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Plasma cytokeratin‐18 concentrations as noninvasive biomarker of early gastrointestinal toxicosis in dogs receiving toceranib

Kovac, Rachel L., Ballash, Gregory, Fenger, Joelle, London, Cheryl, Warry, Emma
Journal of veterinary internal medicine 2018 v.32 no.6 pp. 2061-2068
biomarkers, cohort studies, dogs, gastrointestinal system, mast cells, phosphates, poisoning, vascular endothelial growth factors, veterinary medicine
BACKGROUND: No biomarkers for the early detection of gastrointestinal (GI) toxicosis secondary to antineoplastic treatment are recognized in veterinary medicine. Toceranib causes GI toxicosis in dogs. HYPOTHESIS/OBJECTIVE: To assess if changes in plasma cytokeratin 18 (CK18) concentration, measured in dogs being treated with toceranib phosphate, can predict the onset of GI toxicosis. We hypothesize that an increase in CK18 concentrations will be detected before the development of GI toxicosis in dogs treated with toceranib phosphate. ANIMALS: Twenty healthy client‐owned dogs and 25 client‐owned dogs with surgically excised mast cell tumor (MCT). METHODS: Prospective cohort study. Dogs were treated with toceranib (2.75 mg/kg PO q48h). Plasma was collected weekly for 4 weeks. Plasma CK18 concentration was measured on days 0, 7, 14, 21, and 28. vascular endothelial growth factor was measured on days 0 and 28. RESULTS: Mean plasma CK18 concentration on day 0 in dogs with MCT was not significantly different than healthy controls (313.5 ± 592.8 pg/mL, 119.7 ± 76.9 pg/mL, mean ± SD P = 0.27). Mean plasma CK18 concentration decreased by 98.69 pg/mL from day 0 to day 28 (P < 0.001). Plasma CK18 concentration was not a significant predictor of the development of signs of GI toxicosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma CK18 concentration was not a clinically useful biomarker for the early detection of GI toxicosis secondary to toceranib administration in dogs with MCTs.