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Efficacy and Safety of the Combination of Pravastatin and Sorafenib for the Treatment of Advanced Hepatocellular Carcinoma (ESTAHEP Clinical Trial)

Pravastatin has demonstrated anti-tumor activity in preclinical and clinical studies. This multicentric randomized double-blind placebo-controlled phase II study (NCT01418729) investigated the efficacy and safety of sorafenib + pravastatin combination on the overall survival (OS) and time to progres...

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Autores principales: Riaño, Ioana, Martín, Leticia, Varela, Maria, Serrano, Trinidad, Núñez, Oscar, Mínguez, Beatriz, Rodrigues, Pedro M., Perugorria, Maria J., Banales, Jesus M., Arenas, Juan I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409102/
https://www.ncbi.nlm.nih.gov/pubmed/32674461
http://dx.doi.org/10.3390/cancers12071900
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author Riaño, Ioana
Martín, Leticia
Varela, Maria
Serrano, Trinidad
Núñez, Oscar
Mínguez, Beatriz
Rodrigues, Pedro M.
Perugorria, Maria J.
Banales, Jesus M.
Arenas, Juan I.
author_facet Riaño, Ioana
Martín, Leticia
Varela, Maria
Serrano, Trinidad
Núñez, Oscar
Mínguez, Beatriz
Rodrigues, Pedro M.
Perugorria, Maria J.
Banales, Jesus M.
Arenas, Juan I.
author_sort Riaño, Ioana
collection PubMed
description Pravastatin has demonstrated anti-tumor activity in preclinical and clinical studies. This multicentric randomized double-blind placebo-controlled phase II study (NCT01418729) investigated the efficacy and safety of sorafenib + pravastatin combination on the overall survival (OS) and time to progression (TTP) of patients with advanced hepatocellular carcinoma (aHCC). A total of 31 patients were randomized. Median OS did not differ between both groups (12.4 months for the sorafenib + pravastatin group vs. 11.6 months for the control group). Of note, however, the radiological TTP was higher in patients treated with sorafenib + pravastatin than in the control group (9.9 months vs. 3.2 months; p = 0.008). Considering all the study population, the presence of portal vein thrombosis (PVT) was associated with worse OS, being lower in patients with PVT compared to patients without PVT (6.3 months vs. 14.8 months; p = 0.026). Data also showed a decrease in OS in patients with vascular invasion (VI) compared to patients who did not present it (6.3 months vs. 14.8 months; p = 0.041). The group of patients without dermatological events (DE) showed lower OS (6.9 months vs. 14.5 months; p = 0.049). In conclusion, combination of sorafenib + pravastatin was safe and well-tolerated, prolonging the TTP of patients with aHCC but not improving the OS compared to sorafenib + placebo. The absence of PVT and VI and the development of DE are positive prognostic factors of sorafenib response.
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spelling pubmed-74091022020-08-26 Efficacy and Safety of the Combination of Pravastatin and Sorafenib for the Treatment of Advanced Hepatocellular Carcinoma (ESTAHEP Clinical Trial) Riaño, Ioana Martín, Leticia Varela, Maria Serrano, Trinidad Núñez, Oscar Mínguez, Beatriz Rodrigues, Pedro M. Perugorria, Maria J. Banales, Jesus M. Arenas, Juan I. Cancers (Basel) Article Pravastatin has demonstrated anti-tumor activity in preclinical and clinical studies. This multicentric randomized double-blind placebo-controlled phase II study (NCT01418729) investigated the efficacy and safety of sorafenib + pravastatin combination on the overall survival (OS) and time to progression (TTP) of patients with advanced hepatocellular carcinoma (aHCC). A total of 31 patients were randomized. Median OS did not differ between both groups (12.4 months for the sorafenib + pravastatin group vs. 11.6 months for the control group). Of note, however, the radiological TTP was higher in patients treated with sorafenib + pravastatin than in the control group (9.9 months vs. 3.2 months; p = 0.008). Considering all the study population, the presence of portal vein thrombosis (PVT) was associated with worse OS, being lower in patients with PVT compared to patients without PVT (6.3 months vs. 14.8 months; p = 0.026). Data also showed a decrease in OS in patients with vascular invasion (VI) compared to patients who did not present it (6.3 months vs. 14.8 months; p = 0.041). The group of patients without dermatological events (DE) showed lower OS (6.9 months vs. 14.5 months; p = 0.049). In conclusion, combination of sorafenib + pravastatin was safe and well-tolerated, prolonging the TTP of patients with aHCC but not improving the OS compared to sorafenib + placebo. The absence of PVT and VI and the development of DE are positive prognostic factors of sorafenib response. MDPI 2020-07-14 /pmc/articles/PMC7409102/ /pubmed/32674461 http://dx.doi.org/10.3390/cancers12071900 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Riaño, Ioana
Martín, Leticia
Varela, Maria
Serrano, Trinidad
Núñez, Oscar
Mínguez, Beatriz
Rodrigues, Pedro M.
Perugorria, Maria J.
Banales, Jesus M.
Arenas, Juan I.
Efficacy and Safety of the Combination of Pravastatin and Sorafenib for the Treatment of Advanced Hepatocellular Carcinoma (ESTAHEP Clinical Trial)
title Efficacy and Safety of the Combination of Pravastatin and Sorafenib for the Treatment of Advanced Hepatocellular Carcinoma (ESTAHEP Clinical Trial)
title_full Efficacy and Safety of the Combination of Pravastatin and Sorafenib for the Treatment of Advanced Hepatocellular Carcinoma (ESTAHEP Clinical Trial)
title_fullStr Efficacy and Safety of the Combination of Pravastatin and Sorafenib for the Treatment of Advanced Hepatocellular Carcinoma (ESTAHEP Clinical Trial)
title_full_unstemmed Efficacy and Safety of the Combination of Pravastatin and Sorafenib for the Treatment of Advanced Hepatocellular Carcinoma (ESTAHEP Clinical Trial)
title_short Efficacy and Safety of the Combination of Pravastatin and Sorafenib for the Treatment of Advanced Hepatocellular Carcinoma (ESTAHEP Clinical Trial)
title_sort efficacy and safety of the combination of pravastatin and sorafenib for the treatment of advanced hepatocellular carcinoma (estahep clinical trial)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409102/
https://www.ncbi.nlm.nih.gov/pubmed/32674461
http://dx.doi.org/10.3390/cancers12071900
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