UGN-101 (mitomycin gel): a novel treatment for low-grade upper tract urothelial carcinoma

Abstract

<jats:p> Upper tract urothelial carcinoma (UTUC) is a rare malignancy. The standard treatment for localized high-risk disease is radical nephroureterectomy, which confers significant morbidity and is not appropriate for all patients. Patients harboring low-risk, non-invasive disease may be candidates for organ-sparing treatment, which includes endoscopic resection with or without intracavitary drug therapy. Successful administration of intracavitary chemotherapy to the upper tracts is impeded by rapid washout of the agent and short dwell times. This has limited the clinical utility of mitomycin C for treatment of upper tract tumors, despite the successful outcomes observed in low-grade urothelial carcinoma of the bladder. Currently, there is an unmet need for development of a technically feasible and oncologically sound intracavitary therapy for management of low-grade UTUC. UGN-101 (Jelmyto™) is a novel formulation of mitomycin C that uses a unique hydrogel designed to increase urinary dwell time, and thereby efficacy of treatment. Preclinical data demonstrated promising results regarding the safety and feasibility of this agent. Preliminary results of a phase III trial (OLYMPUS study) [ClinicalTrials.gov identifier: NCT02793128] demonstrated the efficacy of UGN-101 as a successful chemo-ablative agent for low-grade upper tract tumors. UGN-101 may represent a pivotal paradigm shift in the treatment of low-grade UTUC. Indeed, the drug has recently been granted approval by the US Food and Drug Administration as the first treatment for low-grade UTUC, which may lead to significant improvements in patient care and a long-awaited decrease in the burden of disease. </jats:p>

Development of gelatin methacrylate (GelMa) hydrogels for versatile intracavitary applications

“…25 One such clinical exploration (phase-III) for intracavitary application of hydrogels was performed by Kokorovic and Matin in 2020 where they tested the applicability of mitomycin gel for the treatment of low-grade upper tract urothelial carcinoma (ClinicalTrials.gov identifier: NCT02793128). 26 The intention of formulating a hydrogel-based formulation of mitomycin was to increase the urinary dwell time of mitomycin. The group achieved promising results to treat lower-grade upper tract urothelial carcinoma indicating the potential of hydrogel systems to be beneficial, especially as a local intracavitary therapy.…”

Antegrade Instillation of UGN-101 (Mitomycin for Pyelocalyceal Solution) for Low-Grade Upper Tract Urothelial Carcinoma: Initial Clinical Experience

“…Retrograde administration can be uncomfortable and mandates administration by a physician via a cystoscope and 5Fr or 7Fr diameter ureteral catheter, typically requiring fluoroscopic guidance. 16 Antegrade administration, on the other hand, may be performed by trained nursing professionals under clean rather than sterile conditions and does not require fluoroscopy after a nephrostogram confirms placement on the day of the first instillation. The nephrostomy tube in our antegrade regimen is in place for 8 weeks total.…”

A new catheter-integrated drug-delivery system for controlled intravesical mitomycin C release

“…Indeed, limited duration of drug-exposure is a general challenge with previous IDD systems, including microparticle and nanoparticle-based applications, that eventually lose their therapeutic effect [6,[15][16][17][18][19]. In comparison, the UGN-101 (mitomycin gel), which is FDA approved and currently within phase 3 clinical trials for treatment of upper tract urothelial carcinoma, is absorbed within 4 to 6 hours after administration [20]. A prominent strength of the IPN-catheter is that the drug-reservoir can be reloaded through the balloon port to restore the optimal drug-delivery rate without the need to remove the catheter thus potentially enabling continuous treatment beyond 12 days.…”