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%. Conclusion 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.