{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T19:34:33Z","timestamp":1781206473218,"version":"3.54.1"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T00:00:00Z","timestamp":1594684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish \u201cMinisterio de Sanidad, Servicios sociales e Igualdad\u201d","award":["EC10-201"],"award-info":[{"award-number":["EC10-201"]}]},{"name":"Spanish Carlos III Health Institute (ISCIII) cofinanced by \u201cFondo Europeo de Desarrollo Regional\u201d (FEDER)","award":["FIS PI15\/01132, PI18\/01075 and Miguel Servet Program CON14\/00129 and CPII19\/00008"],"award-info":[{"award-number":["FIS PI15\/01132, PI18\/01075 and Miguel Servet Program CON14\/00129 and CPII19\/00008"]}]},{"name":"AMMF","award":["2019"],"award-info":[{"award-number":["2019"]}]},{"name":"Euskadi RIS3","award":["2019222054"],"award-info":[{"award-number":["2019222054"]}]},{"name":"\u201cFundaci\u00f3n Cient\u00edfica de la Asociaci\u00f3n Espa\u00f1ola Contra el C\u00e1ncer\u201d (AECC Scientific Foundation)","award":["Rare cancers grant 2017"],"award-info":[{"award-number":["Rare cancers grant 2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cancers12071900","type":"journal-article","created":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T11:03:23Z","timestamp":1594724603000},"page":"1900","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Efficacy and Safety of the Combination of Pravastatin and Sorafenib for the Treatment of Advanced Hepatocellular Carcinoma (ESTAHEP Clinical Trial)"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8410-2706","authenticated-orcid":false,"given":"Ioana","family":"Ria\u00f1o","sequence":"first","affiliation":[{"name":"Department of Liver and Gastrointestinal Diseases, Clinical Research Unit, Donostia University Hospital-Biodonostia Health Research Institute, 20014 San Sebastian, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Mart\u00edn","sequence":"additional","affiliation":[{"name":"Department of Liver and Gastrointestinal Diseases, Clinical Research Unit, Donostia University Hospital-Biodonostia Health Research Institute, 20014 San Sebastian, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Varela","sequence":"additional","affiliation":[{"name":"Digestive Service, Hepatology Unit, Asturias Central University Hospital, The University Institute of Oncology of Asturias (IUOPA), FINBA, 33006 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trinidad","family":"Serrano","sequence":"additional","affiliation":[{"name":"Liver Unit, Lozano Blesa University Hospital-Aragon Health Research Institute, 50009 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"Digestive Service, Infanta Sof\u00eda University Hospital, 28703 San Sebasti\u00e1n de los Reyes-Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7276-9666","authenticated-orcid":false,"given":"Beatriz","family":"M\u00ednguez","sequence":"additional","affiliation":[{"name":"Liver Unit, Department of Medicine, Hospital Universitari Vall d\u2019Hebron, Vall d\u00b4Hebron Institut of Research (VHIR), Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"},{"name":"Carlos III Health Institute (ISCIII), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro M.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Liver and Gastrointestinal Diseases, Clinical Research Unit, Donostia University Hospital-Biodonostia Health Research Institute, 20014 San Sebastian, Spain"},{"name":"Carlos III Health Institute (ISCIII), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Perugorria","sequence":"additional","affiliation":[{"name":"Department of Liver and Gastrointestinal Diseases, Clinical Research Unit, Donostia University Hospital-Biodonostia Health Research Institute, 20014 San Sebastian, Spain"},{"name":"Carlos III Health Institute (ISCIII), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 28220 Madrid, Spain"},{"name":"Department of Medicine, Faculty of Medicine and Nursing, University of the Basque Country, University of the Basque Country (UPV\/EHU), 48940 Lejona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus M.","family":"Banales","sequence":"additional","affiliation":[{"name":"Department of Liver and Gastrointestinal Diseases, Clinical Research Unit, Donostia University Hospital-Biodonostia Health Research Institute, 20014 San Sebastian, Spain"},{"name":"Carlos III Health Institute (ISCIII), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 28220 Madrid, Spain"},{"name":"Basque Foundation for Science, IKERBASQUE, 48013 Bilbao, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan I.","family":"Arenas","sequence":"additional","affiliation":[{"name":"Department of Liver and Gastrointestinal Diseases, Clinical Research Unit, Donostia University Hospital-Biodonostia Health Research Institute, 20014 San Sebastian, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1097\/CEJ.0000000000000428","article-title":"Worldwide incidence of hepatocellular carcinoma cases attributable to major risk factors","volume":"27","author":"Baecker","year":"2018","journal-title":"Eur. 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