Concurrent gemcitabine (GEM) and radiotherapy (XRT) as organ-sparing treatment for muscle-infiltrating bladder cancer (MIBC): Preliminary results of a patient-based cumulative analysis of seven phase I-II trials.

Abstract

306 Background: GEM is a highly effective radiosensitiser and has been combined with XRT in MIBC after transurethral resection (TUR) to achieve bladder preservation. Several phase I-II trials confirmed that concurrent GEM and XRT is a feasible treatment able to achieve good disease control and a high rate of organ preservation. We performed a patient-based cumulative analysis of the published trials with concurrent GEM/XRT in MIBC. Methods: Primary data for patients (pts) enrolled in all published studies on GEM/XRT were provided from the institutions. Results: A total of 190 pts were treated in seven phase I-II GEM/XRT trials. The median age was 70 yrs (range 42-87 yrs). The histology was pure transitional in 79% and mixed with squamous features in 21% of the cases. Clinical stage was T2 in 70%, T3 in 21%, and T4 in 8% of the cases, respectively. After TUR, pts received a median XRT dose of 55.5 Gy (range 45-64 Gy) with standard and hypo-fractionated regimes used in 68% and 32% of the cases, respectively. GEM was administered on a weekly or twice-weekly basis, with doses ranging from 10 mg/sqm to 500 mg/sqm; a concurrent administration of cisplatin was planned in 38 pts (20%). Grade ≥ 3 acute and late urinary toxicities were recorded in 7 (4%) and 5 (3%) pts, while grade ≥ 3 acute and late intestinal toxicities were recorded in 20 (10%) and 1 (0.5%) pts, respectively. The complete remission rate was 93.3%. Thirty-six pts (18.9%) experienced a bladder recurrence with 14 pts undergoing cystectomy. The 3- and 5-year survival rates calculated by Kaplan-Meier methods are reported in the table. Conclusions: From this pooled analysis of the clinical outcomes of the pts enrolled in phase I-II studies it appears that GEM/XRT is a treatment with mild toxicity profile, able to achieve a high rate of bladder preservation and producing favorable outcomes compared to other published series for organ-sparing therapy for MIBC. Prospective studies are ongoing to confirm these findings. [Table: see text]