Clinical trial of high dose hyperthermic intravesical mitomycin C for intermediate and high-risk non-muscle invasive bladder cancer during BCG shortage

Purpose: Intravesical Bacillus Calmette-Guerin (BCG) is the gold standard for intermediate and high-risk non-muscle invasive bladder cancer (NMIBC), but availability is limited by global shortages. We present the first North American clinical experience using intravesical hyperthermia (HIVEC) with high-dose mitomycin C (MMC) during BCG shortage. Materials and methods: Single arm intermediate size expanded access protocol for high dose HIVEC MMC in patients with intermediate and high-risk NMIBC during BCG shortage. Patients received 120 mg intravesical MMC using the Combat BRS to achieve 43 degrees C HIVEC. Primary outcome was a safety assessment of adverse events, with recurrence-free survival and a descriptive analysis of hematologic impacts as secondary outcomes. Results: Fourteen patients were treated from May 2019 to June 2020, 4 (29%) intermediate and 10 (71%) high risk. The cohort is heavily pretreated, only 2 (14%) BCG naive and median 6 BCG instillations (IQR 5.25, 8.25), with median 3.5 recurrences per patient (IQR 1.00, 5.25) 67% with >1 per year. Patients underwent a median 6 instillations (IQR 3.25, 9.25) which were well tolerated in 11/14 (79%). Seven patients (50%) experienced 10 adverse events, all grades 1 or 2. Most common was MMC allergy (4/14, 29%), followed by bladder spasm (3/14, 21%). Two had recurrences at median 11 months follow up, but both discontinued HIVEC after only 2 treatments. Conclusions: High dose MMC HIVEC is a safe and well-tolerated substitute for BCG during global shortages. The higher rate of systemic effects implies increased drug delivery, which may improve efficacy. (C) 2020 Elsevier Inc. All rights reserved.