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) administered as protracted intravenous infusion (PVI) during hyperfractionated radiotherapy (HFRT) administered with organ-sparing intent to patients with infiltrating transitional cell carcinoma of the bladder (TCCB). METHODS: 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 MTDs were reached. Treatment efficacy was also evaluated, in terms of complete response (CR) rates and cystectomy free, disease free, and overall survival. RESULTS: Combined treatment was well tolerated. The recommended doses for Phase II studies of PVI chemotherapy and radiotherapy for patients with invasive bladder carcinoma are CDDP 5 mg/m2/day and 5-FU 220 mg/m2/day. Twenty-four patients were evaluable for response: 21 (87.5%) had CR and 3 PR. After a median follow-up of 31 months (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 recurrence successfully treated with endovesical therapy and 1 had distant metastases. Three patients were submitted to cystectomy, one for superficial recurrence and hematuria and two for invasive bladder recurrence. CONCLUSIONS: This study defines the MTDs of CDDP and 5-FU concomitantly administered with hyperfractionated radiotherapy. The low toxicity observed and the high CRs and bladder preservation rates deserve further study.

[Role of computerized tomography in bladder carcinoma treated with simultaneous combined radiotherapy and chemotherapy]. / Ruolo della Tomografia Computerizzata nel carcinoma vescicale sottoposto a radio e chemioterapia contemporanee associate.

We report on the pneumocystography-CT follow-up of locally aggressive bladder carcinoma patients treated with combined and simultaneous irradiation and chemotherapy. Particular attention was paid to assess residual thickening of the wall involved by the tumor, which is the most critical parameter to discriminate a persistent from a resolved condition. We examined 16 patients (mean age: 66.5 years) with histologically locally advanced urinary bladder cancer staged T2-T3. All patients underwent the first CT exam of the bladder with the pneumocystography technique before therapy, for disease staging, another exam after chemotherapy and a third one after simultaneous irradiation and chemotherapy. The endoluminal mass completely regressed in all cases, with normal endoscopic findings. In 9 of 16 cases, the bladder wall was thickened in the tumor site, with normal mucosal surface. The histology of bioptic specimens obtained during cystoscopy showed a high frequency of phlogistic reactions from foreign bodies, corresponding to the bladder wall thickening seen on CT images. We conclude that, in extensive neoplastic bladder wall involvement, therapy-induced histologic regressive phenomena can cause a granulomatous reaction in the bladder wall, thus thickening it, which is the most frequent sign in these cases but that, in our experience, was never associated with tumor invasion. This should be always considered in the CT studies performed after this kind of combined treatment.