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Blood, 15 February 2008, Vol. 111, No. 4, pp. 1834-1839. Prepublished online as a Blood First Edition Paper on December 10, 2007; DOI 10.1182/blood-2007-04-083196. This Article Full Text Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2007-04-083196v1 blood-2007-04-083196v2 111/4/1834    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 le Coutre, P. Articles by Kantarjian, H. Search for Related Content PubMed PubMed Citation Articles by le Coutre, P. Articles by Kantarjian, H. Related Collections Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia Philipp le Coutre1, Oliver G. Ottmann2, Francis Giles3, Dong-Wook Kim4, Jorge Cortes3, Norbert Gattermann5, Jane F. Apperley6, Richard A. Larson7, Elisabetta Abruzzese8, Stephen G. O'Brien9, Kazimierz Kuliczkowski10, Andreas Hochhaus11, Francois-Xavier Mahon12, Giuseppe Saglio13, Marco Gobbi14, Yok-Lam Kwong15, Michele Baccarani16, Timothy Hughes17, Giovanni Martinelli16, Jerald P. Radich18, Ming Zheng19, Yaping Shou19, and Hagop Kantarjian3 1 Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Germany; 2 Johann Wolfgang Goethe-Universität, Frankfurt, Germany; 3 M. D. Anderson Cancer Center, Houston, TX; 4 St Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea; 5 Heinrich Heine University, Düsseldorf, Germany; 6 Hammersmith Hospital, London, United Kingdom; 7 University of Chicago Cancer Center, IL; 8 Ospedale San Eugenio, Tor Vergata University, Rome, Italy; 9 Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom; 10 Klinika Hematologii, Wroclaw, Poland; 11 Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany; 12 Hôpital Pellegrin, Bordeaux, France; 13 Ospedale San Luigi Gonzaga, Torino, Italy; 14 Ospedale San Martino, Genoa, Italy; 15 Queen Mary Hospital, Hong Kong, China; 16 Policlinico San Orsola Malpighi, Bologna, Italy; 17 Royal Adelaide Hospital, Adelaide, Australia; 18 Fred Hutchinson Cancer Research Center, Seattle, WA; and 19 Novartis Pharmaceuticals, East Hanover, NJ Patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia (CML-AP) have very limited therapeutic options. Nilotinib is a highly selective BCR-ABL tyrosine kinase inhibitor. This phase 2 trial was designed to characterize the efficacy and safety of nilotinib (400 mg twice daily) in this patient population with hematologic response (HR) as primary efficacy endpoint. A total of 119 patients were enrolled and had a median duration of treatment of 202 days (range, 2–611 days). An HR was observed in 56 patients (47%; 95% confidence interval [CI], 38%-56%). Major cytogenetic response (MCyR) was observed in 35 patients (29%; 95% CI, 21%-39%). The median duration of HR has not been reached. Overall survival rate among the 119 patients after 12 months of follow-up was 79% (95% CI, 70%-87%). Nonhematologic adverse events were mostly mild to moderate. Severe peripheral edema and pleural effusions were not observed. The most common grade 3 or higher hematologic adverse events were thrombocytopenia (35%) and neutropenia (21%). Grade 3 or higher bilirubin and lipase elevations occurred in 9% and 18% of patients, respectively, resulting in treatment discontinuation in one patient. In conclusion, nilotinib is an effective and well-tolerated treatment in imatinib-resistant and -intolerant CML-AP. This trial is registered at www.clinicaltrials.gov as NCT00384228 [ClinicalTrials.gov] . CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Martinelli, I. Iacobucci, C. T. Storlazzi, M. Vignetti, F. Paoloni, D. Cilloni, S. Soverini, A. Vitale, S. Chiaretti, G. Cimino, et al. IKZF1 (Ikaros) Deletions in BCR-ABL1-Positive Acute Lymphoblastic Leukemia Are Associated With Short Disease-Free Survival and High Rate of Cumulative Incidence of Relapse: A GIMEMA AL WP Report J. Clin. Oncol., November 1, 2009; 27(31): 5202 - 5207. [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. Impact of Baseline BCR-ABL Mutations on Response to Nilotinib in Patients With Chronic Myeloid Leukemia in Chronic Phase J. Clin. Oncol., September 1, 2009; 27(25): 4204 - 4210. [Abstract] [Full Text] [PDF] E. T.H. Yeh and C. L. Bickford Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J. Am. Coll. Cardiol., June 16, 2009; 53(24): 2231 - 2247. [Abstract] [Full Text] [PDF] C. Fava, H. M. Kantarjian, E. Jabbour, S. O'Brien, N. Jain, M. B. Rios, G. Garcia-Manero, F. Ravandi, S. Verstovsek, G. Borthakur, et al. Failure to achieve a complete hematologic response at the time of a major cytogenetic response with second-generation tyrosine kinase inhibitors is associated with a poor prognosis among patients with chronic myeloid leukemia in accelerated or blast phase Blood, May 21, 2009; 113(21): 5058 - 5063. [Abstract] [Full Text] [PDF] T. Tyler Once-Daily Dasatinib for Treatment of Patients with Chronic Myeloid Leukemia Ann. Pharmacother., May 1, 2009; 43(5): 920 - 927. [Abstract] [Full Text] [PDF] F. Palandri, F. Castagnetti, G. Alimena, N. Testoni, M. Breccia, S. Luatti, G. Rege-Cambrin, F. Stagno, G. Specchia, B. Martino, et al. The long-term durability of cytogenetic responses in patients with accelerated phase chronic myeloid leukemia treated with imatinib 600 mg: the GIMEMA CML Working Party experience after a 7-year follow-up Haematologica, February 1, 2009; 94(2): 205 - 212. [Abstract] [Full Text] [PDF] E. Jabbour, J. E. Cortes, and H. M. Kantarjian Suboptimal Response to or Failure of Imatinib Treatment for Chronic Myeloid Leukemia: What Is the Optimal Strategy? Mayo Clin. Proc., February 1, 2009; 84(2): 161 - 169. [Abstract] [Full Text] [PDF] T. O'Hare and M. W. Deininger Toward a Cure For Chronic Myeloid Leukemia Clin. Cancer Res., December 15, 2008; 14(24): 7971 - 7974. [Full Text] [PDF] B. J. Druker Translation of the Philadelphia chromosome into therapy for CML Blood, December 15, 2008; 112(13): 4808 - 4817. [Abstract] [Full Text] [PDF] D. Marin, D. Milojkovic, E. Olavarria, J. S. Khorashad, H. de Lavallade, A. G. Reid, L. Foroni, K. Rezvani, M. Bua, F. Dazzi, et al. European LeukemiaNet criteria for failure or suboptimal response reliably identify patients with CML in early chronic phase treated with imatinib whose eventual outcome is poor Blood, December 1, 2008; 112(12): 4437 - 4444. [Abstract] [Full Text] [PDF] F. L. Chen, W. Xia, and N. L. Spector Acquired Resistance to Small Molecule ErbB2 Tyrosine Kinase Inhibitors Clin. Cancer Res., November 1, 2008; 14(21): 6730 - 6734. [Abstract] [Full Text] [PDF] M. W. Deininger Milestones and Monitoring in Patients with CML Treated with Imatinib Hematology, January 1, 2008; 2008(1): 419 - 426. [Abstract] [Full Text] [PDF] C. H. Jamieson Chronic Myeloid Leukemia Stem Cells Hematology, January 1, 2008; 2008(1): 436 - 442. [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]

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