Presentation Authors: G Joel DeCastro*, Christopher Anderson, Jamie Pak, New York, NY, Max Kates, Baltimore, MD, Bridget Buckley-Matura, New York, NY, Wilson Sui, Nashville, TN, Shing M Lee, New York, NY, Dara Holder, Madison, WI, Renu Virk, Charles Drake, Cory Abate-Shen, James McKiernan, New York, NY
Introduction: For patients with non-muscle invasive bladder cancer (NMIBC) unresponsive to Bacille Calmette-Guerin (BCG), multi-agent intravesical trials have been limited. The goal of this study was to investigate the safety of intravesical chemotherapy consisting of sequential cabazitaxel, gemcitabine, and cisplatin (CGC) in the salvage setting. Funding support for the trial was provided by Sanofi Genzyme.
Methods: This was a dose-escalation, drug-escalation trial enrolling patients with BCG refractory or recurrent high-risk NMIBC who refused or were ineligible for radical cystectomy. All patients underwent a pre-treatment transurethral resection of bladder tumor (TURBT) and a 6-week regimen of intravesical chemotherapy, with each drug instilled weekly except for cisplatin, which was given every other week. Complete response was defined as no evidence of cancer on post-induction TURBT and negative urine cytology; these patients proceeded with monthly and bimonthly maintenance therapy in the first and second years, respectively, for a total of 24 months. Toxicity was categorized according to Common Terminology for Adverse Events v4.
Results: Eighteen patients were enrolled, of whom four were female. Mean age was 71 years, median follow-up was 13 months, and mean number of previous rounds of intravesical therapies prior to enrollment was 3.7. All patients had previously received at least two prior induction cycles of BCG, and 17/18 patients (94%) were BCG refractory. Nine patients (50%) previously received intravesical chemotherapy after BCG (+/- IFN), seven (39%) of whom were previously treated in a Phase I clinical trial setting. All patients had high grade disease at enrollment, with 9/18 (50%) patients with T1 and 12/18 (67%) patients with CIS. There were no dose-limiting toxicities. Initial complete response rate was 94%. At last follow up, four patients (22%) recurred at median time of 9.5 months, though two patients recurred in the prostatic urethra (both of whom had high grade disease in the prostatic urethra immediately prior to enrollment). Three patients (17%) underwent cystectomy at median time of 12 months. Fourteen patients (78%) remained disease-free at last follow up.
Conclusions: Combination intravesical cabazitaxel, gemcitabine, and cisplatin appears to be a well-tolerated, promising salvage chemotherapy regimen for the treatment of BCG unresponsive NMIBC.
Source of Funding: Sanofi Genzyme