Intravesical gemcitabine in superficial bladder tumors. Results of a phase I-II study

Abstract

the good tolerability of intravesical gemcitabine have been recently published. The evaluation of the activity on a papillary marker lesion is the best tool to measure the efficacy of a drug by intravesical route against superficial transitional cell carcinoma of the bladder (TCCB). The scientific background and the ethical acceptability of this approach have been validated by the European Organization for Research and Treatment of Cancer Urological Group. The aim of the present study was to evaluate the ablative efficacy of weekly intravesical instillations of gemcitabine against a histologically proven papillary marker lesion. MATERIAL & METHODS: Twenty-seven patients, affected by recurrent multiple superficial TCCB (Ta-Tl, Gl-G2), were treated with intravesical gemcitabine after a transurethral resection (TUR) during which 1 to 3 papillary marker lesions (5-15 mm in diameter) were left unresected. High grade (G3) hanours and Tis were excluded. Twenty-one patients (77.7%) had been treated in the past with adjuvant intravesical chemotherapy (BCG in 2 cases). Seventeen (63%) patients had multiple (2.3) marker lesions, all less than 10mm. Starting 14 days after TUR, 6 instillations of gemcitabine were given at weekly intervals. Gemcitabine, diluted in 50 cc 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, 14-21 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. Complete response (CR) was defined as negative cytology, cystoscopy and biopsy. Partial response (PR) was defined as a reduction in number of multiple lesions. Local and systemic toxicity was investigated at weekly intervals. Routine laboratory tests were carried every 4 weeks. Patients achieving a complete response received monthly maintenance up to one year and were followed every 3 months by cytology and cystoscopy. 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 against TCCB. A CR rate up to 33% has been obtained.