Thermo Reversible Hydrogel Based Delivery of Mitomycin C (UGN-101) for Treatment of Upper Tract Urothelial Carcinoma (UTUC)

Abstract

Background: There is an unmet need for an effective local treatment of upper tract urothelial carcinoma (UTUC). Drug delivery to the pyelocaliceal system and pursuant efficacy of intracavitary therapy is limited by urine production that washes the drug away, shortening dwell time and direct contact with the urothelium. Successful endoscopic management is often dictated by lesion size, grade, and focality. A thermo-reversible hydrogel formulation of Mitomycin C (UGN-101, formerly MitoGel) was developed and has demonstrated the safety and feasibility of increased time of the drug in the pyelocaliceal system resulting in chemoablation of tumors. Objectives: To examine the efficacy and safety of UGN-101 used for chemoablation of UTUC. Methods: There were 22 patients approved for compassionate use treatment at 14 institutions. Six-weekly instillations of UGN-101 were administered via ureteral catheter or percutaneous nephrostomy. Ureteroscopy was performed 2-6 weeks following treatment completion for response determination. Adverse events were recorded throughout treatment. Patients were followed up according to the standard of care of each center.

Durability of Response to Primary Chemoablation of Low-Grade Upper Tract Urothelial Carcinoma Using UGN-101, a Mitomycin-Containing Reverse Thermal Gel: OLYMPUS Trial Final Report

“…4 Liquid when chilled, UGN-101 is instilled via ureteral catheter or nephrostomy tube and becomes a semisolid gel at body temperature that dissolves during urine production over 4-6 hours, resulting in increased dwell time at the tumor site. 5 We previously reported interim results from OLYMPUS, a phase 3 clinical trial that evaluated UGN-101 for treatment of low-grade UTUC. 6 The trial's primary endpoint was complete eradication of disease in the ipsilateral pyelocalyceal system (defined as negative ureteroscopic evaluation, negative cytology, and negative for-cause biopsy) 4-6 weeks following 6 weekly induction instillations of UGN-101.…”

Novel Thermo-Sensitive Hydrogel Therapy for Low-Grade Upper Tract Urothelial Carcinoma

“…The effectiveness of intravesical therapy is dependent on high drug concentration and dwell time to maximize exposure to the bladder mucosa. 2…”

Final Results of a Phase I Trial of WST-11 (TOOKAD Soluble) Vascular-targeted Photodynamic Therapy for Upper Tract Urothelial Carcinoma

“…22 With mitomycin thermal gel, which requires 6 weekly catheter-based instillations, events such as acute kidney injury (9%), myelosuppression (9%), ureteral stricture preventing further instillations (5%), and treatment discontinuation (27%) were described in the original report in which a 36% CR rate was seen. 23 In the Phase 3 trial of primary chemoablation with mitomycin thermal gel for low-grade UTUC (OLYMPUS), a 59% CR rate was seen, while 44% of patients developed ureteric stenosis. 24 Our study demonstrated similar efficacy, in both low- and high-grade tumors, with no cases of treatment-related ureteral stricture.…”