Systemic Absorption and Pharmacokinetics of Single-dose Early Intravesical Mitomycin C After Transurethral Resection of Non-muscle-invasive Bladder Cancer

ObjectiveTo study the systemic absorption and pharmacokinetics of a single dose of intravesical mitomycin C (MMC) given immediately after transurethral resection of bladder tumor (TURBT).MethodsFourteen patients with primary or recurrent non-muscle-invasive bladder cancer were eligible for a single early intravesical instillation of MMC (40 mg in 50 mL distilled water) administered immediately after TURBT. Blood samples were obtained at baseline and at 20, 40, 60 (time of voiding), 90, 120, and 150 minutes after instillation. Concentrations of the drug were determined by validated high-performance liquid chromatography assay. During TURBT, we counted the number of excursions of the resecting loop required to completely eradicate the tumor, including a portion of the underlying muscular wall. TURBTs were categorized as small and large, defined as requiring ≤6 or >6 full excursions of the resecting loop, respectively.ResultsMaximal MMC plasma concentrations were reached 40 minutes after instillation. At 150 minutes, only minimal drug plasma levels were detectable in 4 patients. The highest plasma peak was 49.25 ng/mL. In the first samples, at 20 minutes after instillation, the plasma concentration of MMC was significantly correlated with the extent of TURBT (P = .026). Four patients (28.6%) complained of G1 side effects, 3 after a large TURBT and 1 after a small TURBT, and 1 patient had G2 dysuria after a large TURBT.ConclusionLow peak blood levels of MMC are observed after a single-dose intravesical instillation immediately after TURBT, with low systemic and local toxicity. The early absorption rate depends on TURBT extension.