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• W2085053844 abstract "Oral valproic acid (VPA), which is a histone deacetylase inhibitor, was used in a phase II trial to treat patients with castration-resistant prostate cancer (CRPC). Ten patients with CRPC were treated with oral VPA. Oral VPA was not well tolerated in this patient population at a dose targeted to a serum level less than 50 microg/L. The main toxicities were grades 1 and 2 neurologic events and grades 1 and 2 fatigue that caused interruption in the administration of oral VPA and dose delays. Two (20%) of 10 patients had prostate-specific antigen (PSA) responses, and one response was durable. Intensive biomarker collections (weekly) revealed that PSA levels were inversely correlated with total VPA levels. Histone acetylation could not be consistently observed in peripheral lymphocytes using oral VPA. Oral VPA can be administered to CRPC patients with resultant PSA responses. However, oral VPA cannot be administered reliably to achieve consistent levels or duration to be useful in the treatment of CRPC patients. It is unlikely that PSA responses from oral VPA are related to histone deacetylase inhibition. Development of oral VPA in prostate cancers is not recommended using an oral formulation. An intensive biomarker strategy is useful to develop clinical hypotheses in patients with CRPCs in small numbers of patients." @default.
• W2085053844 created "2016-06-24" @default.
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• W2085053844 date "2008-09-01" @default.
• W2085053844 modified "2023-10-12" @default.
• W2085053844 title "A Phase II Clinical Trial of Oral Valproic Acid in Patients with Castration-Resistant Prostate Cancers Using an Intensive Biomarker Sampling Strategy" @default.
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• W2085053844 doi "https://doi.org/10.1593/tlo.08136" @default.
• W2085053844 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2533142" @default.
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