Safety evaluation of sequential mitomycin and bacillus calmette-guerin treatment versus bacillus calmette-guerin monotherapy in patients with high risk non-muscle invasive bladder cancer: mitobcg study(eudract number 2017-004540-37)preliminary results

INTRODUCTION AND OBJECTIVE: Aim of our study was to evaluate safety of sequential Mitomycin and Bacillus Calmette-Guérin (BCG) treatment versus BCG monotherapy in patients with High risk Non-Muscle Invasive Bladder Cancer. METHODS: MITO-BCG is an open-label phase 4 study designed to evaluate the efficacy and safety of the sequential MMC and BCG combination treatment in patients with high-risk NMIBC. Eligibility criteria are: males with an High risk NMIBC, age between 40 and 75, ability of consent. Patients are randomized in two groups: one with BCG induction treatment according to the standard protocol, the second one receives BCG treatment adding a 40 mg mitomycin instillation the day before. Response is assessed performing cystoscopy and urine citology every 12 weeks for 2 years. A CT scan will be performed every year. Adverse events (AEs) are monitored until 2 years after the end of the treatment (90 days for serious and of clinical interest AEs) and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Primary end point is recurrence rate; secondary end point is overall toxicity. Exploratory end points include assessments of HrQoL using voiding diary and IPSS, PUF, NIH-CPSI questionnaires. Enrollment will continue till 200 patients are included. RESULTS: Since March 2019, 36 patients were enrolled with a median age of 67(IQR 59/73).Overall, 42% patients were randomized in the sequential combination therapy group and 48% in the monotherapy group with BCG.After treatment, six patients experienced AEs, 3 (50%) in the combination therapy group and 3 (50%) in the BCG group. Five AEs (urethral sub-stenosis, fever, asthenia, fainting, cystitis) were CTCAE grade I.Only one AE was a grade III, acute epididymo-orchitis with abscess requiring orchiectomy in the monotherapy BCG group (Table). No significative differences were found between the groups (Table). CONCLUSIONS: Preliminary results (MITOBCG study) support that sequential combination therapy with mytomicin and BCG is a safety treatment in high risk NMIBC.