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Blood, 15 November 2006, Vol. 108, No. 10, pp. 3271-3279. Prepublished online as a Blood First Edition Paper on August 1, 2006; DOI 10.1182/blood-2006-03-009142. This Article Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2006-03-009142v1 108/10/3271    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 Garcia-Manero, G. Articles by Issa, J.-P. Search for Related Content PubMed PubMed Citation Articles by Garcia-Manero, G. Articles by Issa, J.-P. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 13, 2006 Accepted July 3, 2006 Phase I/II study of the combination of 5-aza-2’ -deoxycytidine with valproic acid in patients with leukemia Guillermo Garcia-Manero*, Hagop M Kantarjian, Blanca Sanchez-Gonzalez, Hui Yang, Gary Rosner, Srdan Verstovsek, Michael Rytting, William G. Wierda, Farhad Ravandi, Charles Koller, Lianchun Xiao, Stefan Faderl, Zeev Estrov, Jorge Cortes, Susan O'Brien, Elihu Estey, Carlos Bueso-Ramos, Jackie Fiorentino, Elias Jabbour, and Jean-Pierre Issa University of Texas M.D. Anderson Cancer Center University of Texas M. D. Anderson Cancer Center Department of Leukemia, University of Texas MD Anderson Cancer Center Department of Biostatistics, University of Texas MD Anderson Cancer Center Division of Pediatrics, University of Texas MD Anderson Cancer Center Department of Hematopathology, University of Texas MD Anderson Cancer Center * Corresponding author; email: ggarciam{at}mdanderson.org. We conducted a phase I/II study of the combination of 5-aza-2’-deoxycytidine (decitabine) and the histone deacetylase inhibitor valproic acid (VPA) in patients with advanced leukemia, including older untreated patients. Fifty-four patients were treated with a fixed dose of decitabine (15 mg/m2 IV daily x 10) administered concomitantly with escalating doses of VPA orally for 10 days. A 50 mg/kg daily dose of VPA was found to be safe. Twelve (22%) patients had objective response, including 10 complete remissions (CR; 19%), and 2 (3%) CR with incomplete platelet recovery (CRp). Among 10 elderly patients with acute myelogenous leukemia or myelodysplastic syndrome, 5 (50%) had a response (4CR, 1CRp). Induction mortality was observed in 1 (2%) patient. Major cytogenetic response was documented in 6 of 8 responders. Remission duration was 7.2 months (range 1.3 to 12.6+). Overall survival was 15.3 months (range 4.6 to 20.2+) in responders. Transient DNA hypomethylation and global histone H3 and H4 acetylation were induced, and were associated with p15 reactivation. Patients with lower pretreatment levels of p15 methylation had a significantly higher response rate. In summary, this combination of epigenetic therapy in leukemia was safe and active, and was associated with transient reversal of aberrant epigenetic marks. (ClinicalTrials.gov number, NCT00075010). CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Garcia-Manero, S. Assouline, J. Cortes, Z. Estrov, H. Kantarjian, H. Yang, W. M. Newsome, W. H. Miller Jr, C. Rousseau, A. Kalita, et al. Phase 1 study of the oral isotype specific histone deacetylase inhibitor MGCD0103 in leukemia Blood, August 15, 2008; 112(4): 981 - 989. [Abstract] [Full Text] [PDF] W. P. Vaughan and J. E. Karp The Long Road to a Cure for Acute Myelocytic Leukemia: From Intensity to Specificity J. Clin. Oncol., July 20, 2008; 26(21): 3475 - 3477. [Full Text] [PDF] B. Hackanson, K. L. Bennett, R. M. Brena, J. Jiang, R. Claus, S.-S. Chen, N. Blagitko-Dorfs, K. Maharry, S. P. Whitman, T. D. Schmittgen, et al. Epigenetic Modification of CCAAT/Enhancer Binding Protein {alpha} Expression in Acute Myeloid Leukemia Cancer Res., May 1, 2008; 68(9): 3142 - 3151. [Abstract] [Full Text] [PDF] O. H. Kramer, S. Muller, M. Buchwald, S. Reichardt, and T. Heinzel Mechanism for ubiquitylation of the leukemia fusion proteins AML1-ETO and PML-RAR{alpha} FASEB J, May 1, 2008; 22(5): 1369 - 1379. [Abstract] [Full Text] [PDF] J. Geli, N. Kiss, M. Karimi, J.-J. Lee, M. Backdahl, T. J. Ekstrom, and C. Larsson Global and Regional CpG Methylation in Pheochromocytomas and Abdominal Paragangliomas: Association to Malignant Behavior Clin. Cancer Res., May 1, 2008; 14(9): 2551 - 2559. [Abstract] [Full Text] [PDF] V. M. Klimek, S. Fircanis, P. Maslak, I. Guernah, M. Baum, N. Wu, K. Panageas, J. J. Wright, P. P. Pandolfi, and S. D. Nimer Tolerability, Pharmacodynamics, and Pharmacokinetics Studies of Depsipeptide (Romidepsin) in Patients with Acute Myelogenous Leukemia or Advanced Myelodysplastic Syndromes Clin. Cancer Res., February 1, 2008; 14(3): 826 - 832. [Abstract] [Full Text] [PDF] G. Garcia-Manero, H. Yang, C. Bueso-Ramos, A. Ferrajoli, J. Cortes, W. G. Wierda, S. Faderl, C. Koller, G. Morris, G. Rosner, et al. Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes Blood, February 1, 2008; 111(3): 1060 - 1066. 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