SEARCH:   Advanced

Blood, 1 January 2007, Vol. 109, No. 1, pp. 52-57. Prepublished online as a Blood First Edition Paper on August 1, 2006; DOI 10.1182/blood-2006-05-021162. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-05-021162v1 109/1/52    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 Kantarjian, H. Articles by Issa, J.-P. J. Search for Related Content PubMed PubMed Citation Articles by Kantarjian, H. Articles by Issa, J.-P. J. Related Collections Neoplasia Clinical Trials and Observations Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia Hagop Kantarjian1, Yasuhiro Oki1, Guillermo Garcia-Manero1, Xuelin Huang2, Susan O'Brien1, Jorge Cortes1, Stefan Faderl1, Carlos Bueso-Ramos3, Farhad Ravandi1, Zeev Estrov1, Alessandra Ferrajoli1, William Wierda1, Jianqin Shan1, Jan Davis1, Francis Giles1, Hussain I. Saba4, and Jean-Pierre J. Issa1 Departments of Leukemia, 1 Biostatistics, 2 and Hematopathology, 3 The University of Texas M. D. Anderson Cancer Center, Houston; and the H. Lee Moffitt Cancer Center and Research Institute, 4 Tampa, FL Epigenetic therapy with hypomethylating drugs is now the standard of care in myelodysplastic syndrome (MDS). Response rates remain low, and mechanism-based dose optimization has not been reported. We investigated the clinical and pharmacodynamic results of different dose schedules of decitabine. Adults with advanced MDS or chronic myelomonocytic leukemia (CMML) were randomized to 1 of 3 decitabine schedules: (1) 20 mg/m2 intravenously daily for 5 days; (2) 20 mg/m2 subcutaneously daily for 5 days; and (3) 10 mg/m2 intravenously daily for 10 days. Randomization followed a Bayesian adaptive design. Ninety-five patients were treated (77 with MDS, and 18 with CMML). Overall, 32 patients (34%) achieved a complete response (CR), and 69 (73%) had an objective response by the new modified International Working Group criteria. The 5-day intravenous schedule, which had the highest dose-intensity, was selected as optimal; the CR rate in that arm was 39%, compared with 21% in the 5-day subcutaneous arm and 24% in the 10-day intravenous arm (P < .05). The high dose-intensity arm was also superior at inducing hypomethylation at day 5 and at activating P15 expression at days 12 or 28 after therapy. We conclude that a low-dose, dose-intensity schedule of decitabine optimizes epigenetic modulation and clinical responses in MDS. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Preferential cytogenetic response to continuous intravenous low-dose decitabine (DAC) administration in myelodysplastic syndrome with monosomy 7 Björn Rüter, Pierre Wijermans, Rainer Claus, Regina Kunzmann, and Michael Lübbert Blood 2007 110: 1080-1082. [Full Text] [PDF] Decitabine dosage in myelodysplastic syndromes Aristoteles A. N. Giagounidis Blood 2007 110: 1082-1083. [Full Text] [PDF] Response: Decitabine response with chromosome 7 abnormality in MDS, and decitabine optimal schedule Hagop Kantarjian, Xuelin Huang, and Jean-Pierre Issa Blood 2007 110: 1083. [Full Text] [PDF] This article has been cited by other articles: M. E. Figueroa, L. Skrabanek, Y. Li, A. Jiemjit, T. E. Fandy, E. Paietta, H. Fernandez, M. S. Tallman, J. M. Greally, H. Carraway, et al. MDS and secondary AML display unique patterns and abundance of aberrant DNA methylation Blood, October 15, 2009; 114(16): 3448 - 3458. [Abstract] [Full Text] [PDF] T. E. Fandy, J. G. Herman, P. Kerns, A. Jiemjit, E. A. Sugar, S.-H. Choi, A. S. Yang, T. Aucott, T. Dauses, R. Odchimar-Reissig, et al. Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies Blood, September 24, 2009; 114(13): 2764 - 2773. [Abstract] [Full Text] [PDF] M. A. Sekeres and D. P. Steensma Defining prior therapy in myelodysplastic syndromes and criteria for relapsed and refractory disease: implications for clinical trial design and enrollment Blood, September 24, 2009; 114(13): 2575 - 2580. [Abstract] [Full Text] [PDF] D. P. Steensma, M. R. Baer, J. L. Slack, R. Buckstein, L. A. Godley, G. Garcia-Manero, M. Albitar, J. S. Larsen, S. Arora, M. T. Cullen, et al. Multicenter Study of Decitabine Administered Daily for 5 Days Every 4 Weeks to Adults With Myelodysplastic Syndromes: The Alternative Dosing for Outpatient Treatment (ADOPT) Trial J. Clin. Oncol., August 10, 2009; 27(23): 3842 - 3848. [Abstract] [Full Text] [PDF] R. M. Stone How I treat patients with myelodysplastic syndromes Blood, June 18, 2009; 113(25): 6296 - 6303. [Full Text] [PDF] J.-P. J. Issa and H. M. Kantarjian Targeting DNA Methylation Clin. Cancer Res., June 15, 2009; 15(12): 3938 - 3946. [Abstract] [Full Text] [PDF] D. J. Stewart, J.-P. Issa, R. Kurzrock, M. I. Nunez, J. Jelinek, D. Hong, Y. Oki, Z. Guo, S. Gupta, and I. I. Wistuba Decitabine Effect on Tumor Global DNA Methylation and Other Parameters in a Phase I Trial in Refractory Solid Tumors and Lymphomas Clin. Cancer Res., June 1, 2009; 15(11): 3881 - 3888. [Abstract] [Full Text] [PDF] J. Datta, K. Ghoshal, W. A. Denny, S. A. Gamage, D. G. Brooke, P. Phiasivongsa, S. Redkar, and S. T. Jacob A New Class of Quinoline-Based DNA Hypomethylating Agents Reactivates Tumor Suppressor Genes by Blocking DNA Methyltransferase 1 Activity and Inducing Its Degradation Cancer Res., May 15, 2009; 69(10): 4277 - 4285. [Abstract] [Full Text] [PDF] A. M. Vannucchi, P. Guglielmelli, and A. Tefferi Advances in Understanding and Management of Myeloproliferative Neoplasms CA Cancer J Clin, May 1, 2009; 59(3): 171 - 191. [Abstract] [Full Text] [PDF] L. Hambach, K.-W. Ling, J. Pool, Z. Aghai, E. Blokland, H. J. Tanke, J. A. Bruijn, H. Halfwerk, H. van Boven, B. Wieles, et al. Hypomethylating drugs convert HA-1-negative solid tumors into targets for stem cell-based immunotherapy Blood, March 19, 2009; 113(12): 2715 - 2722. [Abstract] [Full Text] [PDF] M. Heuser, D. B. Yap, M. Leung, T. R. de Algara, A. Tafech, S. McKinney, J. Dixon, R. Thresher, B. Colledge, M. Carlton, et al. Loss of Mll5 results in pleiotropic hematopoietic defects, reduced neutrophil immune function, and extreme sensitivity to DNA demethylation Blood, February 12, 2009; 113(7): 1432 - 1443. [Abstract] [Full Text] [PDF] E. H. Estey Treatment of acute myeloid leukemia Haematologica, January 1, 2009; 94(1): 10 - 16. [Full Text] [PDF] G. Garcia-Manero Standard-of-care Approaches for Myelodysplastic Syndromes ASCO Educational Book, January 1, 2009; 2009(1): 408 - 412. [Abstract] [Full Text] [PDF] M. A. Sekeres, J. P. Maciejewski, A. A.N. Giagounidis, K. Wride, R. Knight, A. Raza, and A. F. List Relationship of Treatment-Related Cytopenias and Response to Lenalidomide in Patients With Lower-Risk Myelodysplastic Syndromes J. Clin. Oncol., December 20, 2008; 26(36): 5943 - 5949. [Abstract] [Full Text] [PDF] A. Golenkov, G. Dudina, I. Buravtsova, O. Voronova, and M. Chukavina Clinical Efficacy of Decitabine in Patients with Myelodysplastic Syndrome (MDS) Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 5096 - 5096. [Abstract] E. Parovichnikova, A. Kokhno, I. Kaplanskaya, E. Domracheva, O. Samoylova, N. Obidina, V. Mashuk, O. Bocharnikova, T. Pospelova, and V. Savchenko A Five-Day Schedule of Decitabine May Be Effective Treatment in High Risk MDS or Relapsed AML Presenting as MDS Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 