Multi-institutional analysis of sequential intravesical gemcitabine and mitomycin C chemotherapy for non–muscle invasive bladder cancer

Abstract

Objective Apart from cystectomy, few treatment options exist for the management of bacillus Calmette-Guerin refractory non–muscle invasive bladder cancer (NMIBC). We report a multi-institutional experience with sequential intravesical combination chemotherapy using gemcitabine and mitomycin C (MMC) for NMIBC in the treatment of high-risk patients. Methods We performed a retrospective review of patients who received 6 weekly treatments with sequential intravesical gemcitabine (1 g) and MMC (40 mg) chemotherapy for NMIBC. Gemcitabine was administered first and retained for 90 minutes and then drained. MMC was then administered directly after and retained for an additional 90 minutes. Forty-seven patients received treatment from 3 academic tertiary referral centers between 2000 and 2010. Results Forty-seven patients (median age 70, range 32–85; 36 males, 11 females) who previously failed a median of 2 intravesical treatments were reviewed. Complete response, 1-year, and 2-year recurrence-free survival rates for all patients were 68%, 48%, and 38%, respectively. Median recurrence-free survival for all patients was 9 months (range 1–80). Fourteen of 47 patients (30%) remained free of recurrence with a median time to follow-up of 26 months (range 6–80 mo). Ten patients required cystectomy. Conclusion Sequential intravesical combination chemotherapy using gemcitabine and MMC appears to be a useful treatment for patients with high-grade NMIBC as well as those with prior bacillus Calmette-Guerin failure. Further prospective studies are warranted.

Current clinical trials in non–muscle invasive bladder cancer

“…[31] Similarly, a multi-institutional retrospective study of high-risk NMIBC patients treated with sequential intravesical gemcitabine followed by MMC demonstrated recurrence-free survival rates of 50% at 12 months. [32] Given the encouraging outcomes, a phase I trial is underway to evaluate the safety of various combinations of chemotherapeutic agents, such as cabazitaxel, gemcitabine, and cisplatin when given intravesically in patients with BCG-unresponsive NMIBC.…”

New developments in the management of nonmuscle invasive bladder cancer

“…(33) A multi-institutional analysis for sequential intravesical Gemcitabine with Mitomycin C found that patients with high-grade NMIBC or BCG refractory disease had a 2 year recurrence free survival of nearly 40%. (34) These studies lend further evidence that salvage protocols utilizing Gemcitabine in this setting show promise.…”

Consensus statement on best practice management regarding the use of intravesical immunotherapy with BCG for bladder cancer

“…87,88 Sequential gemcitabine-mitomycin C in 47 patients with highrisk disease, primarily after BCG failure, resulted in a complete response in 68% of patients with 1year and 2year diseasefree survival of 48% and 38%, respectively. 89 Alternatively, sequenced g emcitabine-docetaxel in 45 patients with highrisk disease yielded a complete response rate of 66%, as well as 1year and 2year recurrencefree survival of 54% and 34%, respectively. 90 Reassuringly, although the cystec tomy rate for both regimens was around 20%, metastasis was rarely reported.…”