SEARCH:   Advanced

Blood, 1 February 2005, Vol. 105, No. 3, pp. 940-947. Prepublished online as a Blood First Edition Paper on October 14, 2004; DOI 10.1182/blood-2004-05-1933. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-05-1933v1 105/3/940    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 Faderl, S. Articles by Kantarjian, H. Search for Related Content PubMed PubMed Citation Articles by Faderl, S. Articles by Kantarjian, H. Related Collections Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias Stefan Faderl, Varsha Gandhi, Susan O'Brien, Peter Bonate, Jorge Cortes, Elihu Estey, Miloslav Beran, William Wierda, Guillermo Garcia-Manero, Alessandra Ferrajoli, Zeev Estrov, Francis J. Giles, Min Du, Monica Kwari, Michael Keating, William Plunkett, and Hagop Kantarjian From the Departments of Leukemia and Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and ILEX Oncology, San Antonio, TX. Clofarabine (2-chloro-2'-fluoro-deoxy-9--D-arabinofuranosyladenine) is a second-generation nucleoside analog with activity in acute leukemias. As clofarabine is a potent inhibitor of ribonucleotide reductase (RnR), we hypothesized that clofarabine will modulate ara-c triphosphate accumulation and increase the antileukemic activity of cytarabine (ara-C). We conducted a phase 1-2 study of clofarabine plus ara-C in 32 patients with relapsed acute leukemia (25 acute myeloid leukemia [AML], 2 acute lymphoblastic leukemia [ALL]), 4 high-risk myelodysplastic syndrome (MDS), and 1 blast-phase chronic myeloid leukemia (CML).1 Clofarabine was given as a 1-hour intravenous infusion for 5 days (days 2 through 6) followed 4 hours later by ara-C at 1 g/m2 per day as a 2-hour intravenous infusion for 5 days (days 1 through 5). The phase 2 dose of clofarabine was 40 mg/m2 per day for 5 days. Among all patients, 7 (22%) achieved complete remission (CR), and 5 (16%) achieved CR with incomplete platelet recovery (CRp), for an overall response rate of 38%. No responses occurred in 3 patients with ALL and CML. One patient (3%) died during induction. Adverse events were mainly less than or equal to grade 2, including transient liver test abnormalities, nausea/vomiting, diarrhea, skin rashes, mucositis, and palmoplantar erythrodysesthesias. Plasma clofarabine levels generated clofarabine triphosphate accumulation, which resulted in an increase in ara-CTP in the leukemic blasts. The combination of clofarabine with ara-C is safe and active. Cellular pharmacology data support the biochemical modulation strategy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. STYCZYNSKI, L. GIL, K. DERWICH, J. WACHOWIAK, W. BALWIERZ, W. BADOWSKA, M. KRAWCZUK-RYBAK, M. MATYSIAK, M. WIECZOREK, A. BALCERSKA, et al. Comparison of Clofarabine Activity in Childhood and Adult Acute Leukemia: Individual Tumor Response Study Anticancer Res, May 1, 2009; 29(5): 1643 - 1650. [Abstract] [Full Text] [PDF] L. Willems, F. Suarez, N. Baubion, D. Decaudin, D. Ghez, O. Hermine, B. Varet, and M.-T. Rubio High risk of cardiac dysfunction after treatment of secondary acute myeloid leukaemia to breast cancer Ann. Onc., March 1, 2009; 20(3): 597 - 599. [Full Text] [PDF] J. Laubach and A. V. Rao Current and Emerging Strategies for the Management of Acute Myeloid Leukemia in the Elderly Oncologist, October 1, 2008; 13(10): 1097 - 1108. [Abstract] [Full Text] [PDF] S. Faderl, F. Ravandi, X. Huang, G. Garcia-Manero, A. Ferrajoli, Z. Estrov, G. Borthakur, S. Verstovsek, D. A. Thomas, M. Kwari, et al. A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome Blood, September 1, 2008; 112(5): 1638 - 1645. [Abstract] [Full Text] [PDF] R. M. Stone Genetically Defined Prognostic Factors and Novel Therapeutics for AML ASCO Educational Book, January 1, 2008; 2008(1): 280 - 284. [Abstract] [Full Text] [PDF] M. E. King and J. M. Rowe Recent Developments in Acute Myelogenous Leukemia Therapy Oncologist, October 1, 2007; 12(suppl_2): 14 - 21. [Abstract] [Full Text] [PDF] J. E. Karp, R. M. Ricklis, K. Balakrishnan, J. Briel, J. Greer, S. D. Gore, B. D. Smith, M. A. McDevitt, H. Carraway, M. J. Levis, et al. A phase 1 clinical-laboratory study of clofarabine followed by cyclophosphamide for adults with refractory acute leukemias Blood, September 15, 2007; 110(6): 1762 - 1769. [Abstract] [Full Text] [PDF] J.-L. Harousseau, J. E. Lancet, J. Reiffers, B. Lowenberg, X. Thomas, F. Huguet, P. Fenaux, S. Zhang, W. Rackoff, P. De Porre, et al. A phase 2 study of the oral farnesyltransferase inhibitor tipifarnib in patients with refractory or relapsed acute myeloid leukemia Blood, June 15, 2007; 109(12): 5151 - 5156. [Abstract] [Full Text] [PDF] H. P. Erba Prognostic Factors in Elderly Patients with AML and the Implications for Treatment Hematology, January 1, 2007; 2007(1): 420 - 428. [Abstract] [Full Text] [PDF] S. Faderl, S. Verstovsek, J. Cortes, F. Ravandi, M. Beran, G. Garcia-Manero, A. Ferrajoli, Z. Estrov, S. O'Brien, C. Koller, et al. Clofarabine and cytarabine combination as induction therapy for acute myeloid leukemia (AML) in patients 50 years of age or older Blood, July 1, 2006; 108(1): 45 - 51. [Abstract] [Full Text] [PDF] E. J. Jabbour, E. Estey, and H. M. Kantarjian Adult Acute Myeloid Leukemia Mayo Clin. Proc., February 1, 2006; 81(2): 247 - 260. [Abstract] [Full Text] [PDF] C. A. Schiffer Clinical Issues in the Management of Patients with Myelodysplasia Hematology, January 1, 2006; 2006(1): 205 - 210. [Abstract] [Full Text] [PDF] M. S. Tallman New Strategies for the Treatment of Acute Myeloid Leukemia Including Antibodies and Other Novel Agents Hematology, January 1, 2005; 2005(1): 143 - 150. [Abstract] [Full Text] [PDF] E. Hellstrom-Lindberg Update on Supportive Care and New Therapies: Immunomodulatory Drugs, Growth Factors and Epigenetic-Acting Agents Hematology, January 1, 2005; 2005(1): 161 - 166. [Abstract] [Full Text] [PDF]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020