Randomized phase III trial comparing adjuvant paclitaxel/gemcitabine/cisplatin (PGC) to observation in patients with resected invasive bladder cancer: Results of the Spanish Oncology Genitourinary Group (SOGUG) 99/01 study.

LBA4518 Background: Approximately half of patients with resected invasive bladder cancer will die within the first three years after surgery due to disease relapse, most of the recurrences being systemic. We have studied in a randomized phase III trial the role of 4 courses of the PGC triplet as compared to observation in this clinical setting. Methods: Eligibility criteria included: (1) resected high-risk muscle invasive bladder carcinoma (pT3-4 and/or pN+), (2) ECOG PS 0-1, (3) adequate renal function (CrCl > 50 ml/min), (4) ≤ 8 weeks post-cystectomy, (5) no relevant co-morbidities, and (6) signed informed consent. Eligible patients were assigned to observation or 4 courses of PGC (P 80 mg/m 2 d1 and 8, G 1000 mg/m 2 d1 and 8 and C 70 mg/m 2 d1) q21 days. The primary objective was overall survival (OS). Results: The study was open in July 2000 and prematurely closed due to poor recruitment in July 2007, with 142 patients randomized (74 to observation and to 68 to PGC treatment). Baseline characteristics were well balanced among study arms. Median age was 63 yrs, pT3-4N0: 44%, anyTpN+:56%, PS 0: 59%, median time cystectomy-randomization: 48 days (14-91). In the PGC arm 76% of pts completed all 4 courses of therapy. Main Gr 3-4 toxicities were neutropenia 41%, febrile neutropenia 8%, thrombocytopenia 14%, anemia 5%, fatigue 14%, alopecia 10%, vomiting 8%, renal 5%. There was one toxic death (sepsis). At a median follow up of 30 months (range 1-95), 69 patients have died (45 in control arm and 24 in PGC arm). OS (ITT population) was significantly prolonged in the PCG arm (median NR; 5yr OS: 60%) compared to observation (median 26m; 5yr OS: 31%) (p<0.0009). DFS (p<0.0001), TTP (p<0.0001) and disease specific survival (p<0.0002) were also superior in the PGC arm. Conclusions: The results of this study strongly suggest that adjuvant PGC improves OS and DFS following cystectomy in high risk invasive bladder cancer. As the study was prematurely closed, the power for firm conclusions is however limited. [Table: see text]