Toceranib phosphate in the management of canine insulinoma: A retrospective multicentre study of 30 cases (2009–2019)

Abstract

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.

Insulin therapy in a dog diagnosed with a metastatic insulin‐secreting neuroendocrine tumour

“…No documented outcome or specific MST was made; however, they concluded that dogs treated with toceranib had a clinical benefit. 10 After discontinuing all medical treatments for insulinoma saw no resolution of the hyperglycaemia in this dog, insulin therapy was cautiously commenced. This decision was also based on clinical concerns for the development of diabetic ketoacidosis with consistent clinical signs of DM (PUPD, weight loss, glucosuria, bilateral cataract formation), with a documented persistent hyperglycaemia (22.2 mmol/L) and ketosis (6.0 mmol/L).…”

“…Sheppard-Olivares and colleagues retrospectively reviewed 30 animals with an insulinoma treated with toceranib. 10 Nine cases that did not undergo surgical intervention received toceranib with or without concurrent prednisolone. No documented outcome or specific MST was made; however, they concluded that dogs treated with toceranib had a clinical benefit.…”

“…The most commonly prescribed medications for chronic hyperinsulinaemia management include glucocorticoids, non-diuretic benzothiadiazines (diazoxide) and tyrosine kinase inhibitors (TKIs) (toceranib phosphate). 3,[8][9][10] Octreotide and streptozocin are less commonly used medical treatments due to lack of clinical benefit, high cost and streptozotocin's reported toxicity. [11][12][13] Multiple veterinary and human databases were searched using the terms insulinoma, canine insulinoma, metastatic insulinoma, diabetes mellitus, medication-induced diabetes and medically managed insulinomas.…”

Current Trends in Diagnosis, Treatment and Prognosis of Canine Insulinoma

“…Finally, most recently, a case report and two small retrospective case series described the use of tyrosine kinase inhibitor toceranib phosphate for canine insulinomas [ 49 , 50 , 51 ]. Although some dogs in these studies were reported to have long-term glycaemic control following toceranib phosphate therapy, it is currently unclear whether this effect could be attributed to toceranib phosphate.…”

Serum insulin concentration in dogs with insulinoma as a clinical marker for presence of metastasis at the time of diagnosis

“…This treatment includes attempts to decrease insulin secretion (e.g., diazoxide, octreotide), to increase insulin resistance and promote gluconeogenesis (e.g., glucocorticoids) or cytotoxic treatment (e.g., streptozocin, tyrosine kinase inhibitors). 1,4,8,[16][17][18][19][20] Detection of metastases at the time of diagnosis is fundamental to select the most appropriate treatment approach. Their presence may influence cost of treatment, treatment success rate, and prognosis.…”