Case reportBowel Perforation from Bevacizumab for the Treatment of Metastatic Colon Cancer: Incidence, Etiology, and Management
Introduction
Avastin (Bevacizumab), a monoclonal antibody targeting the vascular endothelial growth factor (VEGF) receptor, was recently approved by the Federal Drug Administration for use in metastatic colon cancer. This drug targets tumor angiogenesis, an important process in tumor growth and development. In a phase III trial of patients with metastatic colon cancer, Avastin in combination with the standard chemotherapy consisting of irinotecan (CPT-11), 5-fluorouracil (5-FU), and leucovorin (IFL) showed a 30% significant increase in overall survival compared with IFL alone (20.3 months vs 15.6 months, p ≤ 0.001) and progression-free survival by 71% (from 6.2 to 10.6 months, p ≤ 0.001).1 Other studies showed similar results with Avastin in combination with fluorouracil and leucovorin or fluorouracil alone.2 Since the release of these studies, Avastin has become a widely used intervention in patients with metastatic colon cancer.
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.3 As VEGF is selectively present in the neovasculature of the growing tumor,4 the systemic side effects of targeting this receptor are minimized. In the initial trials of Avastin in combination with IFL, the side effects most commonly noted, over first-line therapy alone, were hypertension, proteinuria, and diarrhea. Less common serious complications such as bleeding, thromboembolic events, and bowel perforation occurred with a frequency of less than 2%.2 Bowel perforation occurred in 1.5% of patients in the phase III trial5 and in 1.6% of patients in subsequent surveillance trials, including 1367 patients receiving Avastin in combination with first-line chemotherapy.6 Thromboembolic events are also significantly higher in patients treated with Avastin versus chemotherapy alone (3.8% vs 1.7%).7
Bowel perforation in patients undergoing treatment with Avastin remains a rare but serious complication of this chemotherapeutic agent. Immediate recognition followed by surgical intervention is the best form of management for this unusual complication. In this report, the etiology, clinical presentation, risk factors, and management of bowel perforation after administration of bevacizumab for the treatment of metastatic colon cancer are investigated.
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Case report
A 55-year-old Caucasian man with stage IIA moderately differentiated rectal adenocarcinoma presented to the Dallas Veterans Affairs Medical Center (DVAMC) with acute abdominal pain. He had initially presented to the DVAMC in August 2003 with a lower gastrointestinal bleed and a mass on digital rectal examination. Biopsies showed rectal adenocarcinoma. He underwent neoadjuvant chemoradiation with 2 cycles of 5-FU and leucovorin and 5040 cGy to the region of the tumor followed 6 weeks later by
Discussion
Avastin trials in combination with various first-line chemotherapy drugs showed bowel perforation in 1.5% to 1.6% of patients.8, 9 The location of these perforations in phase III trial patients included gastric, small bowel, and large bowel, with the most common being large bowel, as in the current case.10 A proposed common predisposing factor in the 6 patients presenting with gastrointestinal perforation during the phase III trial was intra-abdominal inflammation caused by peptic ulcer
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