CONTINUOUS-INFUSION, INTRAVESICAL DOXORUBICIN FOR THE TREATMENT OF REGIONALLY ADVANCED BLADDER-CANCER - A PHASE I-II TRIAL

Patients with regionally advanced bladder cancer not considered candid ates for definitive surgical intervention underwent continuous antegra de infusion of doxorubicin by percutaneous nephrostomy tube. Doxorubic in was administered for 7 consecutive days at a rate designed to achie ve target urinary concentrations (range 5-80 mu g/ml). Urine and serum concentrations of doxorubicin were monitored daily. Toxicity was asse ssed by serial renal scans, antegrade nephrostograms, blood counts, an d serum chemistries. Patients were restaged after three cycles of ther apy. In all, 23 cycles, constituting 156 days of therapy, were adminis tered to 10 patients. Target urinary drug levels were achieved during all cycles. Total doxorubicin dose ranged from 125 to 2,500 mg. No sys temic (neutropenia or myocardial dysfunction) or regional toxicity (ex travasation, sepsis, stricture) was noted. Five of 10 patients tolerat ed the planned three treatment cycles. Poor performance status (PS, Ea stern Cooperative Oncology Group: ECOG 3) strongly correlated with tre atment intolerance and early death from disease. After three cycles of therapy, 2 of 5 evaluable patients had stable disease, 1 had radiogra phic partial response (PR) with a biopsy demonstrating extensive tumor necrosis, 1 had no identifiable tumor at the time of restaging transu rethral resection of bladder tumor (TURBT), and a final patient with u pper and lower tract carcinoma in situ (CIS) was cytologically staged NED. (no evidence of disease). These findings demonstrate the feasibil ity and low toxicity of this approach.