February 22, 2017
Colorectal stents used with Avastin (bevacizumab)
Increased risk of bowel rupture when colorectal stents and bevacizumab are used together to treat colon cancer patients
Health Canada carried out this safety review because of published studies Footnote1 that reported a potential increased risk of bowel rupture in patients that received a colorectal stent and bevacizumab treatment at the same time. Bowel rupture is when a break or hole is formed in the wall of the intestine. It is a serious medical event which may be fatal if not found and treated in time. In most cases a patient has to undergo surgery or an invasive procedure to repair the rupture. Bowel rupture is a known risk associated with the use of either colorectal stents or bevacizumab individually, and is also mentioned in the safety information for these products.
At the time of the review, Health Canada received 6 unique Canadian reportsFootnotea of bowel rupture related to the use of colorectal stents and 83 unique Canadian reportsFootnoteb of bowel rupture related to the use of bevacizumab. Only three of these reports mentioned that the two products were used together.
A number of published studies Footnote1,Footnote2,Footnote3 including a recent Canadian studyFootnote4 reported an increased risk of bowel rupture in patients treated with colorectal stents and bevacizumab-based chemotherapy, as compared to patients receiving colorectal stents and chemotherapy without bevacizumab for the treatment of bowel cancer. It was difficult to make conclusions about the extent of the increased risk because of other factors that could also have played a role in the bowel rupture, including the type of cancer itself and how much the cancer had grown or developed.
Bowel rupture can happen when colorectal stents and bevacizumab-based treatments are used together because the wall of the bowel can become weak from the treatment killing the cancer cells (tumors) that are growing in the bowel wall. Very small ruptures can form in a blocked or narrowed bowel. Bevacizumab works to slow down the growth of new blood vessels. This action may weaken the bowel wall and it could rupture from the expanded colorectal stent. Given this increased risk, some publications for healthcare professionalsFootnote 5 have indicated that treatment using colorectal stents along with bevacizumab should be carefully considered, and avoided if possible.
The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
van Halsema EE, van Hooft JE, Small AJ, et al. Perforation in colorectal stenting: a meta-analysis and a search for risk factors. Gastrointest Endosc. 2014; 79:970-982 e7.
Manes G, de Bellis M, Fuccio L, et al. Endoscopic palliation in patients with incurable malignant colorectal obstruction by means of self-expanding metal stent: analysis of results and predictors of outcomes in a large multicenter series. Arch Surg. 2011; 146:1157-1162. <https://www.ncbi.nlm.nih.gov/pubmed/22006874>
Small AJ, Coelho-Prabhu N and Baron TH. Endoscopic placement of self-expandable metal stents for malignant colorectal obstruction: long-term outcomes and complication factors. Gastrointest Endosc. 2010; 71:560-572.
Imbulgoda A, MacLean A, Heine J, et al. Colorectal perforation with intraluminal stents and bevacizumab in advanced colorectal cancer: retrospective case series and literature review. Can J Surg. 2015; 58:167-171. <http://www.ncbi.nlm.nih.gov/pubmed/25799132>
van Hooft JE, van Halsema EE, Vanbiervliet G, et al. Self-expandable metal stents for obstructing colorectal and extracolorectal cancer: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline, Endoscopy 2014; 46(11): 990-1002.