Heat-activated intravenous liposomal doxorubicin combined with mitomycin C hyperthermic intravesical chemotherapy (HIVEC) for treatment of bladder cancer

PURPOSE: ) combined with mitomycin C (MMC) hyperthermic intravesical chemotherapy (HIVEC) as a potential treatment for non-muscle invasive bladder cancer. MATERIALS AND METHODS: Four healthy swine received a 30-minute intravenous infusion of LTLD in combination with HIVEC, consisting of one hour of warm MMC bladder recirculation. Full-thickness bladder wall specimens were surgically resected within 30 min of HIVEC completion for histologic analysis and assessment of doxorubicin (DOX) intrinsic fluorescence in cross sections. DOX and MMC concentrations were also measured in bladder specimens and in serial blood samples up to 4 h by LC/MS. Swine were monitored for 28 days for signs of toxicity and were weighed weekly. Complete blood counts were performed at 4 h and 28 days. Cystoscopy was performed at 28 days, and bladder tissue was collected for histology and quantification of drug concentrations. RESULTS: were 16.4 ± 3.46 µg/mL and 23.2 ± 5.50 µg/mL · h, respectively. MMC was not detected in the bladder wall or blood above the lower limit of detection (20 ng/mL). The treatment was well tolerated, with no treatment-related adverse events and no weight loss during the 28-day observation. On day 28, cystoscopy demonstrated normal-appearing bladder lumen, and some vacuolated cells were observed on bladder wall histology. CONCLUSIONS: Intravenous LTLD combined with MMC HIVEC was feasible and well tolerated in swine.