To evaluate the pharmacokinetic properties of UGN-101, a mitomycin-containing reverse thermal gel used as primary chemoablative treatment for low-grade upper tract urothelial carcinoma (UTUC), in a subset of patients participating in a phase 3 clinical trial.
Pharmacokinetic parameters (Cmax, Tmax, AUC(0-6), λz, t½, and AUCinf) were evaluated in six participants (male or female, ≥ 18 years) with biopsy-proven, low-grade UTUC who received the first of 6 once-weekly instillations of UGN-101 to the renal pelvis and calyces via retrograde ureteral catheter. Plasma samples were collected prior to instillation and 30 min, 1, 2, 3, 4, 5, and 6 h post-instillation. Safety was assessed by laboratory evaluations, physical exam, and adverse event monitoring.
The mean age of the six participants was 69 years; most were male (5/6) and Caucasian (5/6). Mean (SD) Cmax was 6.24 (4.11) ng/mL and mean Tmax was 1.79 (1.89) hours after instillation. Mean apparent t½ following instillation was 1.27 (0.63) hours. Mean total systemic exposure to mitomycin up to 6 h post-instillation was 20.30 (19.69) ng h/mL. At 6 h post-instillation, mitomycin plasma concentrations of 5/6 participants were < 2 ng/mL. There were no clinically important adverse events or changes in laboratory values in any participant after a single instillation of UGN-101.
The reverse thermal gel formulation of UGN-101 is associated with higher concentration and extended dwell time of mitomycin in contact with the urothelium of the upper urinary tract while limiting systemic absorption of mitomycin.
NCT02793128; registered June 8, 2016.
Cancer chemotherapy and pharmacology. 2021 Mar 07 [Epub ahead of print]
Ahmad Shabsigh, Nir Kleinmann, Angela B Smith, Douglas Scherr, Elyse Seltzer, Mark Schoenberg, Seth P Lerner
Department of Urology, The Ohio State University Comprehensive Cancer Center, 300 W 10th Ave, Columbus, OH, 43210, USA. ., Department of Urology, Sheba Medical Center, Ramat Gan, Israel., Department of Urology, University of North Carolina School of Medicine, Chapel Hill, NC, USA., Department of Urology, Weill Medical College of Cornell University, New York, NY, USA., UroGen Pharma, New York, NY, USA., Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA.