Evaluation of palliative therapy, alone or in combination with toceranib phosphate, in dogs diagnosed with metastatic or recurrent beta-cell neoplasia.

Aims: To compare survival in dogs with recurrent or metastatic insulinomas that were treated with palliative therapy, alone or in combination with toceranib phosphate and to assess tolerability of the combined therapy in dogs.

Materials And Methods: Dogs diagnosed with insulinoma were retrospectively identified in the records of the Veterinary Teaching Hospital Complutense (Madrid, Spain). Diagnosis of insulinoma was based on clinical signs of hypoglycaemia, concentrations in serum of glucose <3.3 mmol/L and insulin >10 μIU/mL and presence of a pancreatic mass on diagnostic imaging. Dogs were treated surgically or medically, according to clinical stage established by imaging techniques, and monitored with blood and urine analyses monthly and abdominal ultrasonography every 3 months until death. Dogs that presented with metastatic disease at diagnosis or with recurrent hypoglycaemia after surgery were treated, according to the owner's decision, with one of two treatment protocols: palliative therapy alone (control group, n=7: diet, prednisone, famotidine or omeprazole, ±octreotide) or palliative therapy in combination with toceranib (treatment group, n=5; median dose of toceranib 2.52 mg/kg). Overall survival time (OST) and adverse events were compared between the two treatment groups.

Results: The OST was longer in the treatment group (median 399, min 125, max 476 days) compared to the control group (median 67, min 23, max 387 days; p=0.042). Dogs in the treatment group had a higher incidence of grade 1-2 gastrointestinal toxicity (diarrhoea) than dogs in the control group (p=0.010). In all cases, gastrointestinal toxicity was solved by temporarily discontinuing toceranib.

Conclusions And Clinical Relevance: The use of toceranib combined with palliative treatment in dogs with suspect metastatic or recurrent insulinomas increased survival time and was adequate tolerated.