Safety and Feasibility of Intra-Arterial Treatment of Pancreatic Cancer Using an Emulsion of Ethiodized Oil plus Bumetanide in an Oncopig Model.

PURPOSE: To evaluate the safety and feasibility of treating pancreatic tumors in an Oncopig tumor model, using bumetanide (BU)/ethiodized oil emulsion.

MATERIALS AND

METHODS

Pancreatic tumors were induced in 18 transgenic Oncopigs with inducible p53 and Kras mutations. Sixteen pigs developed tumor and were treated with intra-arterial (IA) injection of BU/ethiodized oil emulsion (n = 6) (mean injected volume, 1.8 mL of 2.9 mL of ethiodized oil + 2.10 mL [0.44 mg, 0.02 mg/kg] of BU), IA injection of ethiodized oil (n = 3), and systemic intravenous gemcitabine (n = 2). Five pigs did not receive any treatment (control). Laboratory evaluation and contrast-enhanced computed tomography (CT) scan was obtained on Days 0, 7, and 14. Necropsy was performed on Day 14. Treatment was evaluated by tumor size change, radiographic response per Response Evaluation Criteria in Solid Tumors 1.1 at Day 14, and degree of tumor necrosis on histopathological examination. One-way analysis of variance and the Tukey-Kramer post hoc test were used.

RESULTS

Median tumor diameter before treatment was 1.5 cm (interquartile range [IQR], 1.1-3.1 cm). No significant increase in the posttreatment serum lipase levels was detected in the BU/ethiodized oil group (P > .05). No clinical, radiographic, or histopathological evidence of pancreatitis was detected. Tumor size in the BU/ethiodized oil group decreased by a median of 10.3% (6.7%-13.6%, P < .05). The control group had an increase in median (IQR) tumor size by 45% (32.8%-61.4%, P < .05). The median tumor size change was significantly different between the BU/ethiodized oil and control groups (P = .01). Mean degree of necrosis was less than 10% in the treated groups (P > .05).

CONCLUSIONS

IA injection of BU/ethiodized oil emulsion is safe and feasible in treating pancreatic tumor in a transgenic porcine model.