Gastrointestinal Perforation in Patients with Metastatic Colorectal Cancer treated with Bevacizumab (Avastin) Three Cases Report

approved by the U.S. Food and Drug Administration in February 2004 and the European Medicines Agency in January 2005 for use in metastatic colorectal cancer (mCRC). In a phase III clinical trial it was shown to improve survival and progression-free survival and an increased response rate as compared to a chemotherapy (IFL) regimen containing bolus fluorouracil (5-FU), leucovorin (LV), and irinotecan (CPT-11). Bevacizumab inhibits tumor angiogenesis, an important process in tumor growth and the formation of metastases. Inhibition of VEGF not only suppresses the growth of new blood supplying vessels of the tumor, but leads to “normalization” of existing tumor vessels, thereby reducing interstitial fluid pressure and enhancing the efficacy of chemotherapeutic drugs. Avastin is the first anti-angiogenesis drug used in colorectal cancer, which in contrast to conventional treatment with 5-FU, CPT-11, and oxaliplatin, does not have serious myelotoxicity or neurotoxicity. The reported side effects of Avastin include hypertension, proteinuria, thromboembolic events, delayed wound healing, gastrointestinal bleeding and bowel perforation. Gastrointestinal perforation associated with bevacizumab has been defined as the finding of intraperitoneal air with or without gastrointestinal or enterocutaneous fistula. Morbidity and mortality from GI perforation of using Avastin are high, and therefore clinically it is important to recognize it early. Though being with a reported rate lower than 2%, Avastin-associated bowel perforation has been found potentially fatal. Reported herein are three cases of J Soc Colon Rectal Surgeon (Taiwan) June 2011