Hepatocellular carcinoma(HCC) is among the most common cancer diseases worldwide.Arterial hypervascularisation is an essential step for HCC tumorigenesis and can be targeted by transarterial chemoembolization(TACE).Th...Hepatocellular carcinoma(HCC) is among the most common cancer diseases worldwide.Arterial hypervascularisation is an essential step for HCC tumorigenesis and can be targeted by transarterial chemoembolization(TACE).This interventional method is the standard treatment for patients with intermediate stage HCC,but is also applied as "bridging" therapy for patients awaiting liver transplantation in many centers worldwide.Usually the devascularization effect induced by TACE is transient,consequently resulting in repeated cycles of TACE every 4-8 wk.Despite documented survival benefits,TACE can also induce the up-regulation of proangiogenic and growth factors,which might contribute to accelerated progression in patients with incomplete response.In 2007,sorafenib,a multi-tyrosine kinase and angiogenesis inhibitor,was approved as the first systemic treatment for advanced stage HCC.Other active targeted compounds,either inhibitors of angiogenesis and/or growth factors,are currently being investigated in numerous clinical trials.To overcome revascularisation or tumor progression under TACE treatment it seems therefore attractive to combine TACE with systemic targeted agents,which might theoretically block the effects of proangiogenic and growth factors.Over the last 12 mo,several retrospec-tive or prospective cohort studies combining TACE and sorafenib have been published.Nevertheless,robust results of the efficacy and tolerability of such combination strategies as proven by randomized,controlled trials are awaited in the next two years.展开更多
Hepatocellular carcinoma （HCC） is a lethal disease in most patients, due to its aggressive course and a lack of effective systemic therapies for advanced disease. Surgical resection and liver transplantation remain ...Hepatocellular carcinoma （HCC） is a lethal disease in most patients, due to its aggressive course and a lack of effective systemic therapies for advanced disease. Surgical resection and liver transplantation remain the only curative options for a small subset of patients. Few patients with HCC are diagnosed early enough to be eli- gible for curative treatment. Angiogenesis inhibition is a natural therapeutic target for all solid tumors, but par- ticularly for the highly vascularized HCC tumors. With the approval of the targeted agent sorafenib, there are now additional options for patients with HCC. Although sorafenib does produce some improvement in survival in HCC patients, the responses are not durable. In addi- tion, there are significant dermatologic, gastrointestinal, and metabolic toxicities, and, as importantly, there is still limited knowledge of its usefulness in special sub- populations with HCC. Other angiogenesis inhibitors are in development to treat HCC both in the first-line set- ting and for use following sorafenib failure; the furthest in development is brivanib, a dual fibroblast growth factor pathway and vascular endothelial growth factor receptor inhibitor. Additional agents with antiangiogenic properties also in phase IT and Ⅲ development for the treatment of patients with HCC include bevacizumab, ramucirumab, ABT-869, everolimus and ARQ 197.展开更多
文摘Hepatocellular carcinoma(HCC) is among the most common cancer diseases worldwide.Arterial hypervascularisation is an essential step for HCC tumorigenesis and can be targeted by transarterial chemoembolization(TACE).This interventional method is the standard treatment for patients with intermediate stage HCC,but is also applied as "bridging" therapy for patients awaiting liver transplantation in many centers worldwide.Usually the devascularization effect induced by TACE is transient,consequently resulting in repeated cycles of TACE every 4-8 wk.Despite documented survival benefits,TACE can also induce the up-regulation of proangiogenic and growth factors,which might contribute to accelerated progression in patients with incomplete response.In 2007,sorafenib,a multi-tyrosine kinase and angiogenesis inhibitor,was approved as the first systemic treatment for advanced stage HCC.Other active targeted compounds,either inhibitors of angiogenesis and/or growth factors,are currently being investigated in numerous clinical trials.To overcome revascularisation or tumor progression under TACE treatment it seems therefore attractive to combine TACE with systemic targeted agents,which might theoretically block the effects of proangiogenic and growth factors.Over the last 12 mo,several retrospec-tive or prospective cohort studies combining TACE and sorafenib have been published.Nevertheless,robust results of the efficacy and tolerability of such combination strategies as proven by randomized,controlled trials are awaited in the next two years.
文摘Hepatocellular carcinoma （HCC） is a lethal disease in most patients, due to its aggressive course and a lack of effective systemic therapies for advanced disease. Surgical resection and liver transplantation remain the only curative options for a small subset of patients. Few patients with HCC are diagnosed early enough to be eli- gible for curative treatment. Angiogenesis inhibition is a natural therapeutic target for all solid tumors, but par- ticularly for the highly vascularized HCC tumors. With the approval of the targeted agent sorafenib, there are now additional options for patients with HCC. Although sorafenib does produce some improvement in survival in HCC patients, the responses are not durable. In addi- tion, there are significant dermatologic, gastrointestinal, and metabolic toxicities, and, as importantly, there is still limited knowledge of its usefulness in special sub- populations with HCC. Other angiogenesis inhibitors are in development to treat HCC both in the first-line set- ting and for use following sorafenib failure; the furthest in development is brivanib, a dual fibroblast growth factor pathway and vascular endothelial growth factor receptor inhibitor. Additional agents with antiangiogenic properties also in phase IT and Ⅲ development for the treatment of patients with HCC include bevacizumab, ramucirumab, ABT-869, everolimus and ARQ 197.
