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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 6, 2006 Accepted February 13, 2007 Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase-II trial Hagop Kantarjian*, Ricardo Pasquini, Nelson Hamerschlak, Philippe Rousselot, Jerzy Holowiecki, Saengsuree Jootar, Tadeusz Robak, Nina Khoroshko, Tamas Masszi, Aleksander Skotnicki, Andrzej Hellmann, Andrey Zaritsky, Anatoly Golenkov, Jerald Radich, Timothy Hughes, Athena Countouriotis, and Neil Shah MD Anderson Cancer Center, Houston, TX, United States Hospital De Clinicas De Curitiba, Curitiba, Brazil Hospital Israelita Albert Einstein, Sao Paulo, Brazil Hospital Saint Louis, Paris Cedex, France Katedra I Klinika Hematologii I Transplantacji Szpiku, Katowice, Poland Ramathibodi Hospital, Bankok, Thailand Szpital Specjalistyczny Im. Kopernika Klinika Hematologii, Lodz, Poland National Research Hematology Center, Moscow, Russian Federation National Medical Center, Budapest, Hungary Katedra I Klinika Hematologii, CMUJ, Gdansk, Poland Klinika Hematologii, Akademia Medyczna, Gdansk, Poland St Petersburg State Medical University, St Petersburg, Russian Federation Moscow Region Research Clinical Institute, Moscow, Russian Federation Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States Division of Hematology, Institute of Medical and Veterinary Science, Adelaide, Australia Bristol-Myers Squibb, Wallingford, CT, United States Division of Hematology and Oncology, University College of San Francisco School of Medicine, San Francisco, CA, United States * Corresponding author; email: hkantarj{at}mdanderson.org. Therapeutic options for chronic myelogenous leukemia (CML) resistant to imatinib 400-600 mg are limited. Escalating imatinib doses may overcome resistance and dasatinib, a significantly more potent inhibitor of BCR-ABL, is also safe and effective in this population. Patients with imatinib-resistant chronic-phase (CP) CML were randomized (2:1) to dasatinib 140 mg (n=101) or imatinib 800 mg (n=49). With median follow-up of 15 months, complete hematologic responses were observed in 93% and 82% of patients receiving dasatinib and high-dose imatinib (P=0.034). Dasatinib resulted in higher major cytogenetic response rates (52%) than high-dose imatinib (33%) (P=0.023); this included complete cytogenetic response in 40% and 16% (P=0.004). Major molecular responses were also more frequent with dasatinib (16% vs. 4%; P=0.038). Treatment failure (hazard ratio [HR], 0.16; P<0.0001) and progression-free survival (HR, 0.14; P<0.0001) both favored dasatinib. Superficial edema (42% vs. 15%) and fluid retention (45% vs. 30%) were more prevalent with imatinib; pleural effusion was more common with dasatinib (17% vs. 0%). Grade 3-4 non-hematologic 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: K. Porkka, P. Koskenvesa, T. Lundan, J. Rimpilainen, S. Mustjoki, R. Smykla, R. Wild, R. Luo, M. Arnan, B. Brethon, et al. Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia Blood, August 15, 2008; 112(4): 1005 - 1012. [Abstract] [Full Text] [PDF] 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] D. K. Hiwase, V. Saunders, D. Hewett, A. Frede, S. Zrim, P. Dang, L. Eadie, L. B. To, J. Melo, S. Kumar, et al. Dasatinib Cellular Uptake and Efflux in Chronic Myeloid Leukemia Cells: Therapeutic Implications Clin. Cancer Res., June 15, 2008; 14(12): 3881 - 3888. [Abstract] [Full Text] [PDF] S. 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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