Italian Study Of Validation Of Angiogenesis Polymorphisms In HCC Patients Treated With Sorafenib

Sorafenib represents the standard care for advanced hepatocellular carcinoma (HCC). However, molecular predictors of sorafenib efficacy have not yet been identified. The primary aim of the study is to validate the prognostic or predictive role of eNOS,Ang2, HIF-1, VEGF and VEGFR polymorphisms in relation to clinical outcome (progression-free survival, PFS) of HCC patients treated with sorafenib.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

1. Signed and dated informed consent.
2. Ability to understand and the willingness to sign a written informed consent document.
3. Male or Female, aged \>18 years.
4. Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less.
5. Life expectancy of 12 weeks or more.
6. Adequate hematologic function.
7. Patients were required to have at least one untreated target lesion that could be measured in one dimension, according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).
8. Concomitant antiviral systemic therapy was allowed.
9. Resolution of all acute toxic effects of any prior local treatment.
10. HCC diagnosed according to the AASLD and/or EASL criteria.

Exclusion Criteria:

1. Previous or concurrent cancer that is distinct in primary site or histology from HCC.
2. Renal failure requiring hemo- or peritoneal dialysis.
3. Presence of recent (\< 6 months) or current cardiac failure Known history of human immunodeficiency virus (HIV) infection.
4. Known central nervous system tumors including metastatic brain disease.
5. Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.
6. Any prior local therapy within 4 weeks of study entry.
7. Pregnancy or breastfeeding.

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• BACKGROUNDScartozzi M, Faloppi L, Svegliati Baroni G, Loretelli C, Piscaglia F, Iavarone M, Toniutto P, Fava G, De Minicis S, Mandolesi A, Bianconi M, Giampieri R, Granito A, Facchetti F, Bitetto D, Marinelli S, Venerandi L, Vavassori S, Gemini S, D'Errico A, Colombo M, Bolondi L, Bearzi I, Benedetti A, Cascinu S. VEGF and VEGFR genotyping in the prediction of clinical outcome for HCC patients receiving sorafenib: the ALICE-1 study. Int J Cancer. 2014 Sep 1;135(5):1247-56. doi: 10.1002/ijc.28772. Epub 2014 Feb 20. PMID 24510746
• DERIVEDCasadei-Gardini A, Marisi G, Dadduzio V, Gramantieri L, Faloppi L, Ulivi P, Foschi FG, Tamburini E, Vivaldi C, Rizzato MD, Ielasi L, Canale M, Conti F, Rudnas B, Fornaro L, Silvestris N, Silletta M, Cardellino GG, Lonardi S, Fornari F, Orsi G, Rovesti G, Zagonel V, Cascinu S, Scartozzi M. Association of NOS3 and ANGPT2 Gene Polymorphisms with Survival in Patients with Hepatocellular Carcinoma Receiving Sorafenib: Results of the Multicenter Prospective INNOVATE Study. Clin Cancer Res. 2020 Sep 1;26(17):4485-4493. doi: 10.1158/1078-0432.CCR-19-3897. Epub 2020 May 5. PMID 32371540