5098 - 5098. [Abstract] P. A. Link, M. R. Baer, S. R. James, D. A. Jones, and A. R. Karpf p53-Inducible Ribonucleotide Reductase (p53R2/RRM2B) Is a DNA Hypomethylation-Independent Decitabine Gene Target That Correlates with Clinical Response in Myelodysplastic Syndrome/Acute Myelogenous Leukemia Cancer Res., November 15, 2008; 68(22): 9358 - 9366. [Abstract] [Full Text] [PDF] H. Kroeger, J. Jelinek, M. R. H. Estecio, R. He, K. Kondo, W. Chung, L. Zhang, L. Shen, H. M. Kantarjian, C. E. Bueso-Ramos, et al. Aberrant CpG island methylation in acute myeloid leukemia is accentuated at relapse Blood, August 15, 2008; 112(4): 1366 - 1373. [Abstract] [Full Text] [PDF] S. D. Nimer Myelodysplastic syndromes Blood, May 15, 2008; 111(10): 4841 - 4851. [Abstract] [Full Text] [PDF] J.-P. J Issa DNA Methylation as a Therapeutic Target in Cancer Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 643 - 649. [Abstract] [Full Text] [PDF] Y. Oki, J. Jelinek, L. Shen, H. M. Kantarjian, and J.-P. J. Issa Induction of hypomethylation and molecular response after decitabine therapy in patients with chronic myelomonocytic leukemia Blood, February 15, 2008; 111(4): 2382 - 2384. [Abstract] [Full Text] [PDF] M. Schmitt, A. Schmitt, M. T. Rojewski, J. Chen, K. Giannopoulos, F. Fei, Y. Yu, M. Gotz, M. Heyduk, G. Ritter, et al. RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses Blood, February 1, 2008; 111(3): 1357 - 1365. [Abstract] [Full Text] [PDF] N. Kroger Epigenetic Modulation and Other Options to Improve Outcome of Stem Cell Transplantation in MDS Hematology, January 1, 2008; 2008(1): 60 - 67. [Abstract] [Full Text] [PDF] E. R. Plimack, D. J. Stewart, and J.-P. J. Issa Combining Epigenetic and Cytotoxic Therapy in the Treatment of Solid Tumors J. Clin. Oncol., October 10, 2007; 25(29): 4519 - 4521. [Full Text] [PDF] W. Blum, R. B. Klisovic, B. Hackanson, Z. Liu, S. Liu, H. Devine, T. Vukosavljevic, L. Huynh, G. Lozanski, C. Kefauver, et al. Phase I Study of Decitabine Alone or in Combination With Valproic Acid in Acute Myeloid Leukemia J. Clin. Oncol., September 1, 2007; 25(25): 3884 - 3891. [Abstract] [Full Text] [PDF] B. Ruter, P. Wijermans, R. Claus, R. Kunzmann, and M. Lubbert Preferential cytogenetic response to continuous intravenous low-dose decitabine (DAC) administration in myelodysplastic syndrome with monosomy 7 Blood, August 1, 2007; 110(3): 1080 - 1082. [Full Text] [PDF] A. A. N. Giagounidis Decitabine dosage in myelodysplastic syndromes Blood, August 1, 2007; 110(3): 1082 - 1083. [Full Text] [PDF] H. Kantarjian, X. Huang, and J.-P. Issa Response: Decitabine response with chromosome 7 abnormality in MDS, and decitabine optimal schedule Blood, August 1, 2007; 110(3): 1083 - 1083. [Full Text] [PDF] H. E. Carraway and S. D. Gore Addition of Histone Deacetylase Inhibitors in Combination Therapy J. Clin. Oncol., May 20, 2007; 25(15): 1955 - 1956. [Full Text] [PDF] E. Estey Acute Myeloid Leukemia and Myelodysplastic Syndromes in Older Patients J. Clin. Oncol., May 10, 2007; 25(14): 1908 - 1915. [Abstract] [Full Text] [PDF] J.-P. J. Issa DNA Methylation as a Therapeutic Target in Cancer Clin. Cancer Res., March 15, 2007; 13(6): 1634 - 1637. [Abstract] [Full Text] [PDF] G. Garcia-Manero Modifying the Epigenome as a Therapeutic Strategy in Myelodysplasia Hematology, January 1, 2007; 2007(1): 405 - 411. [Abstract] [Full Text] [PDF] A. Raza, F. Z. Raza, N. Galili, H. M. Kantarjian, Y. Oki, and J.-P. Issa Low-dose decitabine and high-risk MDS Blood, December 15, 2006; 108(13): 4291 - 4292. [Full Text] [PDF]

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