Intravesical Instillation of Gemcitabine in Patients with SBC

Abstract

To determine, in phase I trial, the local and systemic toxicity and pharmacodynamics of intravesical Gemcitabine in patients with superficial bladder cancer. To evaluate, in phase II trial, the activity of this treatment against superficial bladder cancer, measuring the response of a marker lesion.

Patients and methods

In phase I trial, twelve patients with histologically confirmed carcinoma to the bladder wall (stage Ta-T1) resistant to previous administration of anti-cancer drugs or BCG were enrolled. They received intravesical Gemcitabine starting at 500 mg and increased in 500 mg increments to 2000 mg. Three patients were treated at each dose level. In phase II trial twenty four patients with superficial bladder cancer resistant to previous treatments were treated by endoscopic resection, but a single lesion less than 1 cm was left in site. Patients then received Gemcitabine 2000 mg weekly for six weeks. The marker lesion was re-analyzed by cistoscopy and patients were re-evaluated every month.

Results

The phase I trial showed no evidence of systemic toxicity and minimal local toxicity. Gemcitabine was undetectable in plasma and its inactive metabolite (2’,2’-Difluorodeoxiuridine) was present at a mean concentration of 1.39 (1.05) μmol/L.

In phase II trial, a complete response was obtained in 50% and a partial response in 29%. No response was seen in 5 patients (21%).

No patient showed signs of progression of the marker lesion nor the appearance of new lesions.

Conclusions

Intravesical Gemcitabine appears to be well tolerated with no systemic and minimal local toxicity, even at the highest dose (2000 mg). At this dose, it also shows a good ablative action on marker lesions.