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Effect of Thalidomide in Hepatocellular Carcinoma: Assessment with Power Doppler US and Analysis of Circulating Angiogenic Factors¹

¹ From the Departments of Oncology (C.H., C.Y.W., A.L.C.), Surgery (C.N.C.), Internal Medicine (C.H., A.L.C.), and Obstetrics and Gynecology (F.J.H.), National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan 100; Graduate Institute of Clinical Medicine (C.H.) and Institute of Toxicology (A.L.C.), National Taiwan University College of Medicine, Taipei, Taiwan; Division of Cancer Research, National Health Research Institutes, Taipei, Taiwan (L.T.C., A.L.C.); and Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan (L.T.C.). Received February 12, 2004; revision requested April 20; revision received June 9; accepted July 21. Supported by grant NHRI-EX90-S829P from National Health Research Institutes, Taiwan, and grant 91–2314-B-002–176 from National Science Council, Taiwan. Address correspondence to A.L.C. (e-mail: andrew@ha.mc.ntu.edu.tw).

PURPOSE: To prospectively evaluate the feasibility of using power Doppler ultrasonography (US) and measurement of circulating angiogenic factors to assess the antiangiogenic effect of thalidomide in hepatocellular carcinoma.

MATERIALS AND METHODS: The Ethics Committee of the National Taiwan University Hospital approved the study, and all patients gave prior written informed consent. Evaluation of response to thalidomide treatment was based on findings at computed tomography (CT) and change in serum -fetoprotein level. Tumor vascularity index was evaluated with power Doppler US in patients with advanced hepatocellular carcinoma treated with 200–300 mg/d thalidomide. Serum levels of vascular endothelial growth factor, basic fibroblast growth factor, and placental growth factor were measured with enzyme-linked immunoassay. The ² test or Fisher exact test was used for categorical variables, and the nonparametric Mann-Whitney test was used for numeric variables. A P value of less than .05 was considered to indicate a statistically significant difference.

RESULTS: Of 47 patients enrolled in the study who had disease that was bidimensionally assessable on CT scans, 44 were assessable for tumor response. Of the 44 evaluated, five were classified as showing objective response (responders): One each showed a complete and a partial response according to World Health Organization criteria, and three had a decrease in -fetoprotein level by more than 50% and stable disease for 10.4, 5.3, or 3.5 months. The pretreatment vascularity index was significantly higher in responders (median, 7.42; range, 2.99–13.90) than in nonresponders (median, 2.15; range, 0–25.36) (P = .03). Four of five responders had a significant decrease in vascularity index with thalidomide. Serum levels of angiogenic factors did not differ significantly between responders and nonresponders.

CONCLUSION: Higher vascularity index may be associated with a better chance of response to thalidomide in patients with advanced hepatocellular carcinoma. Serum levels of circulating angiogenic factors do not appear to be clinically useful as an indicator of response.

© RSNA, 2005