Bladder damage in mice after single and repeated intravesical instillations of mitomycin C or doxorubicin

Functional and histological damage after intravesical administration of mitomycin C or doxorubicin were studied in mouse bladders. Dosing schedules were based on those commonly used in the clinic, and bladder function was assessed from changes in urination frequency. Repeated weekly instillations of 1 mg./ml. mitomycin C induced a transient three-fold increase in Frequency Index (FI) with recovery to control levels within 3 weeks. Weekly instillations of 6 mg./ml. doxorubicin also resulted in a three-fold increase in FI, but lower doses produced only minimal changes. There was, again, full recovery within 3 weeks. Our experiments indicate that repeated intravesical instillations of mitomycin C or doxorubicin are well tolerated, with rapid recovery from functional damage within a few weeks of cessation of therapy. There was significantly less damage after repeated instillations of clinically relevant doses of doxorubicin than mitomycin C.