title: Changes in plasma vascular endothelial growth factor at 8 weeks after sorafenib administration as predictors of survival for advanced hepatocellular carcinoma.
abstract: BACKGROUND
  A new predictive biomarker for determining prognosis in patients with hepatocellular carcinoma (HCC) who receive sorafenib is required, because achieving a reduction in tumor size with sorafenib is rare, even in patients who have a favorable prognosis. Vascular endothelial growth factor (VEGF) receptor is a sorafenib target. In the current study, the authors examined changes in plasma VEGF concentrations during sorafenib treatment and determined the clinical significance of VEGF as a prognostic indicator in patients with HCC.
  
  
  METHODS
  Plasma VEGF concentrations were serially measured in 63 patients with advanced HCC before and during sorafenib treatment. A plasma VEGF concentration that decreased >5% from the pretreatment level at 8 weeks was defined as a "VEGF decrease." An objective tumor response was determined using modified Response Evaluation Criteria in Solid Tumors 1 month after the initiation of therapy and every 3 months thereafter.
  
  
  RESULTS
  Patients who had a VEGF decrease at week 8 (n=14) had a longer median survival than those who did not have a VEGF decrease (n=49; 30.9 months vs 14.4 months; P=.038). All patients who had a VEGF decrease survived for >6 months, and the patients who had both a VEGF decrease and an α-fetoprotein response (n=6) survived during the observation period (median, 19.7 months; range, 6.5-31.0 months). In univariate analyses, a VEGF decrease, radiologic findings classified as progressive disease, and major vascular invasion were associated significantly with 1-year survival; and, in multivariate analysis, a VEGF decrease was identified as an independent factor associated significantly with survival.
  
  
  CONCLUSIONS
  A plasma VEGF concentration decrease at 8 weeks after starting sorafenib treatment may predict favorable overall survival in patients with advanced HCC.
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Asahina
authors.forename: Shuya
authors.initials: S
authors.lastname: Matsuda
authors.forename: Masaru
authors.initials: M
authors.lastname: Muraoka
authors.forename: Toru
authors.initials: T
authors.lastname: Nakata
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Nobuharu
authors.initials: N
authors.lastname: Tamaki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasui
authors.forename: Shoko
authors.initials: S
authors.lastname: Suzuki
authors.forename: Takanori
authors.initials: T
authors.lastname: Hosokawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishimura
authors.forename: Ken
authors.initials: K
authors.lastname: Ueda
authors.forename: Teiji
authors.initials: T
authors.lastname: Kuzuya
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Jun
authors.initials: J
authors.lastname: Itakura
authors.forename: Yuka
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kurosaki
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Enomoto
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; 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; D015999:Multivariate Analysis; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000077157:Sorafenib; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: C097353:AFP protein, human; D014408:Biomarkers, Tumor; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000509:alpha-Fetoproteins; D009536:Niacinamide; D000077157:Sorafenib
keywords: antiangiogenic therapy; biomarker; hepatocellular carcinoma; prognosis; α-fetoprotein