Review article: Overview of medical treatments in unresectable hepatocellular carcinoma--an impossible meta-analysis?

Aliment Pharmacol Ther. 1998 Feb;12(2):111-26. doi: 10.1046/j.1365-2036.1998.00286.x.


Background: Controversies surrounding medical treatment in patients with unresectable hepatocellular carcinoma continue to persist.

Aim: To perform a meta-analysis of therapeutic modalities which had been evaluated in two or more randomized trials.

Methods: Fifty-two randomized trials were studied; only 30 were included. This overview identified seven therapeutic modalities which had been evaluated in two or more trials: adriamycin, 5-fluorouracil, interferon, percutaneous ethanol injection, transarterial chemotherapy, the combination of lipiodol with transarterial chemotherapy, and tamoxifen.

Results: Comparisons of survival between control groups showed substantial heterogeneity. There was no survival benefit at 1 year with adriamycin (mean difference 4%), 5-fluorouracil (mean difference -3%), percutaneous ethanol injection (mean difference 6%) or transarterial chemotherapy (mean difference -2%). For interferon, the survival benefit was significant with the Der Simonian & Laird method (mean difference 9%, 95% CI = 1-18%, P = 0.04) but not with the Peto et al. method (2.4 mean odds ratio, 95% CI = 0.9-6.8). The meta-analysis of tamoxifen showed a borderline survival benefit (mean difference 25%, 95% CI = 0-49%, P = 0.05). However, in sensitivity analyses, the survival benefit of tamoxifen was no longer significant.

Conclusions: No treatment has clearly proven efficacy in survival. 5-Fluorouracil, adriamycin and transarterial chemotherapy were not associated with survival benefit at 1 year. The number of randomized controlled trials was insufficient to enable a conclusion to be reached for interferon and percutaneous ethanol injection. Controversy persists concerning tamoxifen efficacy. Interferon and tamoxifen require new randomized controlled trials on a larger population of patients.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / therapy
  • Doxorubicin / therapeutic use
  • Ethanol / therapeutic use
  • Fluorouracil / therapeutic use
  • Humans
  • Interferons / therapeutic use
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / therapy
  • Odds Ratio
  • Randomized Controlled Trials as Topic
  • Survival Analysis
  • Tamoxifen / therapeutic use


  • Antineoplastic Agents
  • Tamoxifen
  • Ethanol
  • Doxorubicin
  • Interferons
  • Fluorouracil