Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes Export

@article{citeulike:2580725, abstract = {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 drugrelated 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. 10.1182/blood-2007-06-098061}, author = {Garcia-Manero, Guillermo and Yang, Hui and Bueso-Ramos, Carlos and Ferrajoli, Alessandra and Cortes, Jorge and Wierda, William G. and Faderl, Stefan and Koller, Charles and Morris, Gail and Rosner, Gary and Loboda, Andrey and Fantin, Valeria R. and Randolph, Sophia S. and Hardwick, James S. and Reilly, John F. and Chen, Cong and Ricker, Justin L. and Secrist, Paul J. and Richon, Victoria M. and Frankel, Stanley R. and Kantarjian, Hagop M.}, citeulike-article-id = {2580725}, citeulike-linkout-0 = {http://dx.doi.org/10.1182/blood-2007-06-098061}, citeulike-linkout-1 = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/111/3/1060}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/17962510}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=17962510}, day = {1}, doi = {10.1182/blood-2007-06-098061}, journal = {Blood}, keywords = {mds}, month = {February}, number = {3}, pages = {1060--1066}, posted-at = {2008-03-24 14:28:20}, priority = {2}, title = {Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes}, url = {http://dx.doi.org/10.1182/blood-2007-06-098061}, volume = {111}, year = {2008} }

TY - JOUR ID - citeulike:2580725 L3 - citeulike-article-id:2580725 N2 - 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 drugrelated 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. 10.1182/blood-2007-06-098061 IS - 3 JF - Blood EP - 1066 TI - Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes VL - 111 SP - 1060 KW - mds AU - Garcia-Manero, Guillermo AU - Yang, Hui AU - Bueso-Ramos, Carlos AU - Ferrajoli, Alessandra AU - Cortes, Jorge AU - Wierda, William AU - Faderl, Stefan AU - Koller, Charles AU - Morris, Gail AU - Rosner, Gary AU - Loboda, Andrey AU - Fantin, Valeria AU - Randolph, Sophia AU - Hardwick, James AU - Reilly, John AU - Chen, Cong AU - Ricker, Justin AU - Secrist, Paul AU - Richon, Victoria AU - Frankel, Stanley AU - Kantarjian, Hagop PY - 2008/02/01/ UR - http://dx.doi.org/10.1182/blood-2007-06-098061 ER -