Systemic absorption and pharmacokinetics of single-dose intravesical gemcitabine after transurethral resection of the bladder in non-muscle-invasive bladder cancer

Urology. 2009 Nov;74(5):1078-83. doi: 10.1016/j.urology.2009.05.094. Epub 2009 Sep 20.

Abstract

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

MeSH terms

  • Absorption
  • Administration, Intravesical
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antimetabolites, Antineoplastic / pharmacokinetics*
  • Combined Modality Therapy
  • Cystectomy / methods*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacokinetics
  • Female
  • Gemcitabine
  • Humans
  • Male
  • Middle Aged
  • Urethra
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / surgery*

Substances

  • Antimetabolites, Antineoplastic
  • Deoxycytidine
  • Gemcitabine