Modified transarterial chemoembolization with locoregional administration of sorafenib for treating hepatocellular carcinoma: feasibility, efficacy, and safety in the VX-2 rabbit liver tumor model

Diagn Interv Radiol. 2016 Jul-Aug;22(4):378-84. doi: 10.5152/dir.2016.15462.

Abstract

Purpose: We aimed to assess the feasibility, efficacy and safety of a local application of sorafenib within a conventional transarterial chemoembolization in the VX-2 tumor-bearing rabbit model.

Methods: VX-2 tumors were induced in the left liver lobe of 10 New Zealand White rabbits. After two weeks, growth was verified by contrast-enhanced computed tomography (CT). Five rabbits were treated by transarterial chemoembolization using an emulsion of sorafenib and ethiodized oil (referred to as SORATACE; n=5). Rabbits receiving oral sorafenib for two weeks (n=2) and untreated rabbits (n=3) served as controls. After two weeks, contrast-enhanced CT was performed, followed by animal necropsy.

Results: The change in tumor diameter between baseline and follow-up was significantly different in the SORATACE group compared with the other groups; tumor shrinkage was observed in the SORATACE group only (P = 0.016). In both control groups, preserved hypervascularity was seen in the follow-up CT in all but one tumor. All tumors in the SORATACE group were devascularized in the follow-up CT. Importantly, substantial parenchymal damage in nontargeted areas of the tumor-bearing liver lobe was seen in rabbits treated with SORATACE.

Conclusion: SORATACE demonstrated high efficacy in the treatment of experimental VX-2 liver tumors but was also associated with substantial liver parenchymal toxicity.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / therapy*
  • Cell Line, Tumor
  • Chemoembolization, Therapeutic / methods*
  • Drug Administration Schedule
  • Female
  • Liver Neoplasms / therapy*
  • Neoplasm Transplantation
  • Niacinamide / administration & dosage
  • Niacinamide / analogs & derivatives*
  • Niacinamide / pharmacology
  • Phenylurea Compounds / administration & dosage*
  • Phenylurea Compounds / pharmacology
  • Rabbits
  • Sorafenib
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Tumor Burden / drug effects

Substances

  • Phenylurea Compounds
  • Niacinamide
  • Sorafenib