title: Neoadjuvant bevacizumab persistently inactivates VEGF at the time of surgery despite preoperative cessation.
abstract: BACKGROUND
  When anti-VEGF (vascular endothelial growth factor) antibody bevacizumab is applied in neoadjuvant treatment of colorectal cancer patients with liver metastasis, 5-6 weeks between last bevacizumab dose and liver resection are currently recommended to avoid complications in wound and liver regeneration. In this context, we aimed to determine whether VEGF is inactivated by bevacizumab at the time of surgery.
  
  
  METHODS
  Fifty colorectal cancer patients with liver metastases received neoadjuvant chemotherapy ± bevacizumab supplementation. The last dose of bevacizumab was administered 6 weeks before surgery. Plasma, subcutaneous and intraabdominal wound fluid were analysed for VEGF content before and after liver resection (day 1-3). Immunoprecipitation was applied to determine the amount of bevacizumab-bound VEGF.
  
  
  RESULTS
  Bevacizumab-treated individuals showed no increase in perioperative complications. During the entire monitoring period, plasma VEGF was inactivated by bevacizumab. In wound fluid, VEGF was also completely bound by bevacizumab and was remarkably low compared with the control chemotherapy group.
  
  
  CONCLUSIONS
  These data document that following a cessation time of 6 weeks, bevacizumab is fully active and blocks circulating and local VEGF at the time of liver resection. However, despite effective VEGF inactivation no increase in perioperative morbidity is recorded suggesting that VEGF activity is not essential in the immediate postoperative recovery period.
authors: Department of Surgery, Medical University of Vienna, General Hospital, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors: P
authors: P
authors: Starlinger
authors: L
authors: L
authors: Alidzanovic
authors: D
authors: D
authors: Schauer
authors: T
authors: T
authors: Maier
authors: C
authors: C
authors: Nemeth
authors: B
authors: B
authors: Perisanidis
authors: D
authors: D
authors: Tamandl
authors: B
authors: B
authors: Gruenberger
authors: T
authors: T
authors: Gruenberger
authors: C
authors: C
authors: Brostjan
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000473:pathology*; D004334:Drug Administration Schedule; D005260:Female; D006498:Hepatectomy / Q000009:adverse effects; D006801:Humans; D047468:Immunoprecipitation; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D011183:Postoperative Complications / Q000209:etiology / Q000517:prevention & control; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab