A Phase 1 Trial of Intravesical Cabazitaxel, Gemcitabine, and Cisplatin for the Treatment of Non-muscle Invasive BCG Unresponsive or Recurrent/Relapsing Urothelial Carcinoma of the Bladder.

PURPOSE: For patients with BCG unresponsive or recurrent/relapsing non-muscle invasive bladder cancer (NMIBC), multi-agent intravesical trials have been limited. The goal of this study was to investigate the safety of intravesical cabazitaxel, gemcitabine, and cisplatin (CGC) in the salvage setting. MATERIALS AND METHODS: This was a dose-escalation, drug-escalation trial for patients with BCG unresponsive or recurrent/relapsing NMIBC who declined or were ineligible for radical cystectomy. All patients underwent a 6-week induction regimen of sequentially administered cabazitaxel, gemcitabine and cisplatin. Complete response was defined as no cancer on post-induction TURBT and negative urine cytology, while partial response allowed for positive cytology. Responders continued with maintenance cabazitaxel and gemcitabine monthly for the first year and bimonthly for the second year. RESULTS: Eighteen patients were enrolled. Mean age was 71 years, median follow-up was 27.8 months (16.3 - 46.9), and mean number of previous rounds of intravesical therapies prior to trial enrollment was 3.7. Nine patients (50%) had received intravesical chemotherapy after BCG, and seven (39%) were previously treated in a Phase I clinical trial setting. At enrollment, 6/18 (33%) subjects had T1 disease, and 13/18 (72%) had CIS. There were no dose-limiting toxicities. Initial partial and complete response rates were 94% and 89%, respectively. At one year, recurrence-free survival (RFS) was 0.83 (0.57 - 0.94), and at two years estimated RFS was 0.64 (0.32, 0.84). CONCLUSIONS: In this high risk and highly pre-treated cohort of BCG unresponsive or recurrent/relapsing NMIBC subjects, combination intravesical cabazitaxel, gemcitabine, and cisplatin was a well-tolerated and potentially effective regimen.