Efficacy and Tolerability of Low-Dose Thalidomide as First-Line Systemic Treatment of Patients with Advanced Hepatocellular Carcinoma

Abstract

Objective: The systemic treatment of advanced hepatocellular carcinoma (HCC) has produced disappointing results thus far. HCC is a hypervascular tumor with over-expression of angiogenic factors such as vascular endothelial growth factor. Thalidomide is an anti-neoplastic agent with anti-angiogenic and other mechanisms of action. We aim to evaluate the efficacy and toxicity of low-dose (100 mg) thalidomide as the first-line treatment of advanced HCC. Methods: Between August 2003 and March 2007, 45 patients who had received thalidomide 100 mg daily as first-line treatment of advanced HCC were reviewed retrospectively. Advanced HCC was defined as either metastatic or not amenable to surgical or locoregional therapies. Diagnosis of HCC was based on clinical, biochemical and radiological grounds. Survival was analyzed by the Kaplan-Meier method. Results: Thirty-eight patients were evaluable for response and toxicity. Two (5%) patients had partial response and 8 (21%) had stable disease. The overall median survival of patients in this cohort was 3.2 months (95% CI: 2.8–3.7 months). The common toxicities were somnolence (13%), peripheral neuropathy (11%) and ankle edema (8%), with no grade 3 or 4 toxicities and treatment-related deaths. Conclusion: Our study shows that a single agent, low-dose thalidomide has a modest clinical activity with good tolerability in treating advanced HCC patients.