Adjuvant adenovirus-mediated delivery of herpes simplex virus thymidine kinase administration improves outcome of liver transplantation in patients with advanced hepatocellular carcinoma

Clin Cancer Res. 2007 Oct 1;13(19):5847-54. doi: 10.1158/1078-0432.CCR-07-0499.

Abstract

Purpose: Previous poor results of liver transplantation (LT) have been confirmed in patients with advanced hepatocellular carcinoma (HCC). Adenovirus-mediated delivery of herpes simplex virus thymidine kinase (ADV-TK) therapy is an established adjuvant treatment in cancer, and we evaluated its potential as an adjuvant treatment for HCC patients who underwent LT.

Experimental design: Forty-five HCC patients with tumors >5 cm in diameter participated in the study over a follow-up period of 50 months. Among these patients, 22 received LT only, and 23 received LT combined with ADV-TK therapy. All HCC patients enrolled in this study had tumors >5 cm in diameter and no metastasis in lungs or bones was detected by computed tomography or magnetic resonance imaging scans.

Results: The recurrence-free survival and the overall survival in the LT plus ADV-TK therapy group were 43.5% and 69.6%, respectively, at 3 years; both values were significantly higher than those in the LT-only group (9.1% and 19.9%, respectively). In the nonvascular invasion subgroup, overall survival was 100% and recurrence-free survival was 83.3% in the patients receiving LT plus ADV-TK, significantly higher than the patients receiving LT only.

Conclusions: HCC patients with no vascular invasion could be selected for LT followed by adjuvant ADV-TK therapy, regardless of intrahepatic huge or diffuse tumor. We propose that the current criteria for LT based on tumor size may be expanded if accompanied by ADV-TK therapy due to improved prognosis.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Adult
  • Aged
  • Carcinoma, Hepatocellular / genetics*
  • Female
  • Follow-Up Studies
  • Gene Transfer Techniques*
  • Genetic Therapy / methods*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Transplantation / methods*
  • Male
  • Middle Aged
  • Simplexvirus / enzymology*
  • Thymidine Kinase / genetics*
  • Tomography, X-Ray Computed / methods
  • Treatment Outcome

Substances

  • Thymidine Kinase