Article

Combined treatment with pazopanib and vinflunine in patients with advanced urothelial carcinoma refractory after first-line therapy.

aDepartment of Urology, Lukas Hospital bGerman Centre for Assessment and Evaluation of Innovative Techniques in Medicine (DZITM), Neuss cDepartment of Urology, HELIOS Hospital, Bad Saarow, Germany.
Anti-cancer drugs (Impact Factor: 1.89). 04/2013; 24(4):422-5. DOI: 10.1097/CAD.0b013e32835efe78
Source: PubMed

ABSTRACT The role of pazopanib in the second-line setting of refractory metastatic transitional cell carcinoma of the urothelium has not been defined clearly. The aim of this phase I/II trial was to assess the safety, tolerability, and efficacy of combining pazopanib and vinflunine in patients with metastatic transitional cell carcinoma of the urothelium after failure of first-line platinum-containing therapy. From May 2011 to December 2011, five patients were enrolled in this trial. Pazopanib was the investigated compound; four levels were planned (200, 400, 600, and 800 mg/day). Vinflunine was dosed at 280 mg/m for the first dose and 320 mg/m every 3 weeks thereafter. After the definition of a tolerated dose for the combined therapy, a subsequent phase II study was planned. At the starting level, pazopanib 200 mg/day, dose-limiting toxicities were observed in two of five patients. One patient experienced grade 4 febrile neutropenia, which led to treatment discontinuation. A second patient showed grade 3 hepatobiliary disorder with an increase in γ-glutamyltransferase. The study was interrupted at dose level 1 for safety reasons. The initially planned phase II study was therefore not carried out. This phase I study showed that combined therapy of daily pazopanib (200 mg) and vinflunine (280/320 mg/m) every 3 weeks is poorly tolerated in patients with refractory advanced urothelial cancer.

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