In:
Cancer Chemotherapy and Pharmacology, Springer Science and Business Media LLC, Vol. 87, No. 6 ( 2021-06), p. 799-805
Abstract:
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. Methods Pharmacokinetic parameters ( C max , T max , AUC (0–6) , λz , t ½ , and AUC inf ) 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. Results The mean age of the six participants was 69 years; most were male (5/6) and Caucasian (5/6). Mean (SD) C max was 6.24 (4.11) ng/mL and mean T max was 1.79 (1.89) hours after instillation. Mean apparent t ½ 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. Conclusion 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. Registration NCT02793128; registered June 8, 2016.
Type of Medium:
Online Resource
ISSN:
0344-5704
,
1432-0843
DOI:
10.1007/s00280-021-04246-w
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2021
detail.hit.zdb_id:
1458488-8
SSG:
15,3
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