Effect of Sunitinib on Functional Reproductive Outcome in a Rabbit Model

Capsule:
This study evaluated the effect of short-term postoperative sunitinib administration on reproductive function after surgical uterine abrasion in a rabbit model, and found that it ameliorated adhesion-induced reproductive aberrations.

Authors:
Erica M. Fallon, M.D., Deepika Nehra, M.D., Hau D. Le, M.D., Arthur P. Nedder, D.V.M., Lankai Guo, M.S., Paul D. Mitchell, M.S., Bo R. Rueda, Ph.D., Mark Puder, M.D., Ph.D.

Volume 98, Issue 2 , Pages 496-502, August 2012

Abstract:

Objective:
To determine the effect of sunitinib (Sutent; SU11248; Pfizer), a US Food and Drug Administration-approved receptor tyrosine kinase inhibitor previously shown to reduce de novo pelvic adhesion formation, on reproductive function after surgical uterine abrasion in a rabbit model.

Design:
Randomized placebo-controlled study.

Setting:
Large animal facility within an academic hospital.

Animal(s):
Thirty New Zealand White adult female rabbits (2.2–3.0 kg).

Intervention(s):
Administration of 11 doses (one preoperative and 10 postoperative) of oral sunitinib (10 mg/kg/d) or placebo.

Main Outcome Measure(s):
Effect of short-term postoperative sunitinib administration on reproductive function after surgical uterine abrasion.

Result(s):
All animals were impregnated and survived until designated euthanasia. Sunitinib-treated animals had a larger average litter size (7.7 ± 1.9 vs. 5.6 ± 2.7 kits) and offspring viability (7.1 ± 2.7 vs. 3.5 ± 3.2 kits) compared with placebo-treated animals. There was no difference in gestational length or aberration in the maintainence of fertility. There were no gross abnormalities, detectable birth defects, or growth disparity in offspring from sunitinib versus placebo-treated mothers. The adhesion burden identified at euthanasia after parturition was lower in sunitinib compared with placebo-treated animals (N = 10/group).

Conclusion(s):
Sunitinib ameliorated adhesion-induced reproductive aberrations after surgical uterine abrasion and may be an efficacious strategy to reduce postoperative pelvic adhesions.

  • While Tyrosine Kinase Inhibitors (TKIs) have been used for many years for clear cell carcinoma variants of renal cell carcinoma by urologists, this is a novel and potentially very high impact study. Trials of neo-adjuvant TKI use in renal cell carcinoma patients have interestingly, failed to show significant problems with wound complications in the post-op period as many anticipated. Obviously, this is an alternate and novel use. The challenge of this work will undoubtedly be how to translate this to human studies but it has significant clinical potential.

  • jessie.dorais

    It would be very interesting to perform a similar study design in humans to assess the extent to which sunitinib may decrease adhesion related infertility and health care costs.

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