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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3207-3213. Prepublished online as a Blood First Edition Paper on December 21, 2006; DOI 10.1182/blood-2006-09-046888. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-09-046888v1 109/8/3207    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 Cortes, J. Articles by Baccarani, M. Search for Related Content PubMed PubMed Citation Articles by Cortes, J. Articles by Baccarani, M. Related Collections Neoplasia Oncogenes and Tumor Suppressors Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis Jorge Cortes1, Philippe Rousselot2, Dong-Wook Kim3, Ellen Ritchie4, Nelson Hamerschlak5, Steven Coutre6, Andreas Hochhaus7, Francois Guilhot8, Giuseppe Saglio9, Jane Apperley10, Oliver Ottmann11, Neil Shah12, Philipp Erben7, Susan Branford13, Prasheen Agarwal14, Ashwin Gollerkeri14, and Michele Baccarani15 1 M. D. Anderson Cancer Center, Houston, TX; 2 Hospital Saint Louis, Centre d'Investigation Clinique, Paris, France; 3 Uijeongbu St Mary's Hospital, Kyunggi-Do, Republic of Korea; 4 Weill Medical College–Cornell University, New York Presbyterian Hospital, New York, NY; 5 Hospital Israelita Albert Einstein, Sao Paulo, Brazil; 6 Stanford University School of Medicine, Stanford, CA; 7 Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany; 8 Hôpital Jean Bernard, Poitiers, France; 9 Azienda Ospedaliera S. Luigi, Orbassano, Italy; 10 Hammersmith Hospital, London, United Kingdom; 11 Johann Wolfgang Goethe Universität, Frankfurt-am-Main, Germany; 12 University College of Los Angeles, CA; 13 Division of Hematology, Institute of Medical and Veterinary Science, Adelaide, Australia; 14 Bristol-Myers Squibb, Wallingford, CT; 15 Istituto di Ematologica E Oncologica Medica, Policlinico S. Orsola, Bologna, Italy 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Unraveling CML phase by phase John Goldman Blood 2007 109: 3128. [Full Text] [PDF] This article has been cited by other articles: H. Kantarjian, J. Cortes, D.-W. Kim, P. Dorlhiac-Llacer, R. 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Phase II Study of Dasatinib in Philadelphia Chromosome-Negative Acute and Chronic Myeloid Diseases, Including Systemic Mastocytosis Clin. Cancer Res., June 15, 2008; 14(12): 3906 - 3915. [Abstract] [Full Text] [PDF] R. Weichsel, C. Dix, L. Wooldridge, M. Clement, A. Fenton-May, A. K. Sewell, J. Zezula, E. Greiner, E. Gostick, D. A. Price, et al. Profound Inhibition of Antigen-Specific T-Cell Effector Functions by Dasatinib Clin. Cancer Res., April 15, 2008; 14(8): 2484 - 2491. [Abstract] [Full Text] [PDF] L. K. Kenealy, C. B. Christenson, and C. B. Williams Current Therapies for Chronic Myeloid Leukemia Journal of Pharmacy Practice, April 1, 2008; 21(2): 116 - 125. [Abstract] [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] D. S. Ritchie, M. McBean, D. A Westerman, S. Kovalenko, J. F. Seymour, and A. Dobrovic Complete molecular response of e6a2 BCR-ABL-positive acute myeloid leukemia to imatinib then dasatinib Blood, March 1, 2008; 111(5): 2896 - 2898. [Abstract] [Full Text] [PDF] H. M Marshall and J. M Hammond Treatment Options in Imatinib-Resistant Chronic Myelogenous Leukemia Ann. Pharmacother., February 1, 2008; 42(2): 259 - 264. [Abstract] [Full Text] [PDF] A. E. Schade, G. L. Schieven, R. Townsend, A. M. Jankowska, V. Susulic, R. Zhang, H. Szpurka, and J. P. Maciejewski Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation Blood, February 1, 2008; 111(3): 1366 - 1377. [Abstract] [Full Text] [PDF] J. E. Cortes Imatinib and Beyond--Therapy of CML in 2008 ASCO Educational Book, January 1, 2008; 2008(1): 307 - 312. [Abstract] [Full Text] [PDF] A. Bergeron, D. Rea, V. Levy, C. Picard, V. Meignin, J. Tamburini, H. Bruzzoni-Giovanelli, F. Calvo, A. Tazi, and P. Rousselot Lung Abnormalities after Dasatinib Treatment for Chronic Myeloid Leukemia: A Case Series Am. J. Respir. Crit. Care Med., October 15, 2007; 176(8): 814 - 818. [Abstract] [Full Text] [PDF] J. M. Goldman How I treat chronic myeloid leukemia in the imatinib era Blood, October 15, 2007; 110(8): 2828 - 2837. [Abstract] [Full Text] [PDF] O. Ottmann, H. Dombret, G. Martinelli, B. Simonsson, F. Guilhot, R. A. Larson, G. Rege-Cambrin, J. Radich, A. Hochhaus, A. M. Apanovitch, et al. 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] R. D. Loberg, D. A. Bradley, S. A. Tomlins, A. M. Chinnaiyan, and K. J. Pienta The Lethal Phenotype of Cancer: The Molecular Basis of Death Due to Malignancy CA Cancer J Clin, July 1, 2007; 57(4): 225 - 241. [Abstract] [Full Text] [PDF] H. Kantarjian, R. Pasquini, N. Hamerschlak, P. Rousselot, J. Holowiecki, S. Jootar, T. Robak, N. Khoroshko, T. Masszi, A. Skotnicki, et al. Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial Blood, June 15, 2007; 109(12): 5143 - 5150. [Abstract] [Full Text] [PDF] A. Fabarius, C. Haferlach, M. C. Muller, P. Erben, T. Lahaye, M. Giehl, O. Frank, W. Seifarth, R. Hehlmann, and A. 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