Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III Trial
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. Ba...
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doaj-0bde3e5fd89c4fcca59729ef2d717f312020-11-24T23:55:58ZengHindawi LimitedInternational Journal of Endocrinology1687-83371687-83452016-01-01201610.1155/2016/29304142930414Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III TrialMaria Graziella Catalano0Mariateresa Pugliese1Marco Gallo2Enrico Brignardello3Paola Milla4Fabio Orlandi5Paolo Piero Limone6Emanuela Arvat7Giuseppe Boccuzzi8Alessandro Piovesan9Department of Medical Sciences, University of Turin, Turin, ItalyDepartment of Medical Sciences, University of Turin, Turin, ItalyOncological Endocrinology, A.O.U. “Città della Salute e della Scienza di Torino” Hospital, Turin, ItalyTransition Unit for Childhood Cancer Survivors, A.O.U. “Città della Salute e della Scienza di Torino” Hospital, Turin, ItalyDepartment of Drug Science and Technology, University of Turin, Turin, ItalySection of Endocrinology, Division of Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, Turin, ItalyEndocrinology, Diabetes, and Metabolism Unit, A.O. Ordine Mauriziano di Torino, “Umberto I” Hospital, Turin, ItalyDepartment of Medical Sciences, University of Turin, Turin, ItalyDepartment of Medical Sciences, University of Turin, Turin, ItalyOncological Endocrinology, A.O.U. “Città della Salute e della Scienza di Torino” Hospital, Turin, ItalyAnaplastic 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.http://dx.doi.org/10.1155/2016/2930414 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maria Graziella Catalano Mariateresa Pugliese Marco Gallo Enrico Brignardello Paola Milla Fabio Orlandi Paolo Piero Limone Emanuela Arvat Giuseppe Boccuzzi Alessandro Piovesan |
spellingShingle |
Maria Graziella Catalano Mariateresa Pugliese Marco Gallo Enrico Brignardello Paola Milla Fabio Orlandi Paolo Piero Limone Emanuela Arvat Giuseppe Boccuzzi Alessandro Piovesan Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III Trial International Journal of Endocrinology |
author_facet |
Maria Graziella Catalano Mariateresa Pugliese Marco Gallo Enrico Brignardello Paola Milla Fabio Orlandi Paolo Piero Limone Emanuela Arvat Giuseppe Boccuzzi Alessandro Piovesan |
author_sort |
Maria Graziella Catalano |
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 |
title_short |
Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III Trial |
title_full |
Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III Trial |
title_fullStr |
Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III Trial |
title_full_unstemmed |
Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III Trial |
title_sort |
valproic acid, a histone deacetylase inhibitor, in combination with paclitaxel for anaplastic thyroid cancer: results of a multicenter randomized controlled phase ii/iii trial |
publisher |
Hindawi Limited |
series |
International Journal of Endocrinology |
issn |
1687-8337 1687-8345 |
publishDate |
2016-01-01 |
description |
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. |
url |
http://dx.doi.org/10.1155/2016/2930414 |
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