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Blood, 15 November 2007, Vol. 110, No. 10, pp. 3540-3546. Prepublished online as a Blood First Edition Paper on August 22, 2007; DOI 10.1182/blood-2007-03-080689. This Article Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2007-03-080689v1 110/10/3540    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. M Articles by le Coutre, P. Search for Related Content PubMed PubMed Citation Articles by Kantarjian, H. M Articles by le Coutre, P. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 19, 2007 Accepted July 27, 2007 Nilotinib (formerly AMN107), a highly selective Bcr-Abl tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance Hagop M Kantarjian*, Francis Giles, Norbert Gattermann, Kapil Bhalla, Giuliana Alimena, Francesca Palandri, Gert J Ossenkoppele, Franck-Emmanuel Nicolini, Stephen G O'Brien, Mark Litzow, Ravi Bhatia, Francisco Cervantes, Ariful Haque, Yaping Shou, Debra J Resta, Aaron Weitzman, Andreas Hochhaus, and Philipp le Coutre Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, TX, United States Department of Hematology, Universitaetsklinikum, Duesseldorf, Germany Department of Hematology, H. Lee Moffitt Cancer Center, Tampa, FL, United States Azienda Policlinico Umberto I, Universita "La Sapienza", Rome, Italy S Orsola - Malpighi University Hospital, University of Bologna, Bologna, Italy Department of Hematology, VU Medisch Centrum, Amsterdam, Netherlands Department of Hematology, Hopital Edouard Herriot, Lyon, France Department of Hematology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom College of Medicine, Mayo Clinic, Rochester, MN, United States Department of Hematology, City of Hope National Medical Center, Duarte, CA, United States Department of Hematology, Hospital Clinic, Barcelona, Spain Department of Hematology, Novartis Pharmaceuticals, Florham Park, NJ, United States III Medizinische Klinik, Medizinische Facultat Mannheim, Universitat Heidelberg, Mannheim, Germany Campus Virchow Klinikum, Charite, Humboldt-Universitat, Berlin, Germany * Corresponding author; email: hkantarj{at}mdanderson.org. Nilotinib, an orally bioavailable, selective Bcr-Abl tyrosine kinase inhibitor, is 30-fold more potent than imatinib in preclinical models, and overcomes most imatinib resistant BCR-ABL mutations. In this phase II open-label study, nilotinib 400 mg was administered orally twice daily to 280 patients with Philadelphia chromosome (Ph)-positive chronic myeloid leukemia in chronic phase after imatinib failure or intolerance. Patients had at least six months of follow-up and were evaluated for hematologic and cytogenetic responses, as well as for safety and overall survival. At six months, the rate of major cytogenetic response (Ph 35%) was 48%: complete (Ph 0%) in 31%, and partial (Ph 1-35%) in 16%. The estimated survival at 12 months was 95%. Nilotinib was effective in patients harboring BCR-ABL mutations associated with imatinib resistance (except T315I), and also in patients with a resistance mechanism independent of BCR-ABL mutations. Adverse events were mostly mild to moderate, and there was minimal cross-intolerance with imatinib. Grade 3-4 neutropenia and thrombocytopenia were observed in 29% of patients; pleural or pericardial effusions were observed in 1% (none severe). In summary, nilotinib is highly active and safe in patients with CML-CP post imatinib failure or intolerance. This clinical trial is registered at http://clinicaltrials.gov as ID#NCT00109707. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. J. Garg, H. Kantarjian, S. O'Brien, A. Quintas-Cardama, S. Faderl, Z. Estrov, and J. Cortes The use of nilotinib or dasatinib after failure to 2 prior tyrosine kinase inhibitors: long-term follow-up Blood, November 12, 2009; 114(20): 4361 - 4368. [Abstract] [Full Text] [PDF] T. Hughes, G. Saglio, S. Branford, S. Soverini, D.-W. Kim, M. C. Muller, G. Martinelli, J. Cortes, L. Beppu, E. Gottardi, et al. 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