title: Phase II study of concomitant thalidomide during radiotherapy for hepatocellular carcinoma.
abstract: OBJECTIVE
  Thalidomide has been demonstrated to possess antitumor activity in patients with advanced hepatocellular carcinoma (HCC). The objective of the present study was to determine whether the combined treatment of thalidomide with radiotherapy (RT) is associated with acceptable toxicity and an improved clinical outcome in HCC patients.
  
  
  METHODS
  A total of 24 patients were enrolled to receive RT combined with thalidomide. A total dose of 50 Gy was delivered in 2-Gy fractions within 5 weeks. Thalidomide was administered 100 mg twice daily starting 3 days before RT until the development of unacceptable toxicity or disease progression. Blood samples were collected before, during, and after treatment to measure the levels of angiogenic factors and cytokines. The results of patients receiving the combined therapy were compared with those from 18 HCC patients receiving RT only.
  
  
  RESULTS
  No significant difference in the clinical parameters was noted between the two groups, except for the baseline interleukin-6 level, which was greater in the concomitant group (p = .05). The most common toxicities related to thalidomide use were skin rash (54.2%), somnolence (37.5%), and constipation (33.3%). No significant differences were seen in the response rate (55.6% vs. 58.3%, p = .48), median progression-free survival (182 ± 48.9 vs. 148 ± 6.2 days, p = .15), or median overall survival (258 ± 45.6 vs. 241 ± 38.6, p = .16) between those who received concomitant therapy and those who received RT alone. Thalidomide suppressed the serum basic fibroblast growth factor level significantly during RT (p = .03) and, to a lesser extent, the interleukin-6 and tumor necrosis factor-α levels. After adjusting for other potential prognostic factors in the multivariate analysis, only the baseline interleukin-6 level and stem cell-derived factor-1 during RT independently predicted the progression-free survival. A decreased serum stem cell-derived factor-1 level 1 month after RT completion was a significant predictor of the overall survival of HCC patients receiving RT.
  
  
  CONCLUSIONS
  Despite the acceptable toxicity, thalidomide provided no additional benefit for HCC patients undergoing RT.
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan. hjmc@nhri.org.tw
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Ch'ang
authors.forename: Chiun
authors.initials: C
authors.lastname: Hsu
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Chang
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Chang
authors.forename: Li-Tzong
authors.initials: LT
authors.lastname: Chen
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000401:mortality / Q000628:therapy*; D054377:Chemokine CXCL12 / Q000097:blood; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D003248:Constipation / Q000139:chemically induced; D018572:Disease-Free Survival; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced; D004334:Drug Administration Schedule; D003875:Drug Eruptions / Q000209:etiology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008113:Liver Neoplasms / Q000097:blood / Q000401:mortality / Q000628:therapy*; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D011879:Radiotherapy Dosage; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage* / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D015850:Interleukin-6; D008565:Membrane Proteins; C098069:PIGF protein, human; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D013792:Thalidomide