title: Treatment of hepatocellular carcinoma combining sorafenib and transarterial locoregional therapy: state of the science.
abstract: The potential for increased efficacy with combined transarterial chemoembolization and sorafenib is a topic of increased interest to specialists who care for patients with unresectable hepatocellular carcinoma. There is strong scientific rationale for combination therapy: transarterial chemoembolization produces ischemia and stimulates hypoxia-inducible factor-1α, resulting in a local and systemic upregulation of vascular endothelial growth factor (VEGF), which can increase tumor angiogenesis. This upregulation can theoretically be counteracted with the multikinase inhibitor sorafenib, which is thought to act directly on platelet-derived growth factor, Raf kinase, and VEGF receptors. The potential of this approach has not yet been fully realized in clinical trials, and many unanswered questions remain. This review article discusses the state of the science of arterial locoregional therapies and sorafenib.
authors.affiliation: Department of Radiology, Columbia University, New York, NY, USA.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Weintraub
authors.forename: Riad
authors.initials: R
authors.lastname: Salem
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016461:Chemoembolization, Therapeutic / Q000009:adverse effects; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D058990:Molecular Targeted Therapy; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D000077157:Sorafenib; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib
keywords: AASLD; AE; American Association for the Study of Liver Diseases; BCLC; Barcelona Clinic Liver Cancer; CI; CR; DCR; DEB; ECOG; Eastern Cooperative Oncology Group; HCC; HCV; HFSR; HR; LRT; NCT; National Clinical Trials; OR; ORR; OS; PS; RECIST; Response Evaluation Criteria In Solid Tumors; SPACE; Sorafenib or Placebo in Combination with Transarterial Chemoembolization with Doxorubicin-Eluting Beads for Intermediate-Stage Hepatocellular Carcinoma; TTP; VEGF; adverse event; complete response; confidence interval; disease control rate; doxorubicin-eluting bead; hand–foot skin reaction; hazard ratio; hepatitis C virus; hepatocellular carcinoma; locoregional therapy; objective response rate; odds ratio; overall survival; performance status; time to progression; vascular endothelial growth factor