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

Cancers

Leticia Martín¹  Jesus M. Banales¹  Pedro M. Rodrigues¹  Maria J. Perugorria¹  Juan I. Arenas¹  Ioana Riaño¹  Maria Varela²  Oscar Núñez³  Beatriz Mínguez⁴  Trinidad Serrano⁵ 

[1] Department of Liver and Gastrointestinal Diseases, Clinical Research Unit, Donostia University Hospital - Biodonostia Health Research Institute, 20014 San Sebastian, Spain;Digestive Service, Hepatology Unit, Asturias Central University Hospital, The University Institute of Oncology of Asturias (IUOPA), FINBA, 33006 Oviedo, Spain;Digestive Service, Infanta Sofía University Hospital, 28703 San Sebastián de los Reyes-Madrid, Spain;Liver Unit, Department of Medicine, Hospital Universitari Vall d’Hebron, Vall d´Hebron Institut of Research (VHIR), Universitat Autònoma de Barcelona, 08035 Barcelona, Spain;Liver Unit, Lozano Blesa University Hospital - Aragon Health Research Institute, 50009 Zaragoza, Spain;

关键词: hepatocellular carcinoma;    sorafenib;    pravastatin;    randomized clinical trial;    overall survival;    time to progression;   

DOI  :  10.3390/cancers12071900

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown