Over the last several years, research has been directed for improving the deliverability of topical agents to the upper tracts. One of the challenges is difficulty concentrating therapeutic levels of these agents in the upper tract for more than a brief period of time secondary to ureteral peristalsis rapidly draining topic treatment from the pelvis and ureter. Specifically, mitomycin C exposure time to the urothelium is critical for efficacy. RTGel is a reverse-thermal hydrogel composed of a combination of polymers that allows it to exist as a liquid at cold temperatures, but solidifies to a gel state at body temperature. This product was developed to address the constraints of the upper urinary tract, where continuous urine production and ureteral peristalsis prevents drug retention in the upper tract. Subsequently, MitoGel (or UGN101) was developed as a novel formulation of RTGel combined with mitomycin C.
The hypothesis for MitoGel is that upon delivery to the upper urinary tract, MitoGel would gelatinize and urine would produce a slow dissolution of the gel, allowing a sustained release of mitomycin C into the upper tract allowing prolonged exposure to the urothelium. Using a preclinical swine animal model (n=23), Donin et al noted that after antegrade instillation of MitoGel, the product remained visible in the pelvicalyceal system on fluoroscopic and computed tomography imaging for 4-6 hours after instillation2. Dr. Chamie and his colleagues from UCLA subsequently confirmed these safety results in a study assessing six once-weekly unilateral retrograde instillations of Mitogel3.
The OLYMPUS trial for UGN101 (NCT02793128) is a prospective single-arm ongoing clinical trial designed to assess the efficacy, safety, and tolerability of MitoGel in patients with low grade, noninvasive upper tract urothelial cancer. Eligible patients are treated with MitoGel once weekly for a total of six times in a retrograde fashion; patients demonstrating a complete response are treated with MitoGel once monthly for a total of 11 instillations as maintenance, or until first recurrence. The primary outcomes are complete response rate defined as the percent of patients with complete response at the primary disease evaluation visit (~11 weeks), and adverse event rates (over ~2 years).
- Long-term durability of complete response (12 months)
- Complete response rates at 3, 6, and 9 months
- Partial response to treatment (~11 weeks)
- Mitomycin C level in blood plasma
Dr. Chamie then presented several cases to demonstrate utilization of UGN101, which can be performed in an office or operating room setting. The kit includes a UGN101 instillation injector, syringes and instructions for mixing the product. The cases start with cystoscopic placement of a 5 Fr open ended ureteral catheter used for obtaining a pre-treatment retrograde pyelogram and also to ensure the catheter is in the appropriate location. It is important to note that the kit also comes with a 7Fr Kumpe catheter, as the gel cannot be expelled through a 5Fr catheter secondary to the high pressure associated with gel injection. Once the 5Fr catheter is exchanged for the 7Fr catheter, it is important to aspirate all of the contrast out of the renal pelvis prior to placing the UGN101 gel. It is also important that the company specific injector is used for injecting the gel, given the viscosity of the gel at room temperature. Once the gel is instilled, Dr. Chamie notes that the catheter and injecting syringe are removed en bloc. Specifically, when the tumor is visible on retrograde pyelogram, some surgeons will inject roughly half of UGN101 directly into the tumor/affected calyx and the remainder into the renal pelvis.
Presented by: Karim Chamie, University of California-Los Angeles, Los Angeles, CA
Written By: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University - Medical College of Georgiam @zklaassen_md at American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois
- Upfill-Brown A, Lenis AT, Faiena I, et al. Treatment utilization and overall survival in patients receiving radical nephroureterectomy versus endoscopic management for upper tract urothelial carcinoma: An evaluation of updated treatment guidelines. World J Urol 2018 Sep 28 [Epub ahead of print].
- Donin NM, Duarte S, Lenis AT, Caliliw R, Torres C, Smithson A, et al. Sustained-release Formulation of Mitomycin C to the Upper Urinary Tract Using a Thermosensitive Polymer: A Preclinical Study. Urology. 2017;99:270-7.
- Donin NM, Strauss-Ayali D, Agmon-Gerstein Y, Malchi N, Lenis AT, Holden S, et al. Serial retrograde instillations of sustained release formulation of mitomycin C to the upper urinary tract of the Yorkshire swine using a thermosensitive polymer: Safety and feasibility. Urol Oncol. 2017;35:272-8.