Intravesical gemcitabine in superficial bladder tumours preliminary results of a phase I-II study

INTRODUCTION & OBJECTIVES: Gemcttabme is a pro-drug requmng intracellular phosphorylation by deoxycytidine kinase to be activated. Preliminary experiences. suggesting the activtty and the good tolerability of the drug on superficial transitional cell carcinoma of the bladder (TCCB) when administered by intravesical route, have been recently published. The mm of the present study was to evaluate the ablative efftcacy of weekly intravesical instillations of gemcitabine against paptllary marker lesions left after TUR of superficial TCCB. The scientific background and the ethical acceptability of thts approach have been balidated by the European Organization for Research and Treatment ot Cancer Urological Group. MATERIAL & METHODS: Twelve patients. affected by recurrent multiple superficial TCCB (Ta-Tl, Gl-G2), were treated with intravesical gematabine after a transurethral resection (TUR) during which 1 to 3 papillary marker lesions (5-15 mm in diameter) were left unresected. High-grade (G3) tumours and Tis were excluded. Nine patients have been previously treated with mtravesical chemotherapy. Starting I4 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 my and 2000 mg in 4. 5, and 4 patients respectively. The patients, 14-21 days after the last instillation. were submitted to cytology. cystoscopq and TUR or cold cup biopsy of every suspicious lesion and at the sites ofthe marker tomours. Complete response (CR) wa\ 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 out every 4 weeks. Patients achieving a complete response received monthly maintenance and were followed every 3 months by cytology and cystoscopy. RESULTS: Three patients are still under treatment and will bc soon evaluated. Of 9 patients, 2 (22%) achieved a complete response. Particularly, CRs were detected in patients treated with 500 and 2000 mg. A PR was obtained in 2 (22%) more patients. No progression m either ti or T-category was detected. The two patients with CR are disease-free respectively at 8 and 3 months. Local tolerabtlity was excellent. No systemic side effects were detected. Updated data will be presented. CONCLUSIONS: Our experience. although preliminary. shows the excellent tolerability and the potential efftcacy of gemcitabine when administered intravealcally for therapy of superficial TCCB. The CR rate is 22%. This is apparently lower than that obtained wtth conventional drugs such as BCti, epirubicin or mitomycin C. but no dxect comparison can be made since only 4 patient? have been actually treated at the higher dose. PR even if taken into account, ts of uncertam prognostic significance.