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

• Published in: Journal of veterinary internal medicine 2018-11, Vol.32 (6), p.2061-2068
• Main Authors: Kovac, Rachel L., Ballash, Gregory, Fenger, Joelle, London, Cheryl, Warry, Emma
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - adverse effects; biomarkers; Biomarkers - blood; cancer; canine; Case-Control Studies; chemotherapy; cohort studies; Dog Diseases - blood; Dog Diseases - chemically induced; Dog Diseases - diagnosis; Dog Diseases - drug therapy; Dogs; Female; Gastrointestinal Diseases - blood; Gastrointestinal Diseases - chemically induced; Gastrointestinal Diseases - diagnosis; Gastrointestinal Diseases - veterinary; gastrointestinal system; Indoles - adverse effects; Keratin-18 - blood; Male; mast cell tumor; mast cells; Mastocytosis - drug therapy; Mastocytosis - veterinary; phosphates; poisoning; Prospective Studies; Pyrroles - adverse effects; SMALL ANIMAL; tyrosine kinase inhibitor; Vascular Endothelial Growth Factor A - blood; vascular endothelial growth factors; veterinary medicine
• ISSN: 0891-6640; 1939-1676
• DOI: 10.1111/jvim.15326

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