title: Continuous infusion, intravesical doxorubicin for the treatment of regionally advanced bladder cancer: a phase I-II trial.
abstract: Patients with regionally advanced bladder cancer not considered candidates for definitive surgical intervention underwent continuous antegrade infusion of doxorubicin by percutaneous nephrostomy tube. Doxorubicin was administered for 7 consecutive days at a rate designed to achieve target urinary concentrations (range 5-80 micrograms/ml). Urine and serum concentrations of doxorubicin were monitored daily. Toxicity was assessed by serial renal scans, antegrade nephrostograms, blood counts, and serum chemistries. Patients were restaged after three cycles of therapy. In all, 23 cycles, constituting 156 days of therapy, were administered to 10 patients. Target urinary drug levels were achieved during all cycles. Total doxorubicin dose ranged from 125 to 2,500 mg. No systemic (neutropenia or myocardial dysfunction) or regional toxicity (extravasation, sepsis, stricture) was noted. Five of 10 patients tolerated the planned three treatment cycles. Poor performance status (PS, Eastern Cooperative Oncology Group: ECOG 3) strongly correlated with treatment intolerance and early death from disease. After three cycles of therapy, 2 of 5 evaluable patients had stable disease, I had radiographic partial response (PR) with a biopsy demonstrating extensive tumor necrosis, I had no identifiable tumor at the time of restaging transurethral resection of bladder tumor (TURBT), and a final patient with upper and lower tract carcinoma in situ (CIS) was cytologically staged NED. (no evidence of disease). These findings demonstrate the feasibility and low toxicity of this approach.
authors.affiliation: Department of Urology, University of Iowa, Iowa City 52242-1089, USA.
authors.forename: W A
authors.initials: WA
authors.lastname: See
authors.forename: R
authors.initials: R
authors.lastname: Dreicer
authors.forename: P K
authors.initials: PK
authors.lastname: Forest
authors.forename: C
authors.initials: C
authors.lastname: Riggs
mesh_terms: D000283:Administration, Intravesical; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use* / Q000652:urine; D001706:Biopsy; D002278:Carcinoma in Situ / Q000188:drug therapy; D002423:Cause of Death; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use* / Q000652:urine; D016903:Drug Monitoring; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007267:Injections; D007440:Intubation / Q000295:instrumentation; D008297:Male; D009336:Necrosis; D009367:Neoplasm Staging; D009403:Nephrostomy, Percutaneous / Q000295:instrumentation; D012074:Remission Induction; D012449:Safety; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin