A phase I-II study on intravesical Gemcitabine in superficial bladder papillary tumors

INTRODUCTION AND OBJECTIVE: The possible role of gemcitabine inintravesical therapy of superficial transitional cell carcinoma of the bladder (TCCB) has been suggested. The European Organization for Research and Treatment of Cancer Urological Group validated the use of papillary marker lesion left in the bladder after TUR as the best tool to measure the efficacy of a drug by intravesical route against TCCB. The rsults on 27 patients are herein presented. METHODS: Twenty-seven patients, with recurrent superficial TCCB (Ta-T1, G1-G2), were treated with intravesical gemcitabine for 1 to 3 papillary marker lesions (5-15 mm) left unreseacted after TUR. Twenty-one patients (78%) had recurrent tumors after adjuvant intravesical chemotherapy (BCG in 2 cases). Multiple marker lesions, less than 10 mm, were left in 17 patients. Starting 14 days after TUR, 6 instillations of gemcitabile were given at weekly intervals. Gemcitabine, diluted in 50cc of saline solution and maintained in the bladder for two hours, was given at the dose of 500 mg, 1000 mg and 2000 mg in groups of 9 patients each. The patients, 21 days after the last instillation, were submitted to cytology, cystoscopy and TUR or cold cup biopsy of every suspicious lesion and at the sites of the marker lesions. Local and systemic toxicity was investigated at weekly intervals. Patients achieving a complete response (negative cytology, cystocopy and biopsy) received monthly maintenance up to one year. RESULTS: One patient treated at the dose of 500mg is not evaluable for response since he was lost at follow-up after the 6° instillation. Out of the remaining 26 patients, 6 (23%) achieved a complete response. Particularly, 1 (12,5%), 2 (22,2%) and 3 (33,3%) Crs were obtained at the dose of 500, 1000 and 2000 mg, respectively. A PR was obtained in 2 (22%) more patients (500 and 1000 mg). No progression in either G or T-category was detected. Bladder Tis was diagnosed in 2 complete responders at 8 and 3 months respectively. The remaining 4 patients are disease free up to 17 months. Local tolerability was excellent and never required treatment interruption. No systemic side effects were detected. CONCLUSIONS: Our experience, although preliminary, shows the excellent tolerability and the potential efficacy of gemcitabine when administered intravesically for therapy of superficial TCCB. The overall CR rate is 23% although showing a dose-related increase up to 33%. PR even if taken into account, is of uncertain prognostic significance.