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Blood, 15 March 2007, Vol. 109, No. 6, pp. 2303-2309. Prepublished online as a Blood First Edition Paper on November 30, 2006; DOI 10.1182/blood-2006-09-047266. This Article Full Text (PDF) Erratum (v110,p1438) All Versions of this Article: blood-2006-09-047266v1 109/6/2303    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 Hochhaus, A. Articles by Shah, N. P Search for Related Content PubMed PubMed Citation Articles by Hochhaus, A. Articles by Shah, N. P Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 15, 2006 Accepted November 1, 2006 Dasatinib induces notable hematologic and cytogenetic responses in chronic phase chronic myeloid leukemia after failure of imatinib therapy Andreas Hochhaus*, Hagop M Kantarjian, Michele Baccarani, Jeffrey H Lipton, Jane F Apperley, Brian J Druker, Thierry Facon, Stuart L Goldberg, Francisco Cervantes, Dietger Niederwieser, Richard T Silver, Richard M Stone, Timothy P Hughes, Martin C Muller, Rana Ezzeddine, Athena M Countouriotis, and Neil P Shah III. Medizinische Klinik, Medizinische Fakultat Mannheim, Universitat Heidelberg, Mannheim, Germany Department of Leukemia, MD Anderson Cancer Center, Houston, TX, United States Department of Hematology-Oncology "Seragnoli", S Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy Princess Margaret Hospital, Ontario, Canada Department of Haematology, Hammersmith Hospital, London, United Kingdom Division of Hematology and Medical Oncology, Oregon Health Science University, Portland, OR, United States Hopital Claude Huriez, Lille, France Cancer Center, Hackensack University Medical Center, Hackensack, NJ, United States Department of Hematology, Hospital Clinic, Barcelona, Spain Medizinische Klinik und Poliklinik II, Universitatsklinikum Leipzig, Leipzig, Germany Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY, United States Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA, United States Division of Hematology, Institute of Medical and Veterinary Science, Adelaide, Australia Bristol-Myers Squibb, Wallingford, CT, United States Division of Hematolgoy and Oncology, University College of San Francisco School of Medicine, San Francisco, CA, United States * Corresponding author; email: nicola.turner{at}gcus.thomson.com. Although imatinib induces marked responses in patients with chronic myeloid leukemia (CML), resistance is increasingly problematic, and treatment options for imatinib-resistant/-intolerant CML are limited. Dasatinib, a novel, highly potent, oral, multi-targeted kinase inhibitor of BCR-ABL and SRC family kinases, induced cytogenetic responses in a Phase-I study in imatinib-resistant/-intolerant CML, and was well tolerated. Initial results are presented from a Phase-II study of 186 patients with imatinib-resistant or -intolerant chronic phase CML (CML-CP) designed to further establish the efficacy and safety of dasatinib (70 mg BID). At 8-months' follow-up, dasatinib induced notable responses, with 52% and 90% of patients achieving major cytogenetic (MCyR) and complete hematologic responses, respectively. Responses were durable: only 2% of patients achieving MCyR progressed or died. Importantly, comparable responses were achieved by patients carrying BCR-ABL mutations conferring imatinib resistance. Dasatinib also induced molecular responses, reducing BCR-ABL:ABL transcript ratios from 66% at baseline to 2.6% at 9 months. Non-hematologic adverse events were generally mild-to-moderate, and most cytopenias were effectively managed with dose modifications. Cross-intolerance with imatinib was not evident. To conclude, dasatinib induces notable, durable responses in imatinib-resistant or -intolerant CML-CP, is well tolerated, and represents a promising therapeutic option for these patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Closing the gap in CML Jacob M. Rowe Blood 2007 109: 2271. [Full Text] [PDF] This article has been cited by other articles: G. D. Demetri, P. Lo Russo, I. R.J. MacPherson, D. Wang, J. A. Morgan, V. G. Brunton, P. Paliwal, S. Agrawal, M. Voi, and T.R. J. 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