Comparison of the antitumor activity of thalidomide between hepatitis B (HBV)- and hepatitis C (HCV)-related hepatocellular carcinoma (HCC)

Abstract

4198 Background: Previous studies suggested that chronic HCV infection may be more angiogenic than chronic HBV infection. In this study we sought to clarify if HCV- and HBV-related HCC may respond differently to thalidomide, an anti-angiogenic agent. Methods: One hundred and twelve patients with unresectable and non-embolizable HCC who had participated in 2 prospective clinical trials using single-agent thalidomide. The starting dose of thalidomide was 200 mg per day, and was gradually escalated in 100-mg steps if no limiting toxicities developed. Patients with positive serum HBV surface antigen (HBsAg) and negative anti-HCV antibody were categorized as HBV-related HCC (B-HCC, n=61), while patients with negative HBsAg and positive anti-HCV were categorized as HCV-related HCC (C-HCC, n=33). Response to thalidomide was defined by either (1) a complete or partial response according to WHO criteria or (2) a more than 50% decrease of serum α-fetoprotein level accompanied by clinically stable or improved condition lasting for more than 8 weeks for patients with elevated α-fetoprotein level. Results: All major clinicopathological features were comparable between the 2 groups except for age (C-HCC, 67.5 ± 7.6 years; B-HCC, 53.6 ± 13.7 years, p< 0.001). Eight patients with B-HCC and 9 patients with C-HCC responded to thalidomide treatment. The total response rate to thalidomide was 13.1% (95% C.I. 4.4 to 21.8%) for B-HCC and 27.3% (95% C.I. 11.2 to 43.3%) for C-HCC (p=0.09). Patients with C-HCC appeared to have better median time to disease progression (14.1 weeks vs. 8.3 weeks, p=0.03) and overall survival (32.6 weeks vs. 21.4 weeks, p=0.08) than patients with B-HCC. In multivariate analysis, staging (CLIP score), performance status and types of viral infection were independent predictors for overall survival (p<0.01), while only types of viral infection was independent predictor for time to disease progression (p=0.027). Conclusions: There is a trend favoring better anti-tumor activity of thalidomide in patients with HCV-related HCC. Whether this result is related to angiogenesis inhibition remains to be determined. No significant financial relationships to disclose.