Bevacizumab-Induced Nasal Septum Perforation

Abstract

A 53-year-old white male presented for evaluation and treatment after transverse colectomy for colon cancer. Postoperative computerized tomography and positron emission tomography scans confirmed synchronous liver metastases. The patient was started on 5-fluorouracil (5FU), leucovorin, and oxaliplatin (Eloxatin ® ; Sanofi-Synthelabo Inc., New York, http://www.sanofi-synthelabo.us) (mFOLFOX) in combination with bevacizumab (Avastin ® ; Genentech, Inc., South San Francisco, CA, http://www. gene.com). His concurrent medications included metoprolol (Lopressor ® ; Novartis Pharmaceuticals Corporation, East Hanover, NJ, http://www.pharma.us.novartis.com) and irbesartan (Avapro ® ; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com) for hypertension and clopidogrel (Plavix ® ; Bristol-Myers Squibb), atorvastatin (Lipitor ® ; Pfizer Pharmaceuticals, New York, http://www.pfizer. com), and aspirin for a history of single vessel coronary artery disease status post angioplasty. After three cycles of treatment with mFOLFOX/bevacizumab, the patient noted scabbing and irritation in the inferior part of the nasal septum associated with occasional bleeding. Physical examination revealed a small mucosal break. He denied any nasal instrumentation or manipulation, any history of cocaine abuse, or use of intranasal medications. After six cycles of chemotherapy, he complained of a “hole in the nose” in association with scant bloody discharge. Physical examination revealed a nasal septum perforation without any masses. A consultation with a head and neck specialist confirmed these findings on rhinoscopy. The mucosa was noted to be dry and scaly and slightly erythematous around the edges of the perforation. There were no visible masses or other abnormalities noted in the nasal vestibules. Figure 1 shows the nasal septal defect. Bevacizumab is a recombinant monoclonal immunoglobulin G1 antibody that selectively binds to vascular endothelial growth factor (VEGF), thus preventing its binding to the VEGF receptors VEGFR-1 and VEGFR-2 and inhibiting angiogenesis [1]. The combination of bevacizumab with irinotecan (Camptosar ® ; Pfizer Pharmaceuticals), 5-FU, and leucovorin has been shown to produce a superior response rate, time to progression, and overall survival in the first-line treatment of metastatic colon cancer [2]. Similarly, the combination of bevacizumab with FOLFOX has resulted in superior response rates, time to progression, and overall survival in the second-line treatment of metastatic colorectal cancer [3]. Bevacizumab has been associated with a 1% risk for bowel perforation when given as a single agent or in combination with FOLFOX [3]. Furthermore, a higher risk for wound healing complications and bleeding has been documented in patients who started treatment within 60 days from surgery [4]. Nasal