Prospective Evaluation of Biweekly Streptozotocin in 19 Dogs with Insulinoma

Abstract

Administration of streptozotocin (STZ) at a 21-day interval has been described in dogs with stage II and III insulinoma. Myelosuppression was not observed, suggesting the possibility of increasing dose intensity by decreasing the interval between doses. To describe the tolerability of a biweekly STZ protocol. A secondary objective was to describe the outcome of dogs treated with this protocol. Nineteen dogs with residual local, metastatic, or recurrent insulinoma. After surgery for insulinoma, or at the time of recurrence, dogs were treated with a previously described STZ and saline diuresis protocol. Treatments were administered every 14 days. All dogs received antiemetic treatment. Adverse events (AEs) were recorded and graded. Outcome endpoints assessed were progression-free survival (PFS) and survival. None of the dogs experienced neutropenia or thrombocytopenia. Mild to moderate gastrointestinal toxicity was the most common AE. Diabetes mellitus was observed in 8 dogs and, in 6, resulted in euthanasia or death. Two dogs developed nephrotoxicity manifested as Fanconi syndrome in 1 and nephrogenic diabetes insipidus in the other. Six dogs developed increased alanine amino transferase activity. Hypoglycemia at the end of the STZ infusion, resulted in collapse in 1 dog and a generalized seizure in another. The median overall PFS and survival time were 196 and 308 days, respectively. Streptozotocin can be safely administered to dogs with insulinoma, but serious AEs are possible. Additional investigation is required to better define the role of STZ in managing dogs with insulinoma.