Preclinical trial of serial MitoGel® instillations into the pelvicalyceal system of the Yorkshire swine

AUA poster presentation, Saturday, May 7, 2016 8:00 AM-10:00 AM

Preclinical trial of serial MitoGel® instillations into the pelvicalyceal system of the Yorkshire swine
Nicholas Donin*, Sandra Duarte, Los Angeles, CA, Dalit Strauss-Ayali, Yael Agmon-Gerstein, Nadav Malchi, Ra’anana, Israel, Allan Pantuck, Arie Belldegrun, Karim Chamie, Los Angeles, CA

Abstract: PD13-10
Introduction and Objectives
MitoGel® is a novel drug consisting of TC-3 – a novel hydrogel polymer that is liquid at cold temperatures, but solidifies to a gel state at body temperature – and can be combined with varying doses of mitomycin C (MMC). MitoGel® has generated interest as a treatment for upper tract urothelial cancer given its ability to provide sustained contact between MMC and the urothelium of the pelvicalyceal system. The safety of repeated instillations of MitoGel® is not fully established. Herein we present preliminary results of serial instillations of MitoGel® into the kidneys of Yorkshire swine.

Methods
MitoGel® at concentrations of 2, 4, and 8 mg/mL MMC (total dose of 14-80mg) was instilled into the pelvicalyceal systems of a total of 35 Yorkshire swine in a retrograde manner via ureteral catheter, or in the antegrade approach via nephrostomy tube; 8 animals underwent instillation of MMC in water to serve as an active comparator group; 13 animals with TC-3 without MMC to serve as a vehicle control; and 6 with water only to serve as procedure control. Overall, 10 animals received a single instillation, while the remaining 52 underwent six-serial instillations. Animals were clinically monitored for adverse events, and laboratory testing for hematologic and serum chemistry abnormalities was performed at least weekly. Necropsies were performed either the day following instillation, or 1 month later in animals receiving serial instillations. Tissues were pathologically examined.

Results
No morbidities or mortalities, or adverse clinical events were associated with the agent. There were no meaningful changes in blood counts, serum chemistries, or renal function. In the animals sacrificed the day following the final instillation, a dose related association between MitoGel® and mild-moderate macroscopic thickening and epithelial irregularities was noted. These findings were confirmed on the microscopic level, and were primarily noted in the renal pelvis and proximal ureter. In the animals sacrificed 4 weeks post-treatment, these findings were present but diminished.

Conclusions
Single and serial instillations of MitoGel® via retrograde and antegrade approaches into the pelvicalyceal system of Yorkshire swine was found to be safe as it produced no observable adverse clinical, laboratory, or histological effects.

Date & Time: May 7, 2016 8:00 AM-10:00 AM
Session Title: Bladder Cancer: Upper Tract Transitional Cell Carcinoma I
Sources of Funding: Theracoat, Ltd.

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