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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 15, 2006 Accepted January 20, 2007 Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase Francois Guilhot*, Jane Apperley, Dong-Wook Kim, Eduardo O Bullorsky, Michele Baccarani, Gail J Roboz, Sergio Amadori, Carmino A de Souza, Jeffrey H Lipton, Andreas Hochhaus, Dominik Heim, Richard A Larson, Susan Branford, Martin C Muller, Prasheen Agarwal, Ashwin Gollerkeri, and Moshe Talpaz Clinical Research Centre, CHU La Miletrie, Poitiers, France Hammersmith Hospital, London, United Kingdom St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea, Republic of Dept of Hematology & Bone Marrow Transplantation, British Hospital of Buenos Aires, Buenos Aires, Argentina Istituto di Ematologica E Oncologica Medica, Policlinico S Orsola, Bologna, Italy Weill Medical College-Cornell University, New York Presbyterian Hospital, New York, NY, United States Divisione di Ematologia, Ospedale S. Eugenio, Rome, Italy Universidade Estadual De Campinas, Campinas, Brazil Princess Margaret Hospital, Toronto, Ontario, Canada Medizinische Fakultat Mannheim, Universitat Heidelberg, Mannheim, Germany Dept of Hematology, University Hospital, Basel, Switzerland University of Chicago, Chicago, IL, United States Division of Hematology, Institute of Medical and Veterinary Science, Adelaide, Australia Bristol-Myers Squibb, Wallingford, CT, United States Dept of Leukemia, MD Anderson Cancer Center, Houston, TX, United States * Corresponding author; email: f.guilhot{at}chu-poitiers.fr. Treatment options are limited for patients with imatinib-resistant or -intolerant accelerated-phase chronic myeloid leukemia (CML-AP). Dasatinib is a novel, potent, oral, multi-targeted kinase inhibitor of BCR-ABL and SRC-family kinases that showed marked efficacy in a Phase I trial of imatinib-resistant CML patients. Results are presented for 107 CML-AP patients with imatinib-resistance and -intolerance from a Phase II, 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, while 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 non-hematologic adverse events (AEs) were mild-to-moderate; no imatinib-intolerant patients discontinued dasatinib due to 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. 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: 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] G. Giaccone and P. A. Zucali Src as a potential therapeutic target in non-small-cell lung cancer Ann. Onc., July 1, 2008; 19(7): 1219 - 1223. [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] 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. 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