Phase II trial of intravesical gemcitabine in bacille Calmette-Guérin-refractory transitional cell carcinoma of the bladder.

PURPOSE: The aim of this phase II study was to determine the efficacy of gemcitabine administered as an intravesical agent in patients with bacille Calmette-Guérin (BCG) -refractory transitional cell carcinoma of the bladder. PATIENTS AND METHODS: Patients with superficial bladder cancer refractory or intolerant to intravesical BCG therapy and refusing a cystectomy were considered eligible for the trial. Eligible patients received two courses of intravesical gemcitabine twice weekly at a dose of 2,000 mg/100 mL for 3 consecutive weeks, with each course separated by 1 week of rest. Patients were evaluated for response at 8 weeks, then every 3 months to 1 year. RESULTS: Thirty eligible patients were included on study. The median follow-up for all the patients was 19 months (range, 0 to 35 months). Of the 30 patients, 15 (50%; 95% CI, 32% to 68%) achieved a complete response (CR). Twelve patients had tumor recurrence with a median recurrence-free survival time of 3.6 months (95% CI, 2.9 to 11.0 months). Two patients maintained a CR at 23 and 29 months, respectively. The 1-year recurrence-free survival rate for patients with a CR was 21% (95% CI, 0% to 43%). Two patients progressed to a higher stage while receiving gemcitabine treatment. The median follow-up for patients who did not have a progression or a cystectomy was 19 months (range, 2 to 35 months). Eleven patients (37%) underwent a cystectomy subsequent to gemcitabine therapy. CONCLUSION: Gemcitabine has activity in a high-risk patient population and remains a viable option for some patients who refuse cystectomy.

Phase I trial of intravesical gemcitabine in bacillus Calmette-Guérin-refractory transitional-cell carcinoma of the bladder.

PURPOSE: The aim of this phase I study was to determine the safety and toxicity profile of gemcitabine administered as an intravesical agent in patients with transitional-cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS: Patients with superficial bladder cancer refractory to intravesical bacillus Calmette-Guérin (BCG) therapy and refusing a cystectomy were considered eligible for the trial. Gemcitabine was given in the bladder for 1 hour twice weekly in 100 mL sodium chloride for a total of six treatments. After a 1-week break, a second course of six treatments over 3 weeks was given, followed by response assessment. Four dose levels were explored: 500 mg, 1,000 mg, 1,500 mg, and 2,000 mg. RESULTS: Eighteen patients completed therapy: three at 500 mg, six at 1,000 mg, three at 1,500 mg, and six at 2,000 mg. No grade 3 or 4 toxicity was observed at 500 mg. At 1,000 mg, three patients developed hematuria and one had a skin reaction resembling grade 3 hand-foot syndrome. Three patients at 1,500 mg had no grade 3 or 4 toxicity. Of six patients at 2,000 mg, one had grade 3 thrombocytopenia and neutropenia without infection. Seven patients had a complete response (negative cytology and posttreatment biopsy), and four patients had a mixed response (negative bladder biopsy but positive cytology). CONCLUSION: Gemcitabine has substantial activity as an intravesical agent in BCG-refractory TCC and warrants further investigation. Therapy given twice weekly was associated with minimal bladder irritation and tolerable myelosuppression. The recommended phase II dose for twice-weekly therapy is 2,000 mg.