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International Journal of Endocrinology
Volume 2016 (2016), Article ID 2930414, 8 pages
http://dx.doi.org/10.1155/2016/2930414
Clinical Study

Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III Trial

1Department of Medical Sciences, University of Turin, Turin, Italy
2Oncological Endocrinology, A.O.U. “Città della Salute e della Scienza di Torino” Hospital, Turin, Italy
3Transition Unit for Childhood Cancer Survivors, A.O.U. “Città della Salute e della Scienza di Torino” Hospital, Turin, Italy
4Department of Drug Science and Technology, University of Turin, Turin, Italy
5Section of Endocrinology, Division of Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
6Endocrinology, Diabetes, and Metabolism Unit, A.O. Ordine Mauriziano di Torino, “Umberto I” Hospital, Turin, Italy

Received 30 June 2016; Accepted 8 September 2016

Academic Editor: Carlo Cappelli

Copyright © 2016 Maria Graziella Catalano et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 paclitaxel in 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.