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Sorafenib in HCC

Roser Pinyol, Robert Montal, Laia Bassaganyas, Daniela Sia, Tadatoshi Takayama, Gar-Yang Chau, Vincenzo Mazzaferro, Sasan Roayaie, Han Chu Lee, Norihiro Kokudo, Zhongyang Zhang, Sara Torrecilla, Agrin Moeini, Leonardo Rodriguez-Carunchio, Edward Gane, Chris Verslype, Adina Emilia Croitoru, Umberto Cillo, Manuel de la Mata, Luigi Lupo, Simone Strasser, Joong-Won Park, Jordi Camps, Manel Solé, Swan N Thung, Augusto Villanueva, Carol Pena, Gerold Meinhardt, Jordi Bruix, Josep M Llovet
OBJECTIVE: Sorafenib is the standard systemic therapy for advanced hepatocellular carcinoma (HCC). Survival benefits of resection/local ablation for early HCC are compromised by 70% 5-year recurrence rates. The phase 3 STORM trial comparing sorafenib with placebo as adjuvant treatment did not achieve its primary endpoint of improving recurrence-free survival (RFS). The biomarker companion study BIOSTORM aims to define (A) predictors of recurrence prevention with sorafenib and (B) prognostic factors with B level of evidence...
August 14, 2018: Gut
Ronggao Chen, Qiyang Cheng, Kwabena Gyabaah Owusu-Ansah, Jun Chen, Guangyuan Song, Haiyang Xie, Lin Zhou, Xiao Xu, Donghai Jiang, Shusen Zheng
The prognosis of advanced hepatocellular carcinoma (HCC) patients remains extremely poor, partially due to the development of acquired resistance to sorafenib and chemotherapy. Cabazitaxel, a semisynthetic taxane, has been approved for the therapy of docetaxel-resistant prostate cancer. However, no studies have been performed on the effect of cabazitaxel on HCC, and whether cabazitaxel remains sensitive in chemotherapy-resistant and sorafenib-resistant HCC cells is not clear. Our results demonstrate that cabazitaxel is highly toxic to HCC cell lines in a time- and dose-dependent manner by inducing G2/M phase arrest and apoptosis in vitro...
2018: American Journal of Cancer Research
Rodolfo Sacco, Alessandro Granito, Irene Bargellini, Teresa Zolfino, Carlo Saitta, Luca Marzi, Gherardo Tapete, Giampaolo Bresci, Sara Marinelli, Francesco Tovoli, Simona Attardo, Margherita Rossi, Lucio Urbani, Santino Marchi, Piero Buccianti, Giuseppe Cabibbo
AIM: This multicenter field-practice study evaluates outcomes of long-term sorafenib in hepatocellular carcinoma (HCC) patients. METHODS: Consecutive HCC patients on sorafenib were enrolled. We evaluated those receiving sorafenib for ≥12 months. RESULTS: Out of 800 patients on sorafenib, 81 (10%) received long-term treatment. Median duration of treatment was 22.7 months (range: 12.3-92.6). Only 21 (26%) reported grade 3/4 adverse events...
August 9, 2018: Future Oncology
Sowmini Medavaram, Yue Zhang
Background: Prognosis is very poor for advanced HCC patients partially due to lack of effective systemic treatment. Sorafenib was the only approved agent for advanced HCC since 2007 until recent breakthroughs. In this article, we will review the newer approved and promising agents in the treatment of advanced HCC in the first line setting and beyond progression. Main body: The Food and Drug Administration approved sorafenib as it demonstrated 3 months overall survival benefit compared to placebo in the first line setting over 10 years ago...
2018: Experimental Hematology & Oncology
Wen-Hui Su, Yuh-Shan Jou, Jia-Hao Zhang, Chun-Ming Ho, Dar-In Tai
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related mortality because of its poor prognosis. Therefore, identifying targetable genetic mutations and mutational signatures associated with prognosis and treatment strategies are needed. Ultra-deep sequencing of 409 cancer genes using formalin-fixed paraffin-embedded tissue from 33 male patients with hepatitis B virus-associated HCC was performed to identify mutational signatures associated with the prognosis of HCC...
