Intravesical gemcitabine for treatment of superficial bladder cancer not responding to Bacillus Calmette-Guérin vaccine

Abstract

Intravesical Bacillus Calmette-Guerin (BCG) vaccine is the mainstay of treatment and prophylaxis in superficial bladder cancer (SBC) as it reduces tumor recurrence and disease progression. About one-third of patients do not respond to BCG. The aim of this study was to determine the efficacy of intravesical gemcitabine in patients with BCG-refractory SBC. Twenty three patients with SBC; TaG3, T1G2-G3 or carcinoma in situ (CIS), refractory (after at least 2 courses of intravesical BCG) or intolerant to intravesical BCG therapy were included. Two weeks after complete tumor resection, patients received intravesical gemcitabine twice weekly at a dose of 2.000 mg/100 ml normal saline for 6 consecutive weeks. Two months after the last dose, recurrence-free patients underwent cystoscopy, urinary cytology and 6 random bladder biopsies. Thereafter, patients were evaluated by the same measures every 3 months, as long as there was no recurrence. Patients with complete response (negative cytology and random biopsies) at the first follow-up cystoscopy received a similar maintenance dose once weekly for another 6 weeks. Twenty one patients completed the study: 15 males and 6 females with a mean age of 48.1 (38–72) years. The follow-up was 15 months (range 2–19 months). Thirteen (61.9%) patients were recurrence-free after a mean of 17 months. Superficial recurrences were detected in 6 (28.6%) patients and progression by stage in 2 patients (9.5%). During follow-up, 8 patients had tumor recurrences and 2 had progression to a higher stage. The median recurrence-free time was 14.7 months (5–19 months). The drug was well tolerated and side-effects were mild in all patients, except two: one had easily controlled hematuria and the other had leucopenia. In properly selected patients, gemcitabine seems to be a promising option in the management of high-risk BCG-refractory SBC, especially in those who refuse or are unfit for cystectomy. Long-term efficacy and the role of maintenance therapy have to be properly studied.