Effect of sunitinib on functional reproductive outcome in a rabbit model.
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.


METHODS
Randomized placebo-controlled study.


METHODS
Large animal facility within an academic hospital.


METHODS
Thirty New Zealand White adult female rabbits (2.2-3.0 kg).


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


METHODS
Effect of short-term postoperative sunitinib administration on reproductive function after surgical uterine abrasion.


RESULTS
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 maintenance 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).


CONCLUSIONS
Sunitinib ameliorated adhesion-induced reproductive aberrations after surgical uterine abrasion and may be an efficacious strategy to reduce postoperative pelvic adhesions.
Department of Surgery and Vascular Biology Program, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, USA.
Erica M
EM
Fallon
Deepika
D
Nehra
Hau D
HD
Le
Arthur P
AP
Nedder
Lankai
L
Guo
Paul D
PD
Mitchell
Bo R
BR
Rueda
Mark
M
Puder
D000818:Animals; D005260:Female; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D023421:Models, Animal; D011247:Pregnancy; D011256:Pregnancy Outcome; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D011817:Rabbits; D011897:Random Allocation; D012098:Reproduction / Q000187:drug effects* / Q000502:physiology; D000077210:Sunitinib; D000267:Tissue Adhesions / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D014599:Uterus / Q000187:drug effects / Q000473:pathology / Q000601:surgery
D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib