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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1060-1066. Prepublished online as a Blood First Edition Paper on October 25, 2007; DOI 10.1182/blood-2007-06-098061. This Article Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2007-06-098061v1 111/3/1060    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 Kantarjian, H. M Search for Related Content PubMed PubMed Citation Articles by Garcia-Manero, G. Articles by Kantarjian, H. M Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 26, 2007 Accepted October 10, 2007 Phase I study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) in patients with advanced leukemias and myelodysplastic syndromes Guillermo Garcia-Manero*, Hui Yang, Carlos Bueso-Ramos, Alessandra Ferrajoli, Jorge Cortes, William G. Wierda, Stefan Faderl, Charles Koller, Gail Morris, Gary Rosner, Andrey Loboda, Valeria R Fantin, Sophia S Randolph, James S Hardwick, John F Reilly, Cong Chen, Justin L Ricker, J. Paul Secrist, Victoria M Richon, Stanley R Frankel, and Hagop M Kantarjian Departments of Leukemia, Hematopathology & Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, TX, United States Merck & Co., Inc., Whitehouse Station, NJ, United States * Corresponding author; email: ggarciam{at}mdanderson.org. Vorinostat (suberoylanilide hydroxamic acid, SAHA) is a histone deacetylase inhibitor active clinically in cutaneous T-cell lymphoma and preclinically in leukemia. A phase I study was conducted to evaluate the safety and activity of oral vorinostat 100-300 mg administered twice- or thrice-daily for 14 days followed by 1-week of rest. Patients with relapsed or refractory leukemias or myelodysplastic syndromes (MDS) and untreated patients who were not candidates for chemotherapy were eligible. Of 41 patients, 31 had acute myeloid leukemia (AML), 4 chronic lymphocytic leukemia, 3 MDS, 2 acute lymphoblastic leukemia, and 1 chronic myelocytic leukemia. The maximum tolerated dose (MTD) was 200 mg twice-daily or 250 mg thrice-daily. Dose-limiting toxicities were fatigue, nausea, vomiting, and diarrhea. Common drug-related adverse experiences (>50%) were diarrhea, nausea, fatigue, and anorexia, and were mild/moderate in severity. Grade 3/4 drug-related adverse experiences included fatigue (27%), thrombocytopenia (12%), and diarrhea (10%). There were no drug-related deaths. Seven patients had hematologic improvement or response, including 2 complete responses and 2 complete responses with incomplete blood count recovery (all with AML treated at/below MTD). Increased histone acetylation was observed at all doses. Antioxidant gene expression may confer vorinostat resistance. Further evaluation of vorinostat in AML/MDS is warranted. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. N. Munster, E. H. Rubin, S. Van Belle, E. Friedman, J. K. Patterson, K. Van Dyck, X. Li, W. Comisar, J. A. Chodakewitz, J. A. Wagner, et al. A Single Supratherapeutic Dose of Vorinostat Does Not Prolong the QTc Interval in Patients with Advanced Cancer Clin. Cancer Res., November 15, 2009; 15(22): 7077 - 7084. [Abstract] [Full Text] [PDF] A. A. 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