Bowel perforation and fistula formation in colorectal cancer patients treated on Eastern Cooperative Oncology Group (ECOG) studies E2200 and E3200

Abstract

3017 Background: The addition of bevacizumab (rhu-anti-VEGF) to frontline chemotherapy for advanced colorectal cancer (CRC) improves survival. Bowel perforation and fistula formation have been reported in colorectal cancer patients treated with bevacizumab. Methods: ECOG conducted two trials of bevacizumab in patients with metastatic CRC: as frontline chemotherapy with IFL (E2200) and second line therapy with 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX4) (E3200). Toxicity forms and severe adverse event reports were reviewed for bowel perforation and fistula formation. Results: In E2200, 86 patients were treated. There were 2 reports of bowel perforation and 2 reports of enterocutaneous fistulae. The bowel perforations occurred in cycles 1 and 10; both occurred at anastomotic sites. One perforation occurred 27 days after hemicolectomy. The fistulae occurred in cycles 1 and 6. In E3200, 824 patients were treated (290 chemotherapy alone, 292 chemotherapy with bevacizumab, and 242 bevacizumab alone). There were 5 bowel perforations; all occurred in patients treated with bevacizumab (<1%). There were 3 fistulae, one in each arm of the study. All but one of the bowel perforations occurred in cycle 1 of therapy; one occurred in cycle 3. Three patients with perforation had invasive procedures to the gastrointestinal tract within 3 weeks of starting bevacizumab. The fistulae were noted at cycles 2, 3, and 10. Two were enterocutaneous and one was enterovaginal. All bowel perforations presented with pain: abdominal pain in 5, hip/lower extremity pain in 2, and rectal pain in one. Overall, 2 patients with perforation died of this complication. Conclusions: Use of bevacizumab in colorectal cancer patients may be associated with an increased risk of bowel perforation and fistula formation. Although an uncommon occurrence, bowel perforation should be considered in colorectal cancer patients treated with bevacizumab who develop symptoms consistent with this diagnosis. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech; Sanofi-Synthelabo Sanofi-Synthelabo Genentech; Pfizer (Pharmacia)