Which factors predict bowel complications in patients with recurrent epithelial ovarian cancer being treated with bevacizumab? D.L. Richardson, F.J. Backes, J.D. Hurt, L.G. Seamon, L.J. Copeland, J.M. Fowler, D.E. Cohn, D.M. O'Malley ⁎ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, M-210 Starling Loving Hall, 320 West 10th Avenue, Columbus, OH 43210, USA abstract article info Article history: Received 9 September 2009 Available online 10 April 2010 Keywords: Bevacizumab Bowel perforation Fistula Risk factors Epithelial ovarian cancer Background. Increased rates of bowel perforation in patients with recurrent epithelial ovarian cancer (EOC) treated with bevacizumab have been reported, but the risk factors for this association are uncertain. We sought to identify factors associated with bowel perforation and fistula formation in recurrent EOC patients treated with bevacizumab. Methods. A chart review of all patients treated with bevacizumab for recurrent EOC at a single institution was performed. Pertinent patient characteristics and treatment information were collected. Univariate logistic regression was performed to analyze multiple variables. Results. One hundred twelve patients who were treated with 160 different bevacizumab regimens were identified. The median age was 60 years (range, 29–78 years). Patients had received a median of 4 prior chemotherapy regimens (range, 1–10). The median number of cycles was 4 (range, 0.5–31). Ten patients (9%) were diagnosed with bowel perforations, and another 2 patients (1.8%) were diagnosed with fistulas. The 30-day mortality following perforation was 50%, with 30% of patients dying within 1 week. Patients with rectovaginal nodularity were more likely to develop a bowel perforation or fistula than those who did not have this finding, OR = 3.64 (95% CI = 1.1 to 12.1, p = 0.04). None of the other variables were significantly associated with bowel perforations or fistula formation. Conclusions. Rectovaginal nodularity is associated with an increased risk of bowel perforation or fistula formation for patients with recurrent EOC treated with bevacizumab. Careful consideration should be given prior to initiating bevacizumab treatment in EOC patients with rectovaginal nodularity since the mortality rate with bevacizumab associated bowel perforations is 50%. © 2010 Elsevier Inc. All rights reserved. Introduction Ovarian cancer is the leading cause of gynecologic cancer deaths in the United States [1]. While the majority of patients respond to front line chemotherapy with platinum and paclitaxel, most advanced stage patients will recur. Although there are many cytotoxic agents with activity in the recurrent setting, ultimately the disease becomes chemotherapy resistant. Therefore, drugs with novel mechanisms of action designed to target specific pathways, for example angiogenesis, are being evaluated for efficacy and safety in both the front line and recurrent setting. Bevacizumab (Genentech, San Francisco, CA, USA), a monoclonal antibody against vascular endothelial growth factor, is increasingly being utilized for the treatment of recurrent ovarian cancer. It has modest activity as a single agent, with reported response rates ranging from 10% to 21% and median progression-free survival (PFS) of 4–5 months [2-5]. Combinations of bevacizumab and other novel compounds have also been studied. A phase II trial of bevacizumab combined with erlotinib (an EGFR tyrosine kinase inhibitor) demon- strated no improvement in response rates to single agent bevacizu- mab in the first phase of accrual with a concerning rate of bowel perforation. Therefore, enrollment was halted after 13 patients were treated with this combination [6]. In contrast, response rates of 24– 78% have been reported when bevacizumab has been combined with cytotoxic chemotherapy [7-10]. The large range of response rates may be attributable to different patient populations (platinum sensitivity and number of previous regimens), different cytotoxic drugs used, and different definitions for response (measurable disease versus CA125 levels). Serious bowel complications, including bowel perforations and fistulae, have been reported more commonly in ovarian cancer patients treated with bevacizumab than in most other types of cancer patients treated with this drug. Bowel perforation and fistula have been reported to occur in 0–11% of patients treated with single agent bevacizumab for recurrent ovarian cancer and in 0–9% of patients treated with bevacizumab in combination with cytotoxic Gynecologic Oncology 118 (2010) 47–51 ⁎ Corresponding author. Fax: +1 614 366 7942. E-mail address: David.O'Malley@osumc.edu (D.M. O'Malley). 0090-8258/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2010.01.011 Contents lists available at ScienceDirect Gynecologic Oncology journal homepage: www.elsevier.com/locate/ygyno