Introduction:Although sorafenib is the upfront standard of care for advanced hepatocellular carcinoma (HCC), molecular predictors of efficacy have not been identified yet. In the ALICE-1 study, rs2010963 of VEGF-A and VEGF-C proved to be independent predictive factors for progression-free survival (PFS) and overall survival (OS) in multivariate analysis. The ALICE-1 study results were confirmed in the ALICE-2 study, in which VEGF and VEGFR SNPs were analyzed. In the ePHAS study we analyzed the SNPs of eNOS. In univariate analysis, patients homozygous for an eNOS haplotype (HT1: T-4b at eNOS-786/eNOS VNTR) had significantly shorter median PFS and OS than those with other haplotypes. These data were confirmed in the validation set.Methods:This nonpharmacological, interventional, prospective multicenter study aims to determine whether eNOS, HIF-1, VEGF, Ang2 and VEGFR polymorphisms play a role in predicting the objective response rate, PFS, and OS of advanced HCC patients treated with sorafenib. The study will involve 160 advanced HCC patients with Child-Pugh class A disease. The primary aim is to validate the prognostic or predictive roles of eNOS, Ang2, HIF-1, VEGF and VEGFR polymorphisms in relation to the clinical outcome (PFS) of HCC patients treated with sorafenib.Conclusions:Overall, our data may suggest that polymorphism analysis of the VEGF, VEGFR-2, HIF and eNOS genes can identify HCC patients who are more likely to benefit from sorafenib.

Multicenter prospective study of angiogenesis polymorphism validation in HCC patients treated with sorafenib. An INNOVATE study protocol / Gardini, Ac; Faloppi, L; Aprile, G; Brunetti, O; Caparello, C; Corbelli, J; Chessa, L; Bruno, D; Ercolani, G; Leonetti, A; de Stefano, G; Farella, N; Foschi, Fg; Lanzi, A; Dadduzio, V; Marisi, G; Masi, G; Negri, Fv; Pagan, F; Santini, D; Scarpi, E; Silletta, M; Silvestris, N; Tamburini, E; Tassinari, D; Vivaldi, C; Vespasiani Gentilucci, U; Zagonel, V; Calvetti, L; Cascinu, S; Frassineti, Gl; Scartozzi, M. - In: TUMORI. - ISSN 0300-8916. - 104:6(2018), pp. 476-479. [10.5301/tj.5000704]

Multicenter prospective study of angiogenesis polymorphism validation in HCC patients treated with sorafenib. An INNOVATE study protocol

Santini D;Vespasiani Gentilucci U;
2018

Abstract

Introduction:Although sorafenib is the upfront standard of care for advanced hepatocellular carcinoma (HCC), molecular predictors of efficacy have not been identified yet. In the ALICE-1 study, rs2010963 of VEGF-A and VEGF-C proved to be independent predictive factors for progression-free survival (PFS) and overall survival (OS) in multivariate analysis. The ALICE-1 study results were confirmed in the ALICE-2 study, in which VEGF and VEGFR SNPs were analyzed. In the ePHAS study we analyzed the SNPs of eNOS. In univariate analysis, patients homozygous for an eNOS haplotype (HT1: T-4b at eNOS-786/eNOS VNTR) had significantly shorter median PFS and OS than those with other haplotypes. These data were confirmed in the validation set.Methods:This nonpharmacological, interventional, prospective multicenter study aims to determine whether eNOS, HIF-1, VEGF, Ang2 and VEGFR polymorphisms play a role in predicting the objective response rate, PFS, and OS of advanced HCC patients treated with sorafenib. The study will involve 160 advanced HCC patients with Child-Pugh class A disease. The primary aim is to validate the prognostic or predictive roles of eNOS, Ang2, HIF-1, VEGF and VEGFR polymorphisms in relation to the clinical outcome (PFS) of HCC patients treated with sorafenib.Conclusions:Overall, our data may suggest that polymorphism analysis of the VEGF, VEGFR-2, HIF and eNOS genes can identify HCC patients who are more likely to benefit from sorafenib.
2018
Biomarkers; Hepatocellular carcinoma; Sorafenib
01 Pubblicazione su rivista::01a Articolo in rivista
Multicenter prospective study of angiogenesis polymorphism validation in HCC patients treated with sorafenib. An INNOVATE study protocol / Gardini, Ac; Faloppi, L; Aprile, G; Brunetti, O; Caparello, C; Corbelli, J; Chessa, L; Bruno, D; Ercolani, G; Leonetti, A; de Stefano, G; Farella, N; Foschi, Fg; Lanzi, A; Dadduzio, V; Marisi, G; Masi, G; Negri, Fv; Pagan, F; Santini, D; Scarpi, E; Silletta, M; Silvestris, N; Tamburini, E; Tassinari, D; Vivaldi, C; Vespasiani Gentilucci, U; Zagonel, V; Calvetti, L; Cascinu, S; Frassineti, Gl; Scartozzi, M. - In: TUMORI. - ISSN 0300-8916. - 104:6(2018), pp. 476-479. [10.5301/tj.5000704]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1641683
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