Effect of thalidomide in hepatocellular carcinoma: assessment with power doppler US and analysis of circulating angiogenic factors.
OBJECTIVE
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.


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 alpha-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 chi(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 alpha-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.


CONCLUSIONS
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.
Hsu
Chiun
C
Department of Oncology, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan 100.
Chen
Chiung-Nien
CN
Chen
Li-Tzong
LT
Wu
Chen-Yao
CY
Hsieh
Fon-Jou
FJ
Cheng
Ann-Lii
AL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000097:blood*; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008113:Liver Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000097:blood; D011446:Prospective Studies; D013792:Thalidomide / Q000009:adverse effects / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D018615:Ultrasonography, Doppler, Color; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D000509:alpha-Fetoproteins / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; D000509:alpha-Fetoproteins; D016222:Fibroblast Growth Factor 2; D000072483:Placenta Growth Factor; D013792:Thalidomide