BACKGROUND: Valproic acid (VPA) inhibits histone deacetylase activity and, synergizing with all-trans retinoic acid (ATRA), achieves differentiation induction of myeloid blast cells in vitro. METHODS: We used VPA in 58 patients with acute myeloid leukemia (AML) who were too old and/or medically unfit to receive intensive chemotherapy (32 AML secondary to myelodysplastic syndrome [MDS], 22 de novo AML, 4 AML secondary to myeloproliferative syndrome). VPA serum concentrations were 50-100 mug/mL. Thirty-one patients received VPA monotherapy. ATRA was added later in 13 patients who did not respond or who relapsed. Another 27 patients received VPA plus ATRA from the start. Median treatment duration was 93 days for VPA and 88 days for ATRA. RESULTS: The response rate was only 5% according to International Working Group (IWG) criteria for AML but was 16% when IWG response criteria for MDS were used, which capture hematologic improvement and stabilization of the disease. These endpoints, which are not necessarily correlated with diminishing blast counts, are relevant for the patients' quality of life. Among 23 patients with a peripheral blast count > 5%, 6 (26%) showed a diminishing blast count, and 5 of these had a complete peripheral blast clearance. CONCLUSIONS: Future trials should combine VPA with chemotherapy or demethylating agents. Copyright 2005 American Cancer Society.
BACKGROUND:Valproic acid (VPA) inhibits histone deacetylase activity and, synergizing with all-trans retinoic acid (ATRA), achieves differentiation induction of myeloid blast cells in vitro. METHODS: We used VPA in 58 patients with acute myeloid leukemia (AML) who were too old and/or medically unfit to receive intensive chemotherapy (32 AML secondary to myelodysplastic syndrome [MDS], 22 de novo AML, 4 AML secondary to myeloproliferative syndrome). VPA serum concentrations were 50-100 mug/mL. Thirty-one patients received VPA monotherapy. ATRA was added later in 13 patients who did not respond or who relapsed. Another 27 patients received VPA plus ATRA from the start. Median treatment duration was 93 days for VPA and 88 days for ATRA. RESULTS: The response rate was only 5% according to International Working Group (IWG) criteria for AML but was 16% when IWG response criteria for MDS were used, which capture hematologic improvement and stabilization of the disease. These endpoints, which are not necessarily correlated with diminishing blast counts, are relevant for the patients' quality of life. Among 23 patients with a peripheral blast count > 5%, 6 (26%) showed a diminishing blast count, and 5 of these had a complete peripheral blast clearance. CONCLUSIONS: Future trials should combine VPA with chemotherapy or demethylating agents. Copyright 2005 American Cancer Society.
Authors: Ivana Gojo; Anchalee Jiemjit; Jane B Trepel; Alex Sparreboom; William D Figg; Sandra Rollins; Michael L Tidwell; Jacqueline Greer; Eun Joo Chung; Min-Jung Lee; Steven D Gore; Edward A Sausville; James Zwiebel; Judith E Karp Journal: Blood Date: 2007-04-01 Impact factor: 22.113
Authors: Olatoyosi M Odenike; Serhan Alkan; Dorie Sher; John E Godwin; Dezheng Huo; Stephen J Brandt; Margaret Green; Jingping Xie; Yanming Zhang; David H Vesole; Patrick Stiff; John Wright; Richard A Larson; Wendy Stock Journal: Clin Cancer Res Date: 2008-11-01 Impact factor: 12.531