Abstract
4590 Background: Efficacy of second-line treatment after cisplatinum failure in patients (pts) with advanced urothelial cancer is limited. Based on encouraging preclinical data and results from several phase I trials in solid cancers, we evaluated the safety and efficacy of the combination of paclitaxel and RAD001 (everolimus) in these pts. Methods: In this single-arm, multicenter phase II trial, pts failing prior cisplatinum based combination treatment for advanced urothelial cancer were treated with paclitaxel (175 mg/m² i.v., three-weekly) and the mTOR-inhibitor RAD001 (10 mg p.o., once daily). Pts were treated until tumor progression by RECIST criteria or until a maximum of 6 cycles was completed. A one-stage design was used to evaluate the overall response rate (ORR) as primary endpoint. Results: 27 pts (18 men, 9 women; median age 63 (35-76) years; ECOG ≥ 1: 11/27pts, hepatic metastases: 10 pts, Hb<10 g/dl: 8 pts; upper urinary tract: 9 pts, lower urinary tract 15 pts, both: 3 pts) were enrolled between 07/09 and 12/11. As of 01/12, 19 pts are evaluable for the primary endpoint and the toxicity profile (6 pts still on treatment, 1 patient has withdrawn consent). Main toxicities (all CTCAE grades) were anemia (10/19 pts), leucopenia (8/19 pts), and neuropathy (9/19 pts). Grade III/IV toxicities were anemia (4/19 pts) and leucopenia (4/19 pts). No treatment related deaths were observed. Median number of cycles was 4 (1-6). Complete remission (CR) and partial remission (PR) was observed in 0/19 and 3/19 pts, respectively (ORR 16%). Stable disease (SD) was observed in 10/19 pts. Median time-to-progression (TTP) was 2.7 months (95% confidence interval [CI] 1.6 – 4.4), median overall survival (OS) was 6.5 (CI 4.5 – 9.2) months. Conclusions: Frequency and severity of toxicities were acceptable. Using the combination of RAD001 and paclitaxel as second-line treatment for advanced urothelial cancer after cisplatinum-failure, response rates and survival times comparable to vinflunine were observed.
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