title: Incidence and management of bevacizumab-associated gastrointestinal perforations in patients with recurrent ovarian carcinoma.
abstract: OBJECTIVE
  The objective of this study was to examine the incidence and management of bevacizumab-associated gastrointestinal (GI) perforations in patients with recurrent ovarian carcinoma.
  
  
  METHODS
  We identified all patients who received bevacizumab off protocol from August 2004-August 2008. We examined their medical records for reports of confirmed GI perforation, associated clinicopathological factors, treatment, and outcomes.
  
  
  RESULTS
  Six (4%) of 160 patients with ovarian carcinoma who had been treated with bevacizumab developed GI perforations, with a median of 4 (range, 2-8) previous cytotoxic regimens. The median serum CA-125 at the start of treatment was 228 U/mL (range, 50-3106 U/mL). The median number of bevacizumab cycles prior to perforation was 10.5 (range, 2-20). The median time from the last bevacizumab dose to diagnosis of GI perforation was 13 days (range, 1-28 days). Four (67%) patients underwent an exploratory surgery. At laparotomy, one had a gastric perforation and one had an appendiceal perforation; the site of perforation could not be identified in the other 2 Two patients (33%) were managed conservatively-one with a PEG tube and the other with supportive care. The median time of death from the date of diagnosis of GI perforation was 27 days (range, 4-326 days). Only two patients-one with a gastric and the other with an appendiceal perforation-survived >65 days. The 30-day mortality rate following a bevacizumab-associated GI perforation was 50%.
  
  
  CONCLUSIONS
  Bevacizumab-associated GI perforations in patients with recurrent ovarian carcinoma occurred in 4% of our patients. The prognosis of patients diagnosed with bevacizumab-associated GI perforations in this study was poor, and treatment should be individualized.
authors.affiliation: Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Diaz
authors.forename: William P
authors.initials: WP
authors.lastname: Tew
authors.forename: Oliver
authors.initials: O
authors.lastname: Zivanovic
authors.forename: Jason
authors.initials: J
authors.lastname: Konner
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Sabbatini
authors.forename: Lisa A
authors.initials: LA
authors.lastname: dos Santos
authors.forename: Nadeem R
authors.initials: NR
authors.lastname: Abu-Rustum
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Chi
authors.forename: Carol
authors.initials: C
authors.lastname: Aghajanian
authors.forename: Richard R
authors.initials: RR
authors.lastname: Barakat
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D015994:Incidence; D007416:Intestinal Perforation / Q000139:chemically induced* / Q000628:therapy*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab