title: Gastrointestinal ulceration as a possible side effect of bevacizumab which may herald perforation.
abstract: Chemotherapy plus bevacizumab is currently considered as the standard 1st line treatment of advanced colorectal cancer (ACC). Whereas GI perforation is a known side effect of bevacizumab, the development of GI ulcers has not been reported. We identified 18 patients with ACC who participated in a phase III multicentre trial which included chemotherapy and bevacizumab, who developed a GI ulcer (n = 6), perforation (n = 8) or both (n = 4). The risk of developing a symptomatic GI ulcer or perforation was 1.3% and 1.6%, respectively. Central review of the histology specimens showed ulceration and/or granulation tissue with neovascularisation. The majority (89%) of events developed early during treatment. Given these observations, as well as the relationship between VEGF and mucosal injury healing, we suggest that GI ulcers may occur as a side effect of treatment with bevacizumab and may herald perforation.
authors.affiliation: Department of Medical Oncology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Tol
authors.forename: A
authors.initials: A
authors.lastname: Cats
authors.forename: L
authors.initials: L
authors.lastname: Mol
authors.forename: M
authors.initials: M
authors.lastname: Koopman
authors.forename: M M E M
authors.initials: MM
authors.lastname: Bos
authors.forename: J J M
authors.initials: JJ
authors.lastname: van der Hoeven
authors.forename: N F
authors.initials: NF
authors.lastname: Antonini
authors.forename: J H J M
authors.initials: JH
authors.lastname: van Krieken
authors.forename: C J A
authors.initials: CJ
authors.lastname: Punt
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy; D005260:Female; D006801:Humans; D007416:Intestinal Perforation / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000139:chemically induced; D010437:Peptic Ulcer / Q000139:chemically induced* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000068258:Bevacizumab