INTRODUCTION: Cediranib, a potent vascular endothelial growth factor inhibitor, demonstrated broad pre-clinical anti-tumour activity. This study evaluated escalating cediranib doses with combination chemotherapy in advanced non-small cell lung cancer patients. METHODS: Patients received cisplatin 80 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1 and 8 of a 3-week cycle, and daily oral cediranib at either 30 mg or 45 mg. Pharmacokinetics of all drugs were analysed, and response was assessed by RECIST. RESULTS: Fifteen patients were enrolled. No dose-limiting toxicities were observed during cycle 1. Fatigue, nausea, diarrhoea, anorexia and granulocytopaenia were common; hypertension was manageable. No grade 3/4 bleeding occurred. At 45 mg/d, fatigue, diarrhoea and thrombocytopaenia were increased; and headache, hoarseness and grade 2 hand-foot syndrome were observed. Cediranib had no effect on cisplatin elimination, but clearance of gemcitabine is significantly reduced in the presence of cediranib (p>0.02). Central review confirmed responses in four of 15 enrolled patients (26.7%, 95% CI 7.8-55%) and four of 12 evaluable patients (33.3%, 95% CI 9.9-65%). CONCLUSION: Cediranib at 30 mg daily can be