INTRODUCTION: Vandetanib is a once-daily oral agent that selectively inhibits vascular endothelial growth factor receptor, epidermal growth factor receptor, and RET (REarranged during Transfection) signaling. METHODS: This Phase I study investigated the safety, tolerability, and pharmacokinetics of vandetanib when administered with either gemcitabine plus cisplatin (GC) or vinorelbine plus cisplatin (VC) in patients with previously untreated locally advanced or metastatic non-small cell lung cancer. RESULTS: Seventeen patients received vandetanib 100 mg/d plus VC (n = 9) or GC (n = 8). Three dose-limiting toxicities were reported in each treatment group: vandetanib + VC (pulmonary artery thrombosis and asymptomatic QTc prolongation [n = 2]); vandetanib + GC (peripheral ischemia [due to arterial occlusion], pulmonary embolism, and limb venous thrombosis). The protocol definition of a tolerable dose was not met, and no patients were recruited to receive vandetanib 300 mg plus VC or GC. There was no apparent pharmacokinetic interaction between vandetanib and vinorelbine or gemcitabine, but there was an approximate 30% increase in the exposure to cisplatin, which may be due to accumulation of total platinum and/or an interaction with vandetanib. CONCLUSIONS: In this study, in patients with previously untreated advanced non-small cell lung cancer, vandetanib 100 mg/d in combination with either VC or GC was not tolerated.
INTRODUCTION: Vandetanib is a once-daily oral agent that selectively inhibits vascular endothelial growth factor receptor, epidermal growth factor receptor, and RET (REarranged during Transfection) signaling. METHODS: This Phase I study investigated the safety, tolerability, and pharmacokinetics of vandetanib when administered with either gemcitabine plus cisplatin (GC) or vinorelbine plus cisplatin (VC) in patients with previously untreated locally advanced or metastatic non-small cell lung cancer. RESULTS: Seventeen patients received vandetanib 100 mg/d plus VC (n = 9) or GC (n = 8). Three dose-limiting toxicities were reported in each treatment group: vandetanib + VC (pulmonary artery thrombosis and asymptomatic QTc prolongation [n = 2]); vandetanib + GC (peripheral ischemia [due to arterial occlusion], pulmonary embolism, and limb venous thrombosis). The protocol definition of a tolerable dose was not met, and no patients were recruited to receive vandetanib 300 mg plus VC or GC. There was no apparent pharmacokinetic interaction between vandetanib and vinorelbine or gemcitabine, but there was an approximate 30% increase in the exposure to cisplatin, which may be due to accumulation of total platinum and/or an interaction with vandetanib. CONCLUSIONS: In this study, in patients with previously untreated advanced non-small cell lung cancer, vandetanib 100 mg/d in combination with either VC or GC was not tolerated.
Authors: Michael Z Liao; Shannon K Flood Nichols; Mahmoud Ahmed; Shannon Clark; Gary D Hankins; Steve Caritis; Raman Venkataramanan; David Haas; Sara K Quinney; Laura S Haneline; Alan T Tita; Tracy Manuck; Joanne Wang; Kenneth E Thummel; Linda Morris Brown; Zhaoxia Ren; Thomas R Easterling; Mary F Hebert Journal: Drug Metab Dispos Date: 2020-01-24 Impact factor: 3.922
Authors: Zhen Ye Xu; Chang Juan Jin; Cai Cun Zhou; Zhong Qi Wang; Wei Dong Zhou; Hai Bin Deng; Ming Zhang; Wan Su; Xiao Yue Cai Journal: J Cancer Res Clin Oncol Date: 2011-02-05 Impact factor: 4.553
Authors: Elizabeth R Kessler; S Gail Eckhardt; Todd M Pitts; Erica L Bradshaw-Pierce; Cindy L O'byrant; Wells A Messersmith; Sujatha Nallapreddy; Colin Weekes; Jennifer Spratlin; Christopher H Lieu; Madeleine A Kane; Sarah Eppers; Elizabeth Freas; Stephen Leong Journal: Invest New Drugs Date: 2015-12-30 Impact factor: 3.850
Authors: Philipp Harter; Jalid Sehouli; Rainer Kimmig; Jörn Rau; Felix Hilpert; Christian Kurzeder; Gabriele Elser; Andreas du Bois Journal: Invest New Drugs Date: 2013-09-05 Impact factor: 3.850