2018: Journal of Cancer
Shukui Qin, Eliza Kruger, Seng Chuen Tan, Shuqun Cheng, Nanya Wang, Jun Liang
Objectives: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally. In China, sorafenib and oxaliplatin plus infusional-fluorouracil/leucovorin (FOLFOX4) are approved for the systemic treatment of advanced HCC. This study compared the cost-effectiveness of these therapies from a healthcare system perspective and a patient perspectives. Methods: A Markov model was constructed using overall and progression-free survival rates and adverse event (AE) rate from two randomized controlled studies of advanced HCC patients from Asia: EACH for FOLFOX4 and ORIENTAL for sorafenib...
2018: Cost Effectiveness and Resource Allocation: C/E
Chuan Xing Wu, Xiao Qi Wang, Siu Ho Chok, Kwan Man, Simon Hing Yin Tsang, Albert Chi Yan Chan, Ka Wing Ma, Wei Xia, Tan To Cheung
Rationale: Hepatocellular carcinoma (HCC) is an aggressive malignant solid tumor wherein CDK1/PDK1/β-Catenin is activated, suggesting that inhibition of this pathway may have therapeutic potential. Methods: CDK1 overexpression and clinicopathological parameters were analyzed. HCC patient-derived xenograft (PDX) tumor models were treated with RO3306 (4 mg/kg) or sorafenib (30 mg/kg), alone or in combination. The relevant signaling of CDK1/PDK1/β-Catenin was measured by western blot. Silencing of CDK1 with shRNA and corresponding inhibitors was performed for mechanism and functional studies...
2018: Theranostics
Sandro Nuciforo, Isabel Fofana, Matthias S Matter, Tanja Blumer, Diego Calabrese, Tujana Boldanova, Salvatore Piscuoglio, Stefan Wieland, Femke Ringnalda, Gerald Schwank, Luigi M Terracciano, Charlotte K Y Ng, Markus H Heim
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the second most frequent cause of cancer-related mortality worldwide. The multikinase inhibitor sorafenib is the only treatment option for advanced HCC. Due to tumor heterogeneity, its efficacy greatly varies between patients and is limited due to adverse effects and drug resistance. Current in vitro models fail to recapitulate key features of HCCs. We report the generation of long-term organoid cultures from tumor needle biopsies of HCC patients with various etiologies and tumor stages...
July 31, 2018: Cell Reports
Dong Liu, Yifu Fan, Jun Li, Binbin Cheng, Wanfu Lin, Xiaoyan Li, Juan Du, Changquan Ling
Treatment with sorafenib remains the first‑line therapy for patients with advanced stage hepatocellular carcinoma (HCC), however, it has limited effect due to the acquired resistance of HCC. Elucidating the potential mechanism can assist in developing promising strategies to overcome this resistance. In the present study, a sorafenib‑refractory HCC cell was established from the Huh7 parental cell line, which was resistant to sorafenib mediated‑cytotoxicity in vitro. The cell inhibition rate and apoptosis of cells were determined by MTT assay and flow cytometry, respectively...
July 27, 2018: Oncology Reports
Yuxiao Yao, Shaoyang Sun, Jingjing Wang, Fei Fei, Zhaoru Dong, Ai-Wu Ke, Ruoyu He, Lei Wang, Lili Zhang, Min-Biao Ji, Qiang Li, Min Yu, Guo-Ming Shi, Jia Fan, Zhiyuan Gong, Xu Wang
There is limited understanding of the effects of major oncogenic pathways and their combinatorial actions on lipid composition and transformation during hepatic tumorigenesis. Here we report a negative correlation of Wnt/Myc activity with steatosis in human hepatocellular carcinoma (HCC) and perform in vivo functional studies using three conditional transgenic zebrafish models. Double-transgenic zebrafish larvae conditionally expressing human CTNNB1mt and zebrafish tcf7l2 or murine Myc together with krasv12 in hepatocytes led to severe hepatomegaly and significantly attenuated accumulation of lipid droplets and cell senescence triggered by krasv12 expression alone...
