Tan, Wei Phin

259 Background: Vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) are produced by bladder cancer cell lines in vitro and expressed in human tumor tissues. Preclinical studies have also shown that bladder cancer cell lines express VEGF receptor 1 and 2 on their surface membrane. Pazopanib is a vascular endothelial receptor tyrosine kinase inhibitor with anti-angiogenesis and antitumor activity in several preclinical models. A two-stage phase II study was conducted to assess the activity and toxicity profile of pazopanib administered to patients with metastatic, urothelial carcinoma. Methods: Patients with one prior systemic therapy for recurrent, metastatic urothelial carcinoma were eligible. Patients received pazopanib at a dose of 800 mg orally daily for 4 week cycle. Results: Nineteen patients were enrolled. Median age was 66 years, with > 89% of patients presenting poorly differentiated bladder cancer. Adverse event data is available on 18 patients. No grade 4 or 5 events have been experienced. Nine patients have experienced 11 grade 3 adverse events of which 7 were deemed at least possibly related to treatment. Most common toxicities were anemia, thrombocytopenia, leucopenia and fatigue. For stage 1, none of the first 16 evaluable patients were deemed success (CR or PR) by the RECIST criteria during the first four 4-week cycles of treatment. Median progression- free survival was 1.9 months. This met the futility stopping rule of interim analysis, and therefore, the trial was recommended to be permanently closed. Correlative studies including measurement of VEGF levels in archived tissues and blood are pending. Conclusions: Pazopanib did not show activity in urothelial carcinoma patients. The role of anti-VEGF therapies in urothelial carcinoma may need further evaluation in rational combination strategies. [Table: see text]