Efficacy and Safety of the Combination of Pravastatin and Sorafenib for the Treatment of Advanced Hepatocellular Carcinoma (ESTAHEP Clinical Trial)
Open Access
- 14 July 2020
- Vol. 12 (7), 1900
- https://doi.org/10.3390/cancers12071900
Abstract
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.This publication has 36 references indexed in Scilit:
- Early dermatologic adverse events predict better outcome in HCC patients treated with sorafenibJournal of Hepatology, 2014
- Statins and the Risk of Hepatocellular Carcinoma in Patients With Hepatitis C Virus InfectionJournal of Clinical Oncology, 2013
- Statins Are Associated With a Reduced Risk of Hepatocellular Cancer: A Systematic Review and Meta-analysisGastroenterology, 2013
- Pravastatin inhibits cell proliferation and increased MAT1A expression in hepatocarcinoma cells and in vivo modelsCancer Cell International, 2012
- Statins potentiate cytostatic/cytotoxic activity of sorafenib but not sunitinib against tumor cell lines in vitroCancer Letters, 2010
- Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trialThe Lancet Oncology, 2008
- Chemoembolization Combined with Pravastatin Improves Survival in Patients with Hepatocellular CarcinomaDigestion, 2008
- Sorafenib in Advanced Hepatocellular CarcinomaThe New England Journal of Medicine, 2008
- Cell cycle arrest and apoptosis induction in hepatocellular carcinoma cells by HMG-CoA reductase inhibitors. Synergistic antiproliferative action with ligands of the peripheral benzodiazepine receptorJournal of Hepatology, 2005
- Statins Have Biphasic Effects on AngiogenesisCirculation, 2002