PURPOSE: Vandetanib is an oral once-daily tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 and epidermal growth factor receptor. Vandetanib in combination with docetaxel was assessed in patients with advanced urothelial cancer (UC) who progressed on prior platinum-based chemotherapy. PATIENTS AND METHODS: The primary objective was to determine whether vandetanib 100 mg plus docetaxel 75 mg/m(2) intravenously every 21 days prolonged progression-free survival (PFS) versus placebo plus docetaxel. The study was designed to detect a 60% improvement in median PFS with 80% power and one-sided α at 5%. Patients receiving docetaxel plus placebo had the option to cross over to single-agent vandetanib at progression. Overall survival (OS), overall response rate (ORR), and safety were secondary objectives. RESULTS: In all, 142 patients were randomly assigned and received at least one dose of therapy. Median PFS was 2.56 months for the docetaxel plus vandetanib arm versus 1.58 months for the docetaxel plus placebo arm, and the hazard ratio for PFS was 1.02 (95% CI, 0.69 to 1.49; P = .9). ORR and OS were not different between both arms. Grade 3 or higher toxicities were more commonly seen in the docetaxel plus vandetanib arm and included rash/photosensitivity (11% v 0%) and diarrhea (7% v 0%). Among 37 patients who crossed over to single-agent vandetanib, ORR was 3% and OS was 5.2 months. CONCLUSION: In this platinum-pretreated population of advanced UC, the addition of vandetanib to docetaxel did not result in a significant improvement in PFS, ORR, or OS. The toxicity of vandetanib plus docetaxel was greater than that for vendetanib plus placebo. Single-agent vandetanib activity was minimal.
PURPOSE: Vandetanib is an oral once-daily tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 and epidermal growth factor receptor. Vandetanib in combination with docetaxel was assessed in patients with advanced urothelial cancer (UC) who progressed on prior platinum-based chemotherapy. PATIENTS AND METHODS: The primary objective was to determine whether vandetanib 100 mg plus docetaxel 75 mg/m(2) intravenously every 21 days prolonged progression-free survival (PFS) versus placebo plus docetaxel. The study was designed to detect a 60% improvement in median PFS with 80% power and one-sided α at 5%. Patients receiving docetaxel plus placebo had the option to cross over to single-agent vandetanib at progression. Overall survival (OS), overall response rate (ORR), and safety were secondary objectives. RESULTS: In all, 142 patients were randomly assigned and received at least one dose of therapy. Median PFS was 2.56 months for the docetaxel plus vandetanib arm versus 1.58 months for the docetaxel plus placebo arm, and the hazard ratio for PFS was 1.02 (95% CI, 0.69 to 1.49; P = .9). ORR and OS were not different between both arms. Grade 3 or higher toxicities were more commonly seen in the docetaxel plus vandetanib arm and included rash/photosensitivity (11% v 0%) and diarrhea (7% v 0%). Among 37 patients who crossed over to single-agent vandetanib, ORR was 3% and OS was 5.2 months. CONCLUSION: In this platinum-pretreated population of advanced UC, the addition of vandetanib to docetaxel did not result in a significant improvement in PFS, ORR, or OS. The toxicity of vandetanib plus docetaxel was greater than that for vendetanib plus placebo. Single-agent vandetanib activity was minimal.
Authors: D F Bajorin; P M Dodd; M Mazumdar; M Fazzari; J A McCaffrey; H I Scher; H Herr; G Higgins; M G Boyle Journal: J Clin Oncol Date: 1999-10 Impact factor: 44.544
Authors: David J Gallagher; Matthew I Milowsky; Scott R Gerst; Nicole Ishill; Jamie Riches; Ashley Regazzi; Mary G Boyle; Alisa Trout; Anne-Marie Flaherty; Dean F Bajorin Journal: J Clin Oncol Date: 2010-02-08 Impact factor: 44.544
Authors: Marissa Shrader; Maria Simona Pino; Gordon Brown; Peter Black; Liana Adam; Menahse Bar-Eli; Colin P N Dinney; David J McConkey Journal: Mol Cancer Ther Date: 2007-01 Impact factor: 6.261
Authors: Christopher J Sweeney; Bruce J Roth; Fairooz F Kabbinavar; David J Vaughn; Michael Arning; Rafael E Curiel; Coleman K Obasaju; Yanping Wang; Steven J Nicol; Donald S Kaufman Journal: J Clin Oncol Date: 2006-07-20 Impact factor: 44.544
Authors: Christian Wülfing; Jean-Pascal H Machiels; Dirk J Richel; Marc-Oliver Grimm; Uwe Treiber; Marco R De Groot; Philippe Beuzeboc; Roma Parikh; Frank Pétavy; Iman A El-Hariry Journal: Cancer Date: 2009-07-01 Impact factor: 6.860
Authors: Roy S Herbst; Yan Sun; Wilfried E E Eberhardt; Paul Germonpré; Nagahiro Saijo; Caicun Zhou; Jie Wang; Longyun Li; Fairooz Kabbinavar; Yukito Ichinose; Shukui Qin; Li Zhang; Bonne Biesma; John V Heymach; Peter Langmuir; Sarah J Kennedy; Hiroomi Tada; Bruce E Johnson Journal: Lancet Oncol Date: 2010-07 Impact factor: 41.316
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