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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5143-5150. Prepublished online as a Blood First Edition Paper on February 22, 2007; DOI 10.1182/blood-2006-11-056028. This Article Full Text Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2006-11-056028v1 109/12/5143    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 Kantarjian, H. Articles by Shah, N. Search for Related Content PubMed PubMed Citation Articles by Kantarjian, H. Articles by Shah, N. Related Collections Neoplasia Oncogenes and Tumor Suppressors Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial Hagop Kantarjian1, Ricardo Pasquini2, Nelson Hamerschlak3, Philippe Rousselot4, Jerzy Holowiecki5, Saengsuree Jootar6, Tadeusz Robak7, Nina Khoroshko8, Tamas Masszi9, Aleksander Skotnicki10, Andrzej Hellmann11, Andrey Zaritsky12, Anatoly Golenkov13, Jerald Radich14, Timothy Hughes15, Athena Countouriotis16, and Neil Shah17 1 M. D. Anderson Cancer Center, Houston, TX; 2 Hospital De Clinicas De Curitiba, Curitiba, Parana, Brazil; 3 Hospital Israelita Albert Einstein, Sao Paulo, Brazil; 4 Hospital Saint Louis, Paris Cedex, France; 5 Katedra I Klinika Hematologii I Transplantacji Szpiku, Katowice, Poland; 6 Ramathibodi Hospital, Bangkok, Thailand; 7 Szpital Specjalistyczny Im. Kopernika Klinika Hematologii, Lodz, Poland; 8 National Research Hematology Center, Moscow, Russian Federation; 9 National Medical Center, Budapest, Hungary; 10 Collegium Medicum Uniwesytetu Jagiellonskiego, Krakow, Poland; 11 Klinika Hematologii, Akademia Medyczna, Gdansk, Poland; 12 St Petersburg State Medical University, St Petersburg, Russian Federation; 13 Moscow Region Research Clinical Institute, Moscow, Russia; 14 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; 15 Division of Hematology, Institute of Medical and Veterinary Science, Adelaide, Australia; 16 Bristol-Myers Squibb, Wallingford, CT; 17 Division of Hematology and Oncology, University College of San Francisco School of Medicine, San Francisco, CA Therapeutic options for chronic myelogenous leukemia (CML) resistant to 400 to 600 mg imatinib are limited. Escalating imatinib doses may overcome resistance. Dasatinib, a significantly more potent inhibitor of BCR-ABL, is safe and effective in this population. Patients with imatinib-resistant chronic-phase (CP) CML were randomized 2:1 to 140 mg dasatinib (n = 101) or 800 mg imatinib (n = 49). With a median follow up of 15 months, complete hematologic responses were observed in 93% and 82% of patients receiving dasatinib and high-dose imatinib (P = .034), respectively. Dasatinib resulted in higher major cytogenetic response rates (52%) than high-dose imatinib (33%) (P = .023); this included complete cytogenetic response in 40% and 16% (P = .004). Major molecular responses were also more frequent with dasatinib (16% versus 4%; P = 0.038). Treatment failure (hazard ratio [HR], 0.16; P < .001) and progression-free survival (HR, 0.14; P < .001) both favored dasatinib. Superficial edema (42% versus 15%) and fluid retention (45% versus 30%) were more prevalent with imatinib; pleural effusion was more common with dasatinib (17% versus 0%). Grade 3 to 4 nonhematologic toxicity was minimal. Cytopenias were more frequent and severe with dasatinib. Dasatinib represents a safe and effective therapy for CP-CML resistant to conventional imatinib doses with improved cytogenetic and molecular response rates and progression-free survival relative to high-dose imatinib. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: What if conventional-dose imatinib fails? Charles A. Schiffer Blood 2007 109: 5068-5069. [Full Text] [PDF] This article has been cited by other articles: J. L. Snead, T. O'Hare, L. T. Adrian, C. A. Eide, T. Lange, B. J. Druker, and M. W. Deininger Acute dasatinib exposure commits Bcr-Abl-dependent cells to apoptosis Blood, October 15, 2009; 114(16): 3459 - 3463. [Abstract] [Full Text] [PDF] Y. Chen, S. Agarwal, N. M. Shaik, C. Chen, Z. Yang, and W. F. 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Verstovsek, A. Tefferi, J. Cortes, S. O'Brien, G. Garcia-Manero, A. Pardanani, C. Akin, S. Faderl, T. Manshouri, D. Thomas, et al. 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] 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. Hantschel, U. Rix, U. Schmidt, T. Burckstummer, M. Kneidinger, G. Schutze, J. Colinge, K. L. Bennett, W. Ellmeier, P. Valent, et al. The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib PNAS, August 14, 2007; 104(33): 13283 - 13288. [Abstract] [Full Text] [PDF] C. A. Schiffer BCR-ABL Tyrosine Kinase Inhibitors for Chronic Myelogenous Leukemia N. Engl. J. Med., July 19, 2007; 357(3): 258 - 265. [Full Text] [PDF] S. O'Brien Dasatinib in accelerated phase Blood, May 15, 2007; 109(10): 4110 - 4110. [Full Text] [PDF]

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