PROPHYLACTIC INTRAVESICAL INSTILLATION CHEMOTHERAPY AGAINST RECURRENCE AFTER A TRANSURETHRAL RESECTION OF SUPERFICIAL BLADDER-CANCER - A RANDOMIZED CONTROLLED TRIAL OF DOXORUBICIN PLUS VERAPAMIL VERSUS DOXORUBICIN ALONE

Purpose: We investigated whether verapamil (VR), a known chemosensitiz ing agent of P-glycoprotein-mediated multidrug resistance, could enhan ce the preventative effect of doxorubicin (Adriamycin, ADM) on both in travesical recurrence and disease progression, after transurethral res ection (TUR) of superficial bladder cancer. Methods: The patients were randomized into two groups: one group received an intravesical instil lation of ADM (30 mg) plus VR (15 mg) after TUR of superficial bladder cancer (19 times over 1 year), and the other group received ADM alone on the same treatment schedule. The nonrecurrence rate, the incidence of disease progression at the first recurrence and the side effects w ere compared over a median follow-up of 38.5 months. Results: Of the 2 26 patients registered, 157 were evaluable. No significant differences were observed in the patients' characteristics between the two groups . Although the incidence of disease progression at the first recurrenc e was not significantly different between the two groups, the ADM plus VR instillation group did show a significantly higher nonrecurrence r ate than the ADM-only instillation group, and such significance persis ted even when any possible bias was allowed for in a multivariate anal ysis. In terms of side effects, the incidence and severity of bladder irritation symptoms were not significantly different between the two g roups. Conclusions: Intravesical instillation chemotherapy with ADM pl us VR was found to have a significantly greater beneficial effect than with ADM alone for preventing recurrence after TUR of superficial bla dder cancer.