Phase I pharmacokinetic study of a single intravesical instillation of gemcitabine administered immediately after transurethral resection plus multiple random biopsies in patients with superficial bladder cancer

Juan Palou, Antonio Carcas, Jose Segarra, Blanca Duque, Jose Salvador, Ignacio Garcia-Ribas, Humberto Villavicencio

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32 Citations (Scopus)

Abstract

Purpose: In this phase I study we determined the pharmacokinetic and toxicity profiles of a single intravesical instillation of gemcitabine administered immediately after complete transurethral resection (TUR) plus multiple random biopsies. Materials and Methods: Ten patients with superficial bladder cancer clinically staged as Ta/T1 with no carcinoma in situ were included. A single dose of gemcitabine was administered intravesically immediately after TUR plus 6 random biopsies. Five patients received 1,500 mg and 5 received 2,000 mg diluted in 100 ml saline. Retention time in the bladder was 60 minutes. Concentrations of gemcitabine and dFdU (2′,2′- difluoro-2′-deoxyuridine) were determined by high pressure liquid chromatography assay. Results: Treatment was clinically well tolerated in all patients. Two patients in the 1,500 mg group had minimal hipogastric discomfort and 1 in the 2,000 mg group had grade 1 bladder spasms. There was no remarkable systemic toxicity on hematology or biochemistry at any dose level on day 12 or 30. One patient per dose level showed tumor recurrence on 3-month repeat cystourethroscopy. Mean maximum gemcitabine concentration was 1.8 μg/ml and the mean last AUC was 158 μg/ml*minute. There was large interpatient variability but no significant differences between the 2 dose levels. Conclusions: Single intravesical instillation of gemcitabine immediately after TUR and multiple random biopsies for superficial bladder cancer are a safe and well tolerated treatment. The favorable toxicity and pharmacokinetic profiles of intravesical gemcitabine support future phase II studies with this agent.
Original languageEnglish
Pages (from-to)485-488
JournalJournal of Urology
Volume172
Issue number2
DOIs
Publication statusPublished - 1 Jan 2004

Keywords

  • Administration, intravesical
  • Bladder
  • Bladder neoplasms
  • Gemcitabine

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