Neoadjuvant Short-term Intensive Intravesical Mitomycin C Regimen Compared with Weekly Schedule for Low-grade Recurrent Non-muscle-invasive Bladder Cancer: Preliminary Results of a Randomised Phase 2 Study

Background: The schedule for intravesical chemotherapy administration has not been definitively established in patients with low-grade recurrent non-muscle-invasive bladder cancer (NMIBC). Objective: To assess both the feasibility and the efficacy of a short-term intensive schedule of neoadjuvant intravesical chemotherapy in patients with recurrent NMIBC. Design, setting, and participants: A randomised phase 2 clinical study included 54 patients with recurrent NMIBC who were submitted to neoadjuvant chemotherapy intravesical instillations according to two different timing schedules. The study was performed at a tertiary care referral centre. Intervention: Intravesical mitomycin C (MMC) 40 mg/40 ml was administered according to a schedule of either one instillation per week for 6 wk (group 1) or three instillations per week for 2 wk (group 2) prior to transurethral resection (TUR). Outcome measurements and statistical analysis: Local and systemic toxicity were investigated using the US National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.4.0 questionnaire at each instillation and the SF-36 questionnaire at randomisation and before TUR. A video-recorded cystoscopy and TUR were performed within 14 d after treatment completion. Results and limitations: Groups 1 and 2 each were assigned 27 cases. Two patients (7.4%) in group 2 could not complete the scheduled treatment because of severe lower urinary tract symptoms. No statistically significant difference in SF-36 domain score was documented pre- and post-treatment between groups. Likewise, no statistically significant difference in treatment-related toxicity according to the CTCAE v. 4 questionnaire was registered. Twelve patients (44.4%) in group 1 and 19 patients (70.4%) in group 2 (p = 0.04) had complete tumour response. The small number of patients included represents the main limitation of the study. Conclusions: The intensive short-term schedule of neoadjuvant chemotherapy is safe and without additional toxicity compared with the weekly regimen. The increased ablative effect may be explained by the improved adherence of the scheduled timing to the duplication rate of tumour cells. (c) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.