Thalidomide in advanced hepatocellular carcinoma as antiangiogenic treatment approach: a phase I/II trial

Eur J Gastroenterol Hepatol. 2008 Oct;20(10):1012-9. doi: 10.1097/MEG.0b013e3283036740.


Background: The high vascularity of hepatocellular carcinoma (HCC) seems to be a potential therapeutic target. We evaluated the efficacy, toxicity, and histologic response to thalidomide in advanced HCC in a single center phase I/II pilot trial.

Methods: Between September 2000 and August 2004 patients with HCC uneligible for any established therapy were enrolled in the study. The initial thalidomide dosage of 100 mg/day was escalated in 100 mg steps weekly up to 300 mg/day based on tolerability. Discontinuation and dose reduction were based on toxicity. Tumor biopsies were scheduled to assess tumor microvessel density and serum levels of angiogenic factors, vascular endothelial growth factor, basic fibroblast growth factor, and endostatin were determined.

Results: Twenty-eight patients with histologically proven HCC were entered into this study. The median maximum-tolerated dose of thalidomide was 300 mg/day. Most common toxicities were fatigue (75%), dizziness (64%), nausea (43%), and constipation (39%). Two patients had stable disease for 2.6 and 5.4 months, the remaining 26 patients had disease progression. The median overall survival was 5.1 months. Well preserved liver function was associated with longer overall survival on univariate analysis (P=0.0279). The serum concentrations of vascular endothelial growth factor and endostatin increased significantly (P=0.039 and P=0.024, respectively) after 3 months of thalidomide treatment. No clear differences were observed between the serum basic fibroblast growth factor concentrations at study entry and after 3 months (P=0.983). Microvessel density did not decrease significantly during thalidomide therapy (P=0.109).

Conclusion: Thalidomide is moderately tolerated and minimally effective in large HCC.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use*
  • Capillaries / pathology
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Endostatins / blood
  • Female
  • Fibroblast Growth Factor 2 / blood
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Pilot Projects
  • Statistics, Nonparametric
  • Survival Rate
  • Thalidomide / therapeutic use*
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / blood


  • Angiogenesis Inhibitors
  • Endostatins
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Thalidomide