July 31, 2018: Cancer Research
Wen-Tsan Chang, Sheng-Nan Lu, Kung-Ming Rau, Ching-Shan Huang, King-Teh Lee
Sorafenib has been recommended as a new palliative therapy for advanced hepatocellular carcinoma (HCC). However, the clinical outcome of patients receiving sorafenib therapy varies. This study sought to identify which clinical method could be used to predict clinical outcome of sorafenib monotherapy in patients with advanced HCC. A total of 146 advanced HCC patients with Child-Pugh A liver function were enrolled from June 2011 to September 2015. Sorafenib doses ranged from 200 mg once daily to 400 mg twice daily...
July 2018: Kaohsiung Journal of Medical Sciences
Kosuke Saito, Masafumi Ikeda, Yasushi Kojima, Hiroko Hosoi, Yoshiro Saito, Shunsuke Kondo
Sorafenib is a multi-kinase inhibitor for treatment of advanced hepatocellular carcinoma (HCC). Beyond its clinical benefit against advanced HCC, the efficacy and safety of sorafenib chemotherapy are critical concerns. In this study, we addressed the lipid profiles associated with the efficacy and safety of sorafenib chemotherapy. Plasma samples from HCC patients before sorafenib chemotherapy (N = 44) were collected and subjected to lipidomic analysis. We measured the levels of 176 lipids belonging to 8 classes of phosphoglycerolipids, 2 classes of sphingolipids, 3 classes of neutral lipids, and 4 other classes of lipids...
July 30, 2018: Cancer Chemotherapy and Pharmacology
Josep M Llovet, Robert Montal, Daniela Sia, Richard S Finn
The global burden of hepatocellular carcinoma (HCC) is increasing and might soon surpass an annual incidence of 1 million cases. Genomic studies have established the landscape of molecular alterations in HCC; however, the most common mutations are not actionable, and only ~25% of tumours harbour potentially targetable drivers. Despite the fact that surveillance programmes lead to early diagnosis in 40-50% of patients, at a point when potentially curative treatments are applicable, almost half of all patients with HCC ultimately receive systemic therapies...
July 30, 2018: Nature Reviews. Clinical Oncology
Lei Liang, Ting-Hao Chen, Chao Li, Hao Xing, Jun Han, Ming-Da Wang, Han Zhang, Wan Yee Lau, Meng-Chao Wu, Feng Shen, Tian Yang
BACKGROUND: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is very poor. According to most HCC guidelines, sorafenib, transarterial chemoembolization (TACE) or other non-surgical treatments are recommended as the first-line therapy for these patients. However, selected patients with HCC and PVTT can undergo surgical resection (SR). The aim of this meta-analysis was to compare the outcomes of SR with Non-SR for such patients. METHODS: The PubMed, Embase, Medline and Cochrane library were searched for studies which compared SR with Non-SR for HCC and PVTT published before December 2017...
July 25, 2018: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
Barbara Schellhaas, Deike Strobel, Miriam Stumpf, Marion Ganslmayer, Lukas Pfeifer, Ruediger S Goertz, Markus F Neurath, Steffen Zopf
OBJECTIVES: Therapeutic approaches in the treatment of hepatocellular carcinoma (HCC) depend on tumour stage, liver function and patient comorbidities. The aim of this study was to investigate the influence of tumour stage and therapeutic approach on overall survival in HCC. MATERIALS AND METHODS: Two hundred and fourteen patients with HCC diagnosed between December 2012 and May 2017 were assessed retrospectively for tumour stage [Barcelona Clinic Liver Cancer (BCLC)], liver function (Child-Pugh score), therapeutic approach and outcome (mean survival time)...
