MP77-08 MITOGEL: OPTIMIZING DRUG DELIVERY TO THE UPPER URINARY TRACT—A PRECLINICAL EVALUATION

Abstract

You have accessJournal of UrologyBladder Cancer: Upper Tract Tumors II1 Apr 2014MP77-08 MITOGEL: OPTIMIZING DRUG DELIVERY TO THE UPPER URINARY TRACT—A PRECLINICAL EVALUATION Moran Meiron, Karim Chamie, Seth P. Lerner, Michal Jeshurun, Gil Hakim, Mark P. Schoenberg, Allan J. Pantuck, and Arie S. Belldegrun Moran MeironMoran Meiron More articles by this author , Karim ChamieKarim Chamie More articles by this author , Seth P. LernerSeth P. Lerner More articles by this author , Michal JeshurunMichal Jeshurun More articles by this author , Gil HakimGil Hakim More articles by this author , Mark P. SchoenbergMark P. Schoenberg More articles by this author , Allan J. PantuckAllan J. Pantuck More articles by this author , and Arie S. BelldegrunArie S. Belldegrun More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2471AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The insufficient exposure of upper tract urothelial carcinoma (UTUC) to adjuvant chemotherapy has impeded widespread adoption of conservative treatment of non-invasive disease. In this context, we have examined the safety and feasibility of a novel hydrogel polymer with reverse thermal-gelation properties (Mitogel)—liquid state at cold temperature and solid at body temperature—to facilitate delivery of high doses of mitomycin C (MMC) to the upper urinary tract. METHODS Using a porcine model, we instilled hydrogel polymer with MMC (Mitogel) in seven pigs. Hydrogel containing MMC (20 mg per kidney) was instilled using a 6-French open-ended catheter in a retrograde fashion. We quantified dwell time using iodinated contrast; intracavitary renal pelvic pressure using a Millar transducer; presence of extravasation via pyelogram; ureteral obstruction with serum creatinine and quantifying urine output; and systemic absorption and toxicity of MMC by determining serum MMC and evidence of myelosuppression. All animals were euthanized and a necropsy was performed to examine for histological evidence of local traumatic or inflammatory effects. RESULTS Approximately 10–15 ml of polymer was sufficient to fill the renal pelvis and calyces. The gel was radiographically evident in the calyces for three hours and in the renal pelvis for six hours. Maximum renal pelvic pressure was initially 50 cm of water and declined to a mean of 18 cm of water within 7 minutes. There was no evidence of extravasation of contrast or ureteral obstruction. Serum creatinine, measured at baseline, 7, 24, and 72 hours were 1.50±0.32, 1.80±0.15, 1.77±0.33, and 1.67±0.14, respectively. There was evidence of urine production as early as 5 minutes, even with bilateral instillation. Maximum serum MMC level was 27 ng/ml, considerably less than the toxic threshold of 400 ng/ml. There was no evidence of acute or chronic histologic changes to the collecting system even after multiple instillations. CONCLUSIONS Administration of Mitogel, a novel hydrogel polymer containing MMC, was found to be safe and feasible in this porcine model. This mode of delivery may mitigate the challenges encountered when attempting to deliver chemotherapy to the upper urinary tract. These results support the study of Mitogel as an adjuvant therapy for the treatment of UTUC in humans. © 2014FiguresReferencesRelatedDetailsCited byLaguna M (2018) Re: Genomic Characterization of Upper Tract Urothelial CarcinomaJournal of Urology, VOL. 195, NO. 6, (1719-1719), Online publication date: 1-Jun-2016. Volume 191Issue 4SApril 2014Page: e914 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Moran Meiron More articles by this author Karim Chamie More articles by this author Seth P. Lerner More articles by this author Michal Jeshurun More articles by this author Gil Hakim More articles by this author Mark P. Schoenberg More articles by this author Allan J. Pantuck More articles by this author Arie S. Belldegrun More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...