Journal ArticleDOI
Safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma: an open-label, multicentre, phase II study
Sandrine Faivre,Eric Raymond,Eveline Boucher,Jean Douillard,Ho Y. Lim,Jun S Kim,Magaly Zappa,Silvana Lanzalone,Xun Lin,Samuel E. DePrimo,Charles S. Harmon,Ana Ruiz-Garcia,Maria Jose Lechuga,Ann-Lii Cheng +13 more
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Sunitinib showed pronounced toxicities at a dose of 50 mg/day in patients with unresectable HCC and the response rate was low, and the study did not meet the primary endpoint based on RECIST criteria.Abstract:
Summary Background Hepatocellular carcinoma (HCC) tumour spread is partly dependent on neoangiogenesis. In this open-label, multicentre, phase II trial done in Europe and Asia, sunitinib, a multitargeted tyrosine-kinase inhibitor with anti-angiogenic properties, was assessed in patients with advanced unresectable HCC. Methods Between February and July, 2006, eligible patients were enrolled and treated with repeated cycles of oral sunitinib (50 mg/day for 4 weeks, followed by 2 weeks off treatment). The primary endpoint of this Simon two-stage phase II trial was objective response rate according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria, with an expected response rate of 15%. This trial is registered with ClinicalTrials.gov, number NCT00247676. Findings Of 37 patients enrolled, one (2·7%) patient experienced a confirmed partial response, giving an overall objective response rate of 2·7% (95% CI 0·1–14·2); on the basis of this, the trial did not proceed to the second stage. 13 (35%) of 37 patients achieved stable disease for over 3 months. Commonly observed grade 3 and 4 adverse events included thrombocytopenia (14 of 37; 37·8%), neutropenia (nine of 37; 24·3%), asthenia (five of 37; 13·5%), hand–foot syndrome (four of 37; 10·8%), and anaemia (four of 37; 10·8%). There were four deaths among the 37 patients (10·8%) that were possibly related to treatment. Interpretation Sunitinib showed pronounced toxicities at a dose of 50 mg/day in patients with unresectable HCC. The response rate was low, and the study did not meet the primary endpoint based on RECIST criteria. Funding Pfizer Oncology.read more
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EASL-EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma European Association for the Study of the Liver ⇑ , European Organisation for Research and Treatment of Cancer
Josep M. Llovet,Michel Ducreux,Riccardo Lencioni,Adrian M. Di Bisceglie,Jean-Francois J. DuFour,Tim F. Greten,Eric Raymond,Tania Roskams,Vincenzo Mazzaferro,Jordi Bruix,Massimo Colombo,Andrew X. Zhu +11 more
TL;DR: The purpose of this document is to assist physicians, patients, health-care providers, and health-policy makers from Europe and worldwide in the decision-making process according to evidencebased data.
Journal ArticleDOI
Evidence-Based Diagnosis, Staging, and Treatment of Patients With Hepatocellular Carcinoma.
TL;DR: Studies now aim to identify molecular markers and imaging techniques that can detect patients with HCC at earlier stages and better predict their survival time and response to treatment.
Journal ArticleDOI
The role of signaling pathways in the development and treatment of hepatocellular carcinoma.
TL;DR: The role of the RAF/MEK/ERK pathway, phosphatidylinositol-3 kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, WNT/β-catenin pathway, insulin-like growth factor pathway, hepatocyte growth factor/c-MET pathway and growth factor-regulated angiogenic signaling are explored.
Journal ArticleDOI
Sunitinib Versus Sorafenib in Advanced Hepatocellular Cancer: Results of a Randomized Phase III Trial
Ann-Lii Cheng,Yoon-Koo Kang,Deng Yn Lin,Joong-Won Park,Masatoshi Kudo,Shukui Qin,Hyun Cheol Chung,Xiangqun Song,Jianming Xu,Guido Poggi,Masao Omata,Susan Pitman Lowenthal,Silvana Lanzalone,Liqiang Yang,Maria Jose Lechuga,Eric Raymond +15 more
TL;DR: OS with sunitinib was not superior or equivalent but was significantly inferior to sorafenib, and OS was comparable in Asian and hepatitis B-infected patients.
Journal ArticleDOI
Advances in targeted therapies for hepatocellular carcinoma in the genomic era
TL;DR: The authors summarize the molecular concepts of progression, discuss the potential reasons for clinical trial failure and propose new concepts of drug development, which might lead to clinical implementation of emerging targeted agents.
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Journal ArticleDOI
Sorafenib in Advanced Hepatocellular Carcinoma
Josep M. Llovet,Sergio Ricci,Vincenzo Mazzaferro,Philip Hilgard,Edward Gane,Jean-Frédéric Blanc,André Cosme de Oliveira,Armando Santoro,Jean-Luc Raoul,Alejandro Forner,Myron Schwartz,Camillo Porta,Stefan Zeuzem,Luigi Bolondi,Tim F. Greten,Peter R. Galle,Jean Francois Seitz,Ivan Borbath,Dieter Häussinger,Tom Giannaris,Minghua Shan,M. Moscovici,D. Voliotis,Jordi Bruix +23 more
TL;DR: In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo.
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Sorafenib in Advanced Hepatocellular Carcinoma
Josep M. Llovet,Sergio Ricci,Vincenzo Mazzaferro,Philip Hilgard,Edward Gane,Jean-Frédéric Blanc,André Cosme de Oliveira,Armando Santoro,Jean-Luc Raoul,Alejandro Forner,Myron Schwartz,Camillo Porta,Stefan Zeuzem,Luigi Bolondi,Tim F. Greten,Peter R. Galle,Jean Francois Seitz,Ivan Borbath,Dieter Häussinger,Tom Giannaris,Minghua Shan,M. Moscovici,D. Voliotis,Jordi Bruix +23 more