Bevacizumab‐associated intestinal perforation and perioperative complications in patients receiving bevacizumab

Abstract

Aim The purposes of this study are to present cases of emergency surgery in which gastrointestinal perforation occurred during bevacizumab administration, consider the indications for emergency surgery, and examine the safety of scheduled surgery after a washout period for bevacizumab. Methods (a) We retrospectively investigated seven patients who underwent emergency surgery for bevacizumab‐associated intestinal perforation. (b) We investigated 104 patients with advanced colorectal cancer treated with neoadjuvant therapy who underwent surgery from 2008 to 2018, retrospectively. Results (a) In the seven patients undergoing emergency surgery for gastrointestinal perforation, the median bevacizumab administration and washout periods were 16 weeks and 24 days, respectively. A stoma was created in all patients except in those who were not candidates. Two patients developed postoperative abdominal abscesses, and two patients died from perioperative sepsis and gastrointestinal bleeding, respectively; both of these patients had poor performance status. (b) In patients receiving bevacizumab (n = 45) and patients treated with bevacizumab‐free regimens as neoadjuvant therapy (n = 59), 31 and 52 patients received chemoradiotherapy, respectively. We found no correlation with postoperative complications with or without bevacizumab. Conclusion The surgical indications should be considered carefully in patients with gastrointestinal perforation secondary to bevacizumab administration. Meanwhile, after appropriate cessation time, scheduled surgery following bevacizumab administration is feasible.

Interferon‐regulatory factor‐1 boosts bevacizumab cardiotoxicity by the vascular endothelial growth factor A/14‐3‐3γ axis

“…BVZ, the most commonly used VEGFA inhibitor, is an effective anti‐angiogenic agent that has been proven to delay the progression of tumours in patients 22,23 . However, BVZ treatment may lead to microvascular damage, resulting in cardiovascular disease, thromboembolic events, and gastrointestinal perforation, 24–26 suggesting that BVZ induced cardiotoxicity may also be caused by endothelial cell damage. In addition, Previous studies reported that myocardial ischaemia is a potential life‐threatening and not uncommon complication of 5‐fluorouracil or capecitabine chemotherapy.…”

Gastrointestinal perforation associated with novel antineoplastic agents: A real-world study based on the FDA Adverse Event Reporting System

“…A meta-analysis showed that there was no statistical difference in the risk of GIP between VEGFRtyrosine kinase inhibitors (TKIs) and control groups (28). However, cases of GIP caused by anti-VEGF/VEGFR agents have been continuously reported in recent years (29)(30)(31). Wang Z et al found that ramucirumab, a novel anticancer drug that belongs to the class of anti-VEGF agents, is associated with a significant increase in the risk of GIP (32).…”

Gastrointestinal perforation after bevacizumab: a multi-site, single-institution study with a focus on survival

“…For example, Badgwell and others identified 24 patients with gastrointestinal perforation following treatment with bevacizumab and reported a 30-day mortality rate of 12.5%—in contrast to the 36% mortality rate reported here [ 17 ]. Another study reported that operative management of gastrointestinal perforation after bevacizumab yielded short-term mortality in 2 of 7 patients [ 18 ]. Three factors may explain the higher mortality reported in the current study.…”