margaret Hospital, Toronto, ON, Canada; 10 Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany; 11 Department of Hematology, University Hospital, Basel, Switzerland; 12 University of Chicago, Chicago, IL; 13 Division of Hematology, Institute of Medical and Veterinary Science, Adelaide, Australia; 14 Bristol-Myers Squibb, Wallingford, CT; 15 Department of Leukemia, M.D. Anderson Cancer Center, Houston, TX 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Dasatinib in accelerated phase Stephen O'Brien Blood 2007 109: 4110. [Full Text] [PDF] This article has been cited by other articles: N. P. Shah, H. M. Kantarjian, D.-W. Kim, D. Rea, P. E. Dorlhiac-Llacer, J. H. Milone, J. Vela-Ojeda, R. T. Silver, H. J. Khoury, A. Charbonnier, et al. Intermittent Target Inhibition With Dasatinib 100 mg Once Daily Preserves Efficacy and Improves Tolerability in Imatinib-Resistant and -Intolerant Chronic-Phase Chronic Myeloid Leukemia J. Clin. Oncol., July 1, 2008; 26(19): 3204 - 3212. [Abstract] [Full Text] [PDF] G. 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Carayol, E. Katsoulidis, A. Sassano, J. K. Altman, B. J. Druker, and L. C. Platanias Suppression of Programmed Cell Death 4 (PDCD4) Protein Expression by BCR-ABL-regulated Engagement of the mTOR/p70 S6 Kinase Pathway J. Biol. Chem., March 28, 2008; 283(13): 8601 - 8610. [Abstract] [Full Text] [PDF] M. Kneidinger, U. Schmidt, U. Rix, K. V. Gleixner, A. Vales, C. Baumgartner, C. Lupinek, M. Weghofer, K. L. Bennett, H. Herrmann, et al. The effects of dasatinib on IgE receptor-dependent activation and histamine release in human basophils Blood, March 15, 2008; 111(6): 3097 - 3107. [Abstract] [Full Text] [PDF] P. le Coutre, O. G. Ottmann, F. Giles, D.-W. Kim, J. Cortes, N. Gattermann, J. F. Apperley, R. A. Larson, E. Abruzzese, S. G. O'Brien, et al. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia Blood, February 15, 2008; 111(4): 1834 - 1839. 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Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study Blood, October 1, 2007; 110(7): 2309 - 2315. [Abstract] [Full Text] [PDF] T. O'Hare, C. A. Eide, and M. W. N. Deininger Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia Blood, October 1, 2007; 110(7): 2242 - 2249. [Abstract] [Full Text] [PDF] E. L. Kwak, J. W. Clark, and B. Chabner Targeted Agents: The Rules of Combination Clin. Cancer Res., September 15, 2007; 13(18): 5232 - 5237. [Abstract] [Full Text] [PDF] A. Quintas-Cardama, H. Kantarjian, S. O'Brien, G. Borthakur, J. Bruzzi, R. Munden, and J. Cortes Pleural Effusion in Patients With Chronic Myelogenous Leukemia Treated With Dasatinib After Imatinib Failure J. Clin. Oncol., September 1, 2007; 25(25): 3908 - 3914. [Abstract] [Full Text] [PDF] C. A. 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