title: Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III Trial.
abstract: Anaplastic thyroid cancer (ATC) has a median survival less than 5 months and, to date, no effective therapy exists. Taxanes have recently been stated as the main drug treatment for ATC, and the histone deacetylase inhibitor valproic acid efficiently potentiates the effects of paclitaxelin vitro. Based on these data, this trial assessed the efficacy and safety of the combination of paclitaxel and valproic acid for the treatment of ATC. This was a randomized, controlled phase II/III trial, performed on 25 ATC patients across 5 centers in northwest Italy. The experimental arm received the combination of paclitaxel (80 mg/m2/weekly) and valproic acid (1,000 mg/day); the control arm received paclitaxel alone. Overall survival and disease progression, evaluated in terms of progression-free survival, were the primary outcomes. The secondary outcome was the pharmacokinetics of paclitaxel. The coadministration of valproic acid did not influence the pharmacokinetics of paclitaxel. Neither median survival nor median time to progression was statistically different in the two arms. Median survival of operated-on patients was significantly better than that of patients who were not operated on. The present trial demonstrates that the addition of valproic acid to paclitaxel has no effect on overall survival and disease progression of ATC patients. This trial is registered with EudraCT 2008-005221-11.
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Maria Graziella
authors.identifier: 0000-0002-1170-8245
authors.initials: MG
authors.lastname: Catalano
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Pugliese
authors.affiliation: Oncological Endocrinology, A.O.U. "Città della Salute e della Scienza di Torino" Hospital, Turin, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Gallo
authors.affiliation: Transition Unit for Childhood Cancer Survivors, A.O.U. "Città della Salute e della Scienza di Torino" Hospital, Turin, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Brignardello
authors.affiliation: Department of Drug Science and Technology, University of Turin, Turin, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Milla
authors.affiliation: Section of Endocrinology, Division of Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Orlandi
authors.affiliation: Endocrinology, Diabetes, and Metabolism Unit, A.O. Ordine Mauriziano di Torino, "Umberto I" Hospital, Turin, Italy.
authors.forename: Paolo Piero
authors.initials: PP
authors.lastname: Limone
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy; Oncological Endocrinology, A.O.U. "Città della Salute e della Scienza di Torino" Hospital, Turin, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Arvat
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Boccuzzi
authors.affiliation: Oncological Endocrinology, A.O.U. "Città della Salute e della Scienza di Torino" Hospital, Turin, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Piovesan