Intravesical administration of gemcitabine in superficial bladder cancer: a phase I study with pharmacodynamic evaluation.

OBJECTIVE To determine, in a phase I trial, the local and systemic toxicity and pharmacodynamics of intravesical gemcitabine in patients with superficial bladder cancer. PATIENTS AND METHODS Twelve patients with histologically confirmed carcinoma localized to the bladder wall (stage T1 or Ta) resistant to previous administration of anticancer drugs and/or of bacille Calmette-Guerin were enrolled. They initially received intravesical gemcitabine starting at 500 mg and increased in 500 mg increments to 2000 mg. Three patients were treated at each dose level. RESULTS There was no evidence of systemic toxicity and local toxicity was minimal. A pharmacological evaluation showed that gemcitabine was undetectable in plasma and its inactive metabolite (2′,2′-difluorodeoxyuridine) was present at a mean (sd) concentration of 1.39 (1.05) µmol/L. Deoxycytidine kinase was present in tumour tissue samples, and its activity was 27.3 (12.6) pmol/h/mg tissue; deoxycytidine deaminase activity varied from undetectable to 616 pmol/h/mg tissue. CONCLUSION Intravesical gemcitabine appears to be well tolerated with no systemic and minimal local toxicity even at the highest dose (2000 mg). A phase II trial of intravesical gemcitabine at 2000 mg given weekly for six consecutive weeks is now in progress in patients with superficial bladder cancer.