Safety evaluation of targeted osmotic lysis therapy in Beagles

The objective of this study was to satisfy the US FDA's Center for Devices and Radiological Health regarding the safety of targeted osmotic lysis (TOL), a novel treatment for advanced carcinomas, in Beagle dogs.

12 intact Beagle dogs, 6 males and 6 females, were divided into 2 treatment groups of 6, each receiving 3 TOL cycles. For each 6-day cycle, digoxin was administered orally at 0.007 mg/kg q 12 h X 6 days to achieve steady-state plasma concentrations. On days 5 and 6 of each cycle, the animals were exposed to pulsed electric field (PEF) stimulation at a field strength of either 18 or 40 V/min for 2 hours. Following the completion of cycles 1 and 2, animals were observed for 7 days. On the day following the end of cycle 3, the animals were euthanized. A complete macroscopic examination was performed, and tissues were collected for microscopic examination.

As there were no concurrent untreated control animals, only qualitative comparisons were performed to assess potential differences between group 1, which received the digoxin plus 18 V/min PEF, and group 2, which received digoxin plus 40 V/min PEF. No adverse events related to TOL exposure were observed in either group.

Neither group demonstrated gross or microscopic lesions following 3 rounds of exposure to TOL.

Due to the lack of toxicity noted in the treated animals, TOL warrants consideration as either a standalone treatment option or as an adjunct to surgery or chemotherapy for managing malignant cancer.