Linifanib phase II trial in patients with advanced hepatocellular carcinoma (HCC).

Toh, Han Chong; Chen, P.; Carr, B. I.; Knox, J. J.; Gill, Sanjeev; Qian, Jia-mo; Qin, Qi-Fan; Ricker, Justin L.; Carlson, Dawn M.; Yong, Wei-Peng

doi:10.1200/jco.2010.28.15_suppl.4038

Cited by 17 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…80 Preliminary data from an open-label, multicenter phase II study of linifanib given at 0.25 mg/kg daily in patients with advanced-stage HCC showed a median time to tumor progression (TTP) of 3.7 months and overall survival of 9.7 months, with a tolerable safety profile. 81 This finding has encouraged further development of linifanib in HCC, and a phase III study comparing linifanib with sorafenib is ongoing (Table 1). …”

Section: Antiangiogenic Therapy Of Liver Cancermentioning

confidence: 99%

HCC and angiogenesis: possible targets and future directions

et al. 2011

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC), the most common primary liver tumor, is notoriously resistant to systemic therapies, and often recurs even after aggressive local therapies. HCCs rely on the formation of new blood vessels for growth, and VEGF is critical in this process. A hallmark of new vessel formation in tumors is their structural and functional abnormality. This leads to an abnormal tumor microenvironment characterized by low oxygen tension. The liver is perfused by both arterial and venous blood and the resulting abnormal microenvironment selects for more-aggressive malignancies. Anti-VEGF therapy with sorafenib was the first systemic therapy to demonstrate improved survival in patients with advanced-stage HCC. This important development in the treatment of HCC raises hope as well as critical questions on the future development of targeted agents including other antiangiogenic agents, which hold promise to further increase survival in this aggressive disease.

show abstract

Section: Antiangiogenic Therapy Of Liver Cancermentioning

confidence: 99%

HCC and angiogenesis: possible targets and future directions

et al. 2011

View full text Add to dashboard Cite

show abstract

“…This class of VEGFR inhibitors will be further discussed in ''Simultaneous inhibition of compensatory pro-angiogenic signaling: the role of the FGF signaling pathway.'' Linifanib [54], pazopanib [55] (both targeting VEGFR and PDGFR) and cediranib (AZD2171, a pan-VEGFR inhibitor) have been investigated for their efficacy and safety in advanced HCC patients in clinical trials (Table 1). Linifanib is currently compared with sorafenib in a randomized phase III trial for patients with advanced HCC.…”

Section: Other Vegfr Inhibitorsmentioning

confidence: 99%

Molecular targeted therapy for advanced hepatocellular carcinoma: current status and future perspectives

2010

View full text Add to dashboard Cite

Sorafenib, a multikinase inhibitor targeting vascular endothelial growth factor (VEGF)-mediated angiogenesis, is the first drug found to prolong survival of patients with advanced hepatocellular carcinoma (HCC). This advance has shifted the paradigm of systemic treatment for HCC toward molecular targeted therapy (MTT). However, the disease-stabilizing effect of VEGF signaling-targeted MTT normally lasts only for a few months, suggesting a rapid emergence of resistance in the majority of patients. To overcome the resistance to VEGF signaling-targeted MTT, strategies incorporating inhibition of either compensatory pro-angiogenic pathways or recruitment of bone marrow-derived circulating endothelial progenitors, as well as suppression of other oncogenic pathways, are currently being investigated. The combination of multiple molecular targeted agents or the use of multi-target agents may enhance the efficacy at the expense of increased toxicities. To facilitate the development of MTT for HCC, current methodologies for pharmacodynamic assessment, patient selection and target identification need to be improved. Patient selection according to the individual molecular signature of the tumor and correlative biomarker studies are encouraged while planning a clinical trial of novel MTT.

show abstract

“…In a Phase II open-label trial, 44 Child-Pugh A or B patients with unresectable HCC were given linifanib at 0.25 mg/kg daily and 0.25 mg/kg alternate day respectively [43]. The overall response rate was 6.8%.…”

Section: Other Anti-angiogenic Agentsmentioning

confidence: 99%