title: Early alpha-fetoprotein response predicts treatment efficacy of antiangiogenic systemic therapy in patients with advanced hepatocellular carcinoma.
abstract: BACKGROUND
  Antiangiogenic therapy has become the most important treatment modality for patients with advanced hepatocellular carcinoma (HCC). In this study, the authors investigated levels of alpha-fetoprotein (AFP) as a potential biomarker for treatment efficacy of antiangiogenic therapy.
  
  
  METHODS
  Patients with advanced HCC who had been enrolled in 3 prospective phase 2 clinical trials that evaluated either sorafenib, bevacizumab, or thalidomide in combination with a potentially antiangiogenic, metronomic, oral 5-fluoropyrimidine as first-line systemic therapy were included. An early AFP response was defined as a decline >20% from baseline after 2 to 4 weeks of treatment. AFP response was analyzed for its association with treatment efficacy and survival outcome.
  
  
  RESULTS
  Seventy-two patients were included for early AFP response evaluation, and 12 of those patients (17%) were classified as early AFP responders. Early AFP responders, compared with nonresponders, had a significantly improved overall response rate (33% vs 8%; P=.037) and a significantly improved disease control rate (83% vs 35%; P=.002), which was defined as the percentage of patients who had an objective response plus stable disease for a minimum of 8 weeks. AFP responders, compared with nonresponders, also had longer median progression-free survival (PFS) (7.5 months vs 1.9 months; P=.001) and longer median overall survival (OS) (15.3 months vs 4.1 months; P=.019). In a multivariate analysis, AFP response remained a significant independent predictor of better PFS and OS.
  
  
  CONCLUSIONS
  The current results indicated that an early AFP response is a useful surrogate marker to predict treatment response and prognosis in patients with advanced HCC who receive antiangiogenic therapy.
authors.affiliation: Department of Oncology, National Taiwan University Hospital, and Cancer Research Center, National Taiwan University School of Medicine, Taipei, Taiwan.
authors.forename: Yu-Yun
authors.initials: YY
authors.lastname: Shao
authors.forename: Zhong-Zhe
authors.initials: ZZ
authors.lastname: Lin
authors.forename: Chiun
authors.initials: C
authors.lastname: Hsu
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Shen
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Hsu
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome; D000509:alpha-Fetoproteins / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D000509:alpha-Fetoproteins