Systemic Absorption and Pharmacokinetics of Single-dose Intravesical Gemcitabine After Transurethral Resection of the Bladder in Non-muscle-invasive Bladder Cancer

Abstract

To evaluate the systemic quantitative absorption, pharmacokinetics, and toxicities of gemcitabine administered intravesically at the recommended, high-concentration dose of 40 mg/mL, immediately after transurethral resection. For a single intravesical instillation of gemcitabine after resection, 15 consecutive patients with recurrent, low-, or intermediate-risk non-muscle-invasive bladder cancer candidates were selected. The extent of resection was defined as "small" if <or= 6 excursions of the resecting loop and "large" if > 6 excursions were needed to eliminate lesions. Eight and 7 patients, underwent a small and a large resection, respectively. Immediately after surgery 2000 mg of gemcitabine in 50 mL saline was instilled and held in the bladder for 1 hour. Pharmacokinetics of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine were determined in plasma by high-performance liquid chromatography. Local and systemic toxicity were assessed. The highest mean gemcitabine concentrations were 1.38 microg/mL in small and 2.47 microg/mL in large resections. The difference was largest at 15 minutes after instillation (1.10 vs 2.47 microg/mL, P = .001). A significant difference was found between time and type of resection for gemcitabine plasma levels (P = .02) but not for 2',2'-difluorodeoxyuridine. Toxicity never exceeded grade 2. At a mean follow-up of 2 years, 9 patients (60%) were found to be recurrence-free. The systemic absorption of a single postoperative intravesical instillation of high concentration gemcitabine is proportional to the extent of resection; peak plasma concentrations reached at 15 minutes are below the levels of intravenous administration.