Multicenter Prospective Study of Angiogenesis Polymorphism Validation in HCC Patients Treated with Sorafenib. An INNOVATE Study Protocol

Andrea Casadei Gardini, Luca Faloppi, Giuseppe Aprile, Oronzo Brunetti, Chiara Caparello, Jody Corbelli, Luchino Chessa, Daniele Bruno, Giorgio Ercolani, Alessandro Leonetti, Giorgio de Stefano, Nunzia Farella, Francesco Giuseppe Foschi, Arianna Lanzi, Vincenzo Dadduzio, Giorgia Marisi, Gianluca Masi, Francesca V Negri, Flavia Pagan, Daniele SantiniEmanuela Scarpi, Marianna Silletta, Nicola Silvestris, Emiliano Tamburini, Davide Tassinari, Caterina Vivaldi, Umberto Vespasiani Gentilucci, Vittorina Zagonel, Lorenzo Calvetti, Stefano Cascinu, Giovanni Luca Frassineti, Mario Scartozzi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)tj5000704
JournalTumori
DOIs
Publication statusE-pub ahead of print - Dec 1 2017

Fingerprint Dive into the research topics of 'Multicenter Prospective Study of Angiogenesis Polymorphism Validation in HCC Patients Treated with Sorafenib. An INNOVATE Study Protocol'. Together they form a unique fingerprint.

  • Cite this

    Casadei Gardini, A., Faloppi, L., Aprile, G., Brunetti, O., Caparello, C., Corbelli, J., Chessa, L., Bruno, D., Ercolani, G., Leonetti, A., de Stefano, G., Farella, N., Foschi, F. G., Lanzi, A., Dadduzio, V., Marisi, G., Masi, G., Negri, F. V., Pagan, F., ... Scartozzi, M. (2017). Multicenter Prospective Study of Angiogenesis Polymorphism Validation in HCC Patients Treated with Sorafenib. An INNOVATE Study Protocol. Tumori, tj5000704. https://doi.org/10.5301/tj.5000704