title: Transarterial chemoembolization plus or minus intravenous bevacizumab in the treatment of hepatocellular cancer: a pilot study.
abstract: BACKGROUND
  Stimulation of vascular endothelial growth factor (VEGF) has been observed following transarterial chemoembolization (TACE) in hepatocellular cancer (HCC) and may contribute to tumor regrowth. This pilot study examined whether intravenous (IV) bevacizumab, a monoclonal antibody against VEGF, could inhibit neovessel formation after TACE.
  
  
  METHODS
  30 subjects with HCC undergoing TACE at a single academic institution were randomized with a computer-generated allocation in a one to one ratio to either bevacizumab at a dose of 10 mg/kg IV every 14 days beginning 1 week prior to TACE (TACE-BEV arm) or observation (TACE-O arm). Angiography was performed with TACE at day 8, and again at weeks 10 and 14. Repeat TACE was performed at week 14 if indicated. TACE-BEV subjects were allowed to continue bevacizumab beyond week 16. TACE-O subjects were allowed to cross-over to bevacizumab at week 16 in the setting of progressive disease. The main outcome measure was a comparison of neovessel formation by serial angiography. Secondary outcome measures were progression free survival (PFS) at 16 weeks, overall survival (OS), bevacizumab safety, and an analysis of VEGF levels before and after TACE with and without bevacizumab.
  
  
  RESULTS
  Among the 30 subjects enrolled, 9 of 15 randomized to the TACE-O arm and 14 of 15 randomized to the TACE-BEV arm completed all 3 angiograms. At week 14, 3 of 9 (33%) TACE-O subjects and 2 of 14 (14%) TACE-BEV subjects demonstrated neovascularity. The PFS at 16 weeks was 0.19 in the TACE-O arm and 0.79 in the TACE-BEV arm (p = 0.021). The median OS was 61 months in the TACE-O arm and 49 months in the TACE-BEV arm (p = 0.21). No life-threatening bevacizumab-related toxicities were observed. There were no substantial differences in bevacizumab pharmacokinetics compared to historical controls. Bevacizumab attenuated the increase in VEGF observed post-TACE.
  
  
  CONCLUSIONS
  IV bevacizumab was well tolerated in selected HCC subjects undergoing TACE, and appeared to diminish neovessel formation at week 14.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00049322.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Santa Monica, CA 90404-2429, USA. cbritten@mednet.ucla.edu
authors.forename: Carolyn D
authors.initials: CD
authors.lastname: Britten
authors.forename: Antoinette S
authors.initials: AS
authors.lastname: Gomes
authors.forename: Zev A
authors.initials: ZA
authors.lastname: Wainberg
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.forename: Rafael
authors.initials: R
authors.lastname: Amado
authors.forename: Yan
authors.initials: Y
authors.lastname: Xin
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Busuttil
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Slamon
authors.forename: Richard S
authors.initials: RS
authors.lastname: Finn
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000068258:Bevacizumab; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000378:metabolism / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010865:Pilot Projects; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab