Evaluation of anastomotic strength and drug safety after short-term sunitinib administration in rabbits
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Published on: May 11, 2011
Erica M Fallon1, Deepika Nehra1, Sarah J Carlson1
1Department of Surgery and The Vascular Biology Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
Background:
Sunitinib (Sutent) is a Food and Drug Administration-approved receptor tyrosine kinase inhibitor found to reduce postoperative adhesion formation in animal models. The objective of the present study was to evaluate anastomotic healing and potential drug-related toxicities after short-term sunitinib administration in New Zealand White rabbits.
Materials And Methods:
Under an approved study protocol, 40 rabbits underwent a laparotomy followed by colonic transection and anastomosis. Animals were randomly assigned to treatment with oral sunitinib (10 mg/kg/d) or placebo, received one preoperative dose followed by 10 postoperative doses, and were divided into two groups following the procedure: group I animals were euthanized on completion of drug treatment and group II animals were euthanized 30 d after completion of treatment. Prior to study completion, animals underwent an echocardiogram and laboratory test results were obtained. At necropsy, intestinal bursting strength (in mmHg) was evaluated.
Results:
All animals survived until designated euthanasia. There was no evidence of intra-abdominal sepsis or intestinal obstruction. Sunitinib-treated animals were found to have lower intestinal anastomotic strength compared with placebo-treated animals, as measured by bursting pressure at euthanasia, and a greater percentage of bursting at the anastomosis. On echocardiography, all ejection and shortening fractions were within established normal reference values. There were no significant differences in liver enzymes between animals. There were no wound infections, dehiscence, or delayed wound healing in any animal.
Conclusions:
These results caution against the administration of sunitinib in cases involving intestinal anastomoses because of the elevated risk of anastomotic leak. No evidence of cardiotoxicity, hepatotoxicity, or detrimental effect on wound healing was found in any animal.
Insights
Sunitinib (Sutent) use in rabbits with intestinal anastomoses showed increased leak risk but no other toxicities. Further research is needed to assess its safety in surgical patients.
Area of Science:
- Surgical oncology
- Pharmacology
Background:
- Sunitinib (Sutent) is an FDA-approved receptor tyrosine kinase inhibitor.
- Animal models suggest sunitinib reduces postoperative adhesion formation.
Purpose of the Study:
- To evaluate anastomotic healing after short-term sunitinib administration in rabbits.
- To assess potential drug-related toxicities of sunitinib in this context.
Main Methods:
- 40 New Zealand White rabbits underwent colonic transection and anastomosis.
- Animals received oral sunitinib (10 mg/kg/d) or placebo, with dosing before and after surgery.
- Groups were euthanized immediately after treatment or 30 days post-treatment for analysis.
Main Results:
- Sunitinib-treated rabbits had lower anastomotic bursting strength and higher leak rates.
- No intra-abdominal sepsis, obstruction, wound infections, or delayed healing were observed.
- Echocardiograms and liver enzymes remained within normal limits, indicating no cardiotoxicity or hepatotoxicity.
Conclusions:
- Sunitinib administration poses an elevated risk of anastomotic leak in intestinal surgery.
- Short-term sunitinib use did not demonstrate cardiotoxicity, hepatotoxicity, or impaired wound healing in rabbits.
