Gastrointestinal ulceration as a possible side effect of bevacizumab which may herald perforation.
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.
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Department of Medical Oncology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
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Koopman
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van der Hoeven
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Antonini
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van Krieken
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Punt
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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
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000068258:Bevacizumab