Muscle-invading bladder cancer, RTOG Protocol 99–06: Initial report of a phase I/II trial of selective bladder-conservation employing TURBT, accelerated irradiation sensitized with cisplatin and paclitaxel followed by adjuvant cisplatin and gemcitabine chemotherapy

Abstract

4506 Background: To examine the protocol completion and response rate of cisplatin plus paclitaxel and twice-daily irradiation following TURBT to preserve the bladder and to determine the tolerance of 4 cycles of chemotherapy. Methods: Induction treatment involved 13 days of twice-daily irradiation, cisplatin (20 mg/m2) on the first two days of each week, and paclitaxel (50 mg/m2) on the first day of each week. Three weeks following induction, patients were cystoscopically evaluated for residual disease. Those whose tumor-site biopsies showed no disease completed consolidation chemoradiation. Patients with residual tumor went on to cystectomy. Following consolidation or cystectomy patients were to complete 4 cycles of cisplatin and gemcitabine chemotherapy. Results: Fifty patients, staged T2-T4a N0 M0 were entered onto the treatment regimen. Forty-seven patients were evaluable for the primary endpoint of treatment completion. Clinical T-stages were: T2 (90%), T3a (8%) and T3b (2%). Median followup was 30 months. Thirty-four (72%) of the 47 evaluable patients completed all treatment per protocol or with an acceptable variation. The complete response (CR) rate after induction therapy was 87%. Grade 3 or 4 toxicity was observed in 32% of patients (induction and consolidation), and in 74% during adjuvant chemotherapy. Twenty-nine percent experienced Grade 4 toxicities during followup, mainly hematologic, and one Grade 5. Conclusions: Although we did not achieve a 90% protocol completion rate with this treatment regimen, it did result in a CR rate of 87%. These early outcomes are encouraging in that this protocol regimen, the first to include adjuvant treatment with cisplatin and gemcitabine may be effective in cancer control. This trial was supported by NCI U10 CA21661 and Eli Lilly & Co.