Summary Safety Review - Colorectal Stents Used with AVASTIN (bevacizumab) - Assessing the potential increased risk of bowel rupture (intestinal perforation)

Review decision

A Summary Safety Review complements other safety related information to help Canadians make informed decisions about their use of health products. Each summary outlines what was assessed in Health Canada’s review, what was found and what action was taken by Health Canada, if any.


Issued: 2017-02-22

Product

Colorectal stents used with Avastin (bevacizumab)

Potential safety issue

Increased risk of bowel rupture when colorectal stents and bevacizumab are used together to treat colon cancer patients

Key Messages

  • Colorectal stents are medical devices licensed for sale in Canada to treat parts of the bowel that may become unusually narrowed (intestinal strictures). Avastin (bevacizumab) is a prescription health product authorized for sale in Canada as part of the treatment of certain cancers including those in the bowel.
  • Health Canada reviewed the risk of bowel rupture from colorectal stents used with bevacizumab because of published studies that reported an increased risk of bowel rupture in patients that received both treatments at the same time.
  • Health Canada's review concluded that there is limited evidence suggesting an increased risk of bowel rupture when colorectal stents and bevacizumab are used together to treat colon cancer patients.
  • Health Canada will issue a Health Product InfoWatch article to raise awareness of this potential safety issue and will continue to monitor the safety of both colorectal stents and bevacizumab.

Overview

Health Canada carried out this safety review because of published studies1 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.

Use in Canada

  • Colorectal stents are part of a group of devices known as self-expandable metallic stents and are licensed for sale in Canada to treat intestinal strictures. A stent is put into the unusually narrow part of the bowel (the intestinal stricture) and it expands as a tube-shaped frame to keep the bowel passage opened.
  • Bevacizumab (marketed under the brand name Avastin) is a health product authorized for sale in Canada as part of the treatment, along with a specific type of chemotherapy, for certain cancers including those in the bowel. It is available as a solution for injection

Safety Review Findings

  • At the time of the review, Health Canada received 6 unique Canadian reportsa of bowel rupture related to the use of colorectal stents and 83 unique Canadian reportsb 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 studies1,2,3 including a recent Canadian study4 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 professionals5 have indicated that treatment using colorectal stents along with bevacizumab should be carefully considered, and avoided if possible.

Conclusions and actions

  • Health Canada's review concluded that there is limited evidence at this time suggesting an increased risk of bowel rupture when colorectal stents and bevacizumab are used together to treat colon cancer patients.
  • Health Canada will issue a Health Product InfoWatch article to raise awareness of this potential safety issue. Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of these health products.
  • Health Canada will continue to monitor safety information involving colorectal stents and bevacizumab, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified.

Additional information

The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of these products both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

References

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.

Footnotes

  1. Incident reports as retrieved from the Health Canada Medical Device System.
  2. Canadian reports can be accessed through the Canada Vigilance Online Database.

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