Pharmacokinetics and toxicity of an early single intravesical instillation of gemcitabine after endoscopic resection of superficial bladder cancer

Background: The tolerability and plasma absorption of gemcitabine administered at 40 mg/ml after small and extensive endoscopic transurethral resection of bladder tumors (TURB) were evaluated. Patients and Methods: Nine patients with a history of recurrent superficial bladder cancer were eligible for a single immediate, post TURB, intravesical instillation of gemcitabine. The endoscopic resection was small in 5 patients and extensive in 4. The drug was administered at 40 mg/ml concentration (2000 mg in 50 ml saline) and held in the bladder for I hour. Plasma concentrations of gemcitabine and its metabolite (2',2'-difluorodeoxyuridine) were determined with a validated HPLC assay. The blood count and chemistry were performed one day and one week postoperatively. Results: Toxicity was comparable for patients who underwent small or large TURB. The most significant side-effects were grade 2 vomiting and a transient grade 2 leukopenia after small and large TURB respectively. Mean maximum gemcitabine concentrations were 1.47 mu g/ml in small TURB and 2.8 mu g/ml in large TURB. The highest peak concentration of 4.26 mu g/ml was found after extended bladder resection. Conclusion: A single, immediate postoperative, intravesical instillation of gemcitabine at high concentration is feasible with acceptable toxicity, and it may be considered as an option taking into account patient performance status, tumor characteristics and TURB extension.