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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 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 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 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 Neoplasia Oncogenes and Tumor Suppressors Free Research Articles 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 induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy Andreas Hochhaus1, Hagop M. Kantarjian2, Michele Baccarani3, Jeffrey H. Lipton4, Jane F. Apperley5, Brian J. Druker6, Thierry Facon7, Stuart L. Goldberg8, Francisco Cervantes9, Dietger Niederwieser10, Richard T. Silver11, Richard M. Stone12, Timothy P. Hughes13, Martin C. Muller1, Rana Ezzeddine14, Athena M. Countouriotis14, and Neil P. Shah15 1 III. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany; 2 Department of Leukemia, M.D. Anderson Cancer Center, Houston, TX; 3 Department of Hematology-Oncology "Seràgnoli," S Orsola-Malpighi University Hospital, University of Bologna, Italy; 4 Princess Margaret Hospital, Toronto, ON, Canada; 5 Department of Haematology, Hammersmith Hospital, London, United Kingdom; 6 Division of Hematology and Medical Oncology, Oregon Health Science University, Portland; 7 Hópital Claude Huriez, Lille, France; 8 Cancer Center, Hackensack University Medical Center, NJ; 9 Department of Hematology, Hospital Clinic, Barcelona, Spain; 10 Medizinische Klinik und Poliklinik II, Universitätsklinikum Leipzig, Germany; 11 Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY; 12 Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA; 13 Division of Hematology, Institute of Medical and Veterinary Science, Adelaide, Australia; 14 Bristol-Myers Squibb, Wallingford, CT; 15 Division of Hematology and Oncology, University College of San Francisco School of Medicine, CA Although imatinib induces marked responses in patients with chronic myeloid leukemia (CML), resistance is increasingly problematic, and treatment options for imatinib-resistant or -intolerant CML are limited. Dasatinib, a novel, highly potent, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, induced cytogenetic responses in a phase 1 study in imatinib-resistant or -intolerant CML and was well tolerated. Initial results are presented from a phase 2 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 twice daily). At 8-months' follow-up, dasatinib induced notable responses, with 90% and 52% of patients achieving complete hematologic and major cytogenetic responses (MCyR), respectively. Responses were long lasting: 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. Nonhematologic 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 responses in imatinib-resistant or -intolerant CML-CP, is well tolerated, and represents a promising therapeutic option for these patients. This trial was registered at www.clinicaltrials.gov as CA180013 [GenBank] . 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: 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. 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