WITHDRAWN: Management of canine insulinomas with toceranib phosphate: 30 cases (2009-2019)

Abstract

BACKGROUNDInsulinomas are the most common tumour of the endocrine pancreas in dogs. These are malignant tumours with a high metastatic rate and limited efficacious chemotherapeutic options available. Recent literature supports the use of the multi-receptor tyrosine kinase inhibitor sunitinib malate for treatment of metastatic insulinoma in people. Toceranib phosphate is a veterinary targeted therapy that may provide benefit in treatment of canine insulinomas. The primary objectives of this retrospective study were to describe the control of clinical signs, response to toceranib in the case of measurable disease, and outcomes of toceranib therapy for canine insulinoma. A secondary objective was to describe the adverse effects of toceranib in dogs with insulinoma.RESULTSA medical record search identified 30 dogs diagnosed with insulinoma and treated with toceranib at five university hospitals and eight veterinary specialty referral hospitals. A majority (66.7%) of dogs with measurable disease experienced either complete response (CR), partial response (PR), or stable disease (SD) for a minimum of 10 weeks with toceranib therapy. The overall median progression free interval (PFI) was 561 days (95% confidence interval: [246, 727 days]). The overall medial survival time (OST) was 656 days [310, 1045 days]. Larger dogs were at increased risk for disease progression (P = 0.0310) and death (P = 0.0064), with every 1 kg increase in body weight resulting in hazard ratios (HRs) of 1.045 [1.003, 1.084] and 1.05 [1.012, 1.090], respectively. In addition, time to disease progression was associated with use of therapies prior to toceranib (P = 0.0050) and type of veterinary practice (P = 0.0025). The most common adverse events with toceranib therapy were grade 1 or 2 gastrointestinal toxicities.CONCLUSIONSClinical benefit was reported in the majority of dogs diagnosed with insulinoma treated with toceranib, but randomized, prospective studies are needed to assess and quantify the effect of this therapy. The most commonly observed adverse events (AEs) were grade 1 or 2 gastrointestinal AEs.