July 26, 2018: European Journal of Gastroenterology & Hepatology
Teiji Kuzuya, Masatoshi Ishigami, Yoji Ishizu, Takashi Honda, Kazuhiko Hayashi, Tetsuya Ishikawa, Yoshiki Hirooka, Hidemi Goto
There have been some reports that a vitamin K2 (VK2) analog is beneficial for the prevention of recurrence in hepatocellular carcinoma (HCC) patients after curative therapy. However, the VK2 analogs in current use do not appear to exhibit dramatic antitumor effects when administered alone. Here, we report the case of a 67-year-old male patient with sorafenib-failure advanced HCC who achieved complete response (CR) after VK2 analog monotherapy. At the time of sorafenib-failure confirmation, the patient had multiple intrahepatic tumors, multiple lung metastases, and Vp3 portal vein tumor thrombosis...
July 27, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Tianying Zheng, Hanyu Jiang, Yi Wei, Zixing Huang, Jie Chen, Ting Duan, Bin Song
Sorafenib, which is a novel targeted agent, plays an important role in treating advanced hepatocellular carcinoma (HCC) through its antiangiogenic and antiproliferative effects. However, conventional morphology-based radiographic evaluation systems may underestimate the efficacy of sorafenib in HCC due to a lack of apparent tumor shrinkage or altered tumor morphology in many cases. This calls for the development of more accurate imaging methods for evaluating sorafenib. The introduction of tumor burden measurements based on viability and other evolving imaging approaches for assessing therapeutic effects are promising for overcoming some of the limitations of the morphology-based criteria...
June 2018: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
Jimin Dai, Kunwei Niu, Bo Wang, Yijie Li, Congcong Xia, Kaishan Tao, Jingyao Dai
Objective To explore the role of sestrin2 (SESN2) in sorafenib primary resistance and the underlying mechanism in hepatocellular carcinoma (HCC) cells. Methods Real-time quantitative PCR (qRT-PCR) and Western blot analysis were performed to examine SESN2 mRNA and protein levels in Bel-7404, SNU-398, HLE, HLF and Hep3B cell lines. Immunohistochemical staining was used to detect SESN2 expression in HCC tissues. After the treatment of 0, 2, 5, 10, 15, 20, 25 μmol/L sorafenib for 24 hours, CCK-8 assay was performed to detect the cell viability and subsequent IC50 of sorafenib in the above HCC cell lines...
May 2018: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Po-Hong Liu, Teh-Ia Huo, Rebecca A Miksad
Portal vein tumor thrombosis (PVTT) commonly occurs in patients with hepatocellular carcinoma (HCC). Patients with PVTT usually have an aggressive disease course, decreased liver function reserve, limited treatment options, higher recurrence rates after treatment, and, therefore, worse overall survival. Among untreated HCC patients with PVTT, the median overall survival has been reported as low as 2 to 4 months. Historically, many aspects of PVTT have impacted the theoretical and practical safety and efficacy of treatment, for example, disordered blood flow and associated impairment of liver function, heat-sink effects of blood flow in the area of the PVTT, and risk of recurrence due to tumor location in the blood vessel...
August 2018: Seminars in Liver Disease
Kazuhiro Saito, Joseph Ledsam, Katsutoshi Sugimoto, Steven Sourbron, Yoichi Araki, Koichi Tokuuye
Objective: Dynamic contrast-enhanced MRI (DCE-MRI) can measure the changes in tumor blood flow, vascular permeability and interstitial and intravascular volume. The objective was to evaluate the efficacy of DCE-MRI in prediction of Barcelona Clinic Liver Cancer (BCLC) staging B or C hepatocellular carcinoma (HCC) response after treatment with transcatheter arterial chemoembolization (TACE) followed by sorafenib therapy. Methods: Sorafenib was administered four days after TACE of BCLC staging B or C HCC in 11 patients (21 lesions)...
April 20, 2018: Journal of the Belgian Society of Radiology
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