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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 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 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 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. Related Collections Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes Guillermo Garcia-Manero1, Hui Yang1, Carlos Bueso-Ramos1, Alessandra Ferrajoli1, Jorge Cortes1, William G. Wierda1, Stefan Faderl1, Charles Koller1, Gail Morris1, Gary Rosner1, Andrey Loboda2, Valeria R. Fantin2, Sophia S. Randolph2, James S. Hardwick2, John F. Reilly2, Cong Chen2, Justin L. Ricker2, J. Paul Secrist2, Victoria M. Richon2, Stanley R. Frankel2, and Hagop M. Kantarjian1 1 Departments of Leukemia, Hematopathology, and Biostatistics, University of Texas M. D. Anderson Cancer Center, Houston and 2 Merck, Whitehouse Station, NJ Vorinostat (suberoylanilide hydroxamic acid, SAHA) is a histone deacetylase inhibitor active clinically in cutaneous T-cell lymphoma and preclinically in leukemia. A phase 1 study was conducted to evaluate the safety and activity of oral vorinostat 100 to 300 mg twice or thrice daily for 14 days followed by 1-week 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 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; 7 patients had hematologic improvement 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: 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]

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