Background: Insulinomas are the most common tumour of the endocrine pancreas in dogs. These malignant tumours have a high metastatic rate and limited chemotherapeutic options. The multi‐receptor tyrosine kinase inhibitor sunitinib malate has benefit in the treatment of metastatic insulinoma in people. Toceranib phosphate, an analogous veterinary agent, may provide benefit for dogs. Methods: A retrospective study describing the extent and duration of clinical outcomes and adverse events (AEs) in dogs diagnosed with insulinoma and receiving toceranib. Results: Records for 30 dogs diagnosed with insulinoma and having received toceranib were identified from a medical record search of five university and eight referral hospitals. The median progression‐free interval and overall survival time were 561 days (95% confidence interval (CI): [246, 727 days]) and 656 days (95% CI: [310, 1045 days]), respectively. Of the dogs for which the canine Response evaluation criteria for solid tumours tool could be applied, the majority (66.7%) showed either a complete response, partial response or stable disease. Time to clinical progression was associated with prior intervention and type of veterinary practice. Larger dogs were at increased risk for disease progression and death. No novel AEs were reported. Conclusions: Most dogs diagnosed with insulinoma and receiving toceranib appeared to have a clinical benefit. Randomised, prospective studies are needed to better elucidate and objectively quantify the potential effect and survival benefit of toceranib therapy for management of insulinoma in dogs.

Background: Canine urothelial carcinoma is the most common form of canine bladder cancer. Treatment with chemotherapy has variable response rates leading to most dogs succumbing to their disease within a year. Cannabidiol is an emerging treatment within the field of oncology. In reportedin vivostudies, cannabidiol has induced apoptosis, reduced cell migration, and acted as a chemotherapy sensitizer in various human tumor types. The aim of this study was to characterize the effects of cannabidiol on canine urothelial carcinoma cell viability and apoptosis as both a single agent and in combination with chemotherapyin vitro.Results: Cannabidiol reduced cell viability and induced apoptosis in canine urothelial cells as determined by crystal violet viability assay and annexin V/propidium iodide flow cytometry. Furthermore, combinations of cannabidiol with mitoxantrone and vinblastine chemotherapy yielded significantly reduced cell viability and increased apoptosis compared to single agent treatment alone. The drug interactions were deemed synergistic based on combination index calculations. Conversely, the combination of cannabidiol and carboplatin did not result in decreased cell viability and increased apoptosis compared to single agent treatment. Combination index calculations suggested an antagonistic interaction between these drugs. Finally, the combination of the non-steroidal anti-inflammatory drug piroxicam with cannabidiol did not significantly affect cell viability, although, some cell lines demonstrated decreased cell viability when mitoxantrone was combined with piroxicam.Conclusions: Cannabidiol showed promising results as a single agent or in combination with mitoxantrone and vinblastine for treatment of canine urothelial carcinoma cells. Further studies are justified to investigate whether these results are translatablein vivo.

The endocannabinoid system is increasingly being implicated in the pathogenesis and progression of various human cancers. Specifically, increased levels of 2-arachidonoylglycerol (2-AG) and oleoythanolamide (OEA) have been demonstrated in human diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL) patients, respectively. The objectives of this paper were to compare 2-AG, OEA, N-arachidonoylethanolamine (AEA), and palmitoylethanolamide (PEA) levels between dogs with multicentric lymphoma and healthy control dogs. In addition, evaluate 2-AG, OEA, AEA, and PEA levels as biomarkers for progression free interval (PFI) and overall survival time (OST) in the dogs with lymphoma. The study consisted of 26 dogs with multicentric B cell lymphoma, 14 dogs with multicentric T cell lymphoma, and 12 healthy control dogs. Serum 2-AG, OEA, AEA, and PEA levels were measured using liquid chromatography combined with tandem mass spectrometry (LC—MS/MS) in dogs with lymphoma and in healthy dogs. OEA, AEA, and PEA levels were significantly elevated in dogs with lymphoma compared to healthy controls (p< 0.05). Total AG was significantly higher in healthy control dogs (p= 0.049). There was no significant difference between dogs with B cell and T cell lymphoma for any of the measured endocannabinoids. Elevated PEA was significantly associated with decreased PFI (p= 0.04) in dogs with lymphoma with a hazards ratio of 1.816 [95% Confidence Interval (CI): 1.020–3.232]. Overall, dogs with lymphoma have elevated levels of OEA, AEA, and PEA. PEA levels have the potential to be a prognostic biomarker.