COMBINED TREATMENT OF INVASIVE BLADDER-CARCINOMA WITH TRANSURETHRAL RESECTION, INDUCTION CHEMOTHERAPY, AND RADICAL RADIOTHERAPY PLUS CONCOMITANT PROTRACTED INFUSION OF CISPLATIN AND 5-FLUOROURACIL - A PHASE-I STUDY

BACKGROUND, The aim of this study was to define the maximum tolerated doses (MTDs) of cisplatin (CDDP) and 5-fluorouracil (5-FU) administere d as protracted intravenous infusion (PVI) during hyperfractionated ra diotherapy (HFRT) administered with organ-sparing intent to patients w ith infiltrating transitional cell carcinoma of the bladder (TCCB), ME THODS, Twenty-five patients with T2-T4aNXM0 TCCB were enrolled in this study. After a complete transurethral resection, bladder mapping, and two cycles of induction chemotherapy, patients were submitted to HFRT and CDDP + 5-FU as concomitant PVI at escalating dose levels until MT Ds were reached. Treatment efficacy was also evaluated, in terms of co mplete response (CR) rates and cystectomy free, disease free, and over all survival. RESULTS, Combined treatment was well tolerated. The reco mmended doses for Phase II studies of PVI chemotherapy and radiotherap y for patients with invasive bladder carcinoma are CDDP 5 mg/m(2)/day and 5-FU 220 mg/m(2)/day. Twenty-four patients were evaluable for resp onse: 21 (87.5%) had CR and 3 PR. After a median follow-up of 31 month s (range, 11-49 months), 18 of 21 patients with CRs (86%) were alive: 15 (71.4%) had tumor free bladder, of whom 3 had superficial recurrenc e successfully treated with endovesical therapy and 1 had distant meta stases. Three patients were submitted to cystectomy, one for superfici al recurrence and hematuria and two for invasive bladder recurrence. C ONCLUSIONS, This study defines the MTDs of CDDP and 5-FU concomitantly administered with hyperfractionated radiotherapy. The low toxicity ob served and the high CRs and bladder preservation rates deserve further study. (C) 1997 American Cancer Society.