Intestinal Perforation in Colorectal Cancers Treated with Bevacizumab (Avastin®)

Abstract

Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), and it has shown promise as a clinical agent against metastatic colorectal cancer, and particularly in combination with chemotherapy. Bowel perforation is a known risk that's associated with bevacizumab use, but the etiology is unknown. Here we report on two cases of metastatic colorectal cancer in which the patients suffered from intestinal perforation after chemotherapy with bevacizumab.

Sigmoid Colon Perforation Related to Bevacizumab in a Patient With Glioblastoma

“…The exact mechanism of perforation due to anti-VEGF therapy have yet to be elucidated, but current literature suggests that VEGF actively takes place in wound healing; thus, ulcerative lesions in the GI appear to not heal properly when the VEGF angiogenic action is blocked. 4,5 Our case revealed an active chronic inflammation near the perforation area, which supports the theory that VEGF is needed for proper wound healing. In conclusion, clinicians are encouraged to use bevacizumab in the proper clinical setting but should beware of side effects especially GI perforations in patients with known chronic intestinal inflammation.…”

“…1 In patients with opioid dependence, it suppresses the craving and withdrawal symptoms associated with opioid use and also blocks the euphoric effects of subsequent opioid use. 2 Although it has several reported adverse effects such as mild euphoria and respiratory depression, rare adverse effects such as delirium, 3 withdrawal psychosis, 4 and induced auditory hallucinations have been reported after both oral 5 and epidural 6 administration. We report the first case of a patient who experienced intense psychomimetic effects similar to that of lysergic acid diethylamide (LSD) after being administered sublingual buprenorphine.…”

Complications of Targeted Drug Therapies for Solid Malignancies: Manifestations and Mechanisms

“…Proposed mechanisms for gastrointestinal perforation with bevacizumab include drug-induced alterations in the gastrointestinal microvasculature leading to local ischemia and inhibition of VEGF-mediated healing of gastrointestinal tract insults, including ulcers and diverticulitis [17]. Ongoing research is examining the association between bevacizumab-associated gastrointestinal perforation and possible risk factors, including past diverticulitis or ulcers, recent endoscopy, previous gastrointestinal surgery, gastrointestinal obstruction, presence of tumor along serosal surfaces, and varying primary malignancies.…”

Retinal vascular changes following intravitreal ranibizumab injections for neovascular AMD over a 1-year period

“…Systemic administration of anti-VEGF agents has been linked to the development of complications such as, hypertension, retinal arterial vasoconstriction, thromboembolism, haemorrhage, proteinuria, and intestinal perforation. [6][7][8][9][10] Despite local, ocular delivery in the treatment of neovascular AMD, little is known as to the potential beneficial or deleterious vasoactive effects of these compounds.…”