SEARCH:   Advanced

Blood, 1 October 2007, Vol. 110, No. 7, pp. 2309-2315. Prepublished online as a Blood First Edition Paper on May 11, 2007; DOI 10.1182/blood-2007-02-073528. This Article Full Text (PDF) All Versions of this Article: blood-2007-02-073528v1 110/7/2309    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 Ottmann, O. Articles by Coutre, S. Search for Related Content PubMed PubMed Citation Articles by Ottmann, O. Articles by Coutre, S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 9, 2007 Accepted April 14, 2007 Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a Phase II study Oliver Ottmann*, Herve Dombret, Giovanni Martinelli, Bengt Simonsson, Francois Guilhot, Richard A Larson, Giovanna Rege-Cambrin, Jerald Radich, Andreas Hochhaus, Anne Marie Apanovitch, Ashwin Gollerkeri, and Steven Coutre Medizinische Klinik II, Johann Wolfgang Goethe Universitat, Frankfurt, Germany Hospital Saint Louis, Paris, France Istituto di Ematologica E Oncologica Medica, Policlinico S Orsola, Bologna, Italy Dept of Hematology, University Hospital, Uppsala, Sweden Clinical Research Centre, CHU la Miletrie, Poitiers, France University of Chicago, Chicago, IL, United States Dipartimento di Medicina Interna ii ed Ematologia, Azienda Ospedaliera S.Luigi, Orbassano, Italy Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States Medizinische Fakultat Mannheim, Universitat Heidelberg, Mannheim, Germany Bristol-Myers Squibb, Hopewell, NJ, United States Bristol-Myers Squibb, Wallingford, CT, United States Stanford University School of Medicine, Stanford, CA, United States * Corresponding author; email: ottmann{at}em.uni-frankfurt.de. Patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) generally have a rapid disease course and a poor overall prognosis. Dasatinib, a novel, oral, multi-targeted kinase inhibitor of BCR-ABL and SRC family kinases, has previously induced responses in patients with imatinib-resistant or -intolerant Ph-positive ALL. Here, we present the interim results of a Phase II study designed to further assess the efficacy, safety, and tolerability of dasatinib 140 mg in this patient population (N=36). With a minimum follow-up of 8 months, treatment with dasatinib resulted in substantial hematologic and cytogenetic response rates. Major hematologic responses were achieved in 42% of patients (15/36 patients), 67% of whom remained progression-free. Complete cytogenetic responses were attained by 58% of patients (21/36). Importantly, the presence of BCR-ABL mutations conferring imatinib-resistance did not preclude a response to dasatinib. Dasatinib was also tolerable, with 6% of patients (2/36) discontinuing therapy as a result of study-drug toxicity. Most adverse events (AEs) were Grade 1 or 2; febrile neutropenia was the most frequent severe AE, but this and other cytopenias were manageable with dose reduction. Dasatinib represents a safe and effective treatment option and represents an important therapeutic advance for patients with Ph-positive ALL. 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] K. R. Schultz, W. P. Bowman, A. Aledo, W. B. Slayton, H. Sather, M. Devidas, C. Wang, S. M. Davies, P. S. Gaynon, M. Trigg, et al. Improved Early Event-Free Survival With Imatinib in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Children's Oncology Group Study J. Clin. Oncol., November 1, 2009; 27(31): 5175 - 5181. [Abstract] [Full Text] [PDF] S. Mustjoki, S. Hernesniemi, A. Rauhala, M. Kahkonen, A. Almqvist, T. Lundan, and K. Porkka A novel dasatinib-sensitive RCSD1-ABL1 fusion transcript in chemotherapy-refractory adult pre-B lymphoblastic leukemia with t(1;9)(q24;q34) Haematologica, October 1, 2009; 94(10): 1469 - 1471. [Full Text] [PDF] 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. Evans Phase I Dose-Escalation and Pharmacokinetic Study of Dasatinib in Patients with Advanced Solid Tumors Clin. Cancer Res., October 1, 2009; 15(19): 6232 - 6240. [Abstract] [Full Text] [PDF] Y. Chen, S. Agarwal, N. M. Shaik, C. Chen, Z. Yang, and W. F. Elmquist P-glycoprotein and Breast Cancer Resistance Protein Influence Brain Distribution of Dasatinib J. Pharmacol. Exp. Ther., September 1, 2009; 330(3): 956 - 963. [Abstract] [Full Text] [PDF] J. F. Apperley, J. E. Cortes, D.-W. Kim, L. Roy, G. J. Roboz, G. Rosti, E. O. Bullorsky, E. Abruzzese, A. Hochhaus, D. Heim, et al. Dasatinib in the Treatment of Chronic Myeloid Leukemia in Accelerated Phase After Imatinib Failure: The START A Trial J. Clin. Oncol., July 20, 2009; 27(21): 3472 - 3479. [Abstract] [Full Text] [PDF] H. Kantarjian, J. Cortes, D.-W. Kim, P. Dorlhiac-Llacer, R. Pasquini, J. DiPersio, M. C. Muller, J. P. Radich, H. J. Khoury, N. Khoroshko, et al. Phase 3 study of dasatinib 140 mg once daily versus 70 mg twice daily in patients with chronic myeloid leukemia in accelerated phase resistant or intolerant to imatinib: 15-month median follow-up Blood, June 18, 2009; 113(25): 6322 - 6329. [Abstract] [Full Text] [PDF] N.V. Rajeshkumar, A. C. Tan, E. De Oliveira, C. Womack, H. Wombwell, S. Morgan, M. V. Warren, J. Walker, T. P. Green, A. Jimeno, et al. Antitumor Effects and Biomarkers of Activity of AZD0530, a Src Inhibitor, in Pancreatic Cancer Clin. Cancer Res., June 15, 2009; 15(12): 4138 - 4146. [Abstract] [Full Text] [PDF] T. Eley, F. R. Luo, S. Agrawal, A. Sanil, J. Manning, T. Li, A. Blackwood-Chirchir, and R. Bertz Phase I Study of the Effect of Gastric Acid pH Modulators on the Bioavailability of Oral Dasatinib in Healthy Subjects J. Clin. Pharmacol., June 1, 2009; 49(6): 700 - 709. [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] A. K. Fielding, J. M. Rowe, S. M. Richards, G. Buck, A. V. Moorman, I. J. Durrant, D. I. Marks, A. K. McMillan, M. R. Litzow, H. M. Lazarus, et al. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993 Blood, May 7, 2009; 113(19): 4489 - 4496. [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] J. S. Lagas, R. A.B. van Waterschoot, V. A.C.J. van Tilburg, M. J. Hillebrand, N. Lankheet, H. Rosing, J. H. Beijnen, and A. H. Schinkel Brain Accumulation of Dasatinib Is Restricted by P-Glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2) and Can Be Enhanced by Elacridar Treatment Clin. Cancer Res., April 1, 2009; 15(7): 2344 - 2351. [Abstract] [Full Text] [PDF] S.-F. Wong Dasatinib dosing strategies in Philadelphia chromosome-positive leukemia Journal of Oncology Pharmacy Practice, March 1, 2009; 15(1): 17 - 27. [Abstract] [PDF] S. M. O'Brien, D. A. Thomas, and S. Faderl A La Carte Therapy of Specific Acute Lymphocytic Leukemia Subsets ASCO Educational Book, January 1, 2009; 2009(1): 365 - 370. [Abstract] [Full Text] [PDF] P. Rousselot, J.-M. Cayuela, C. Recher, T. Leguay, C. Salanoubat, F. Witz, M. Alexis, M. Janvier, M. Hunault, P. Agape, et al. Dasatinib (Sprycel(R)) and Chemotherapy for First-Line Treatment in Elderly Patients with De Novo Philadelphia Positive ALL: Results of the First 22 Patients Included in the EWALL-Ph-01 Trial (on Behalf of the European Working Group on Adult ALL (EWALL)) Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 2920 - 2920. [Abstract] A. Giannoudis, A. Davies, C. M. Lucas, R. J. Harris, M. Pirmohamed, and R. E. Clark Effective dasatinib uptake may occur without human organic cation transporter 1 (hOCT1): implications for the treatment of imatinib-resistant chronic myeloid leukemia Blood, October 15, 2008; 112(8): 3348 - 3354. [Abstract] [Full Text] [PDF] 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] A. Fabarius, M. Giehl, B. Rebacz, A. Kramer, O. Frank, C. Haferlach, P. Duesberg, R. Hehlmann, W. Seifarth, and A. Hochhaus Centrosome aberrations and G1 phase arrest after in vitro and in vivo treatment with the SRC/ABL inhibitor dasatinib Haematologica, August 1, 2008; 93(8): 1145 - 1154. [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] D. K. Hiwase, V. Saunders, D. Hewett, A. Frede, S. Zrim, P. Dang, L. Eadie, L. B. To, J. Melo, S. Kumar, et al. Dasatinib Cellular Uptake and Efflux in Chronic Myeloid Leukemia Cells: Therapeutic Implications Clin. Cancer Res., June 15, 2008; 14(12): 3881 - 3888. [Abstract] [Full Text] [PDF] J. G. Harb, B. I. Chyla, and C. S. Huettner Loss of Bcl-x in Ph+ B-ALL increases cellular proliferation and does not inhibit leukemogenesis Blood, April 1, 2008; 111(7): 3760 - 3769. [Abstract] [Full Text] [PDF] A. Fielding The Treatment of Adults with Acute Lymphoblastic Leukemia Hematology, January 1, 2008; 2008(1): 381 - 389. [Abstract] [Full Text] [PDF] M. Wetzler Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia: On Target to Improve Outcome ASCO Educational Book, January 1, 2008; 2008(1): 275 - 279. [Abstract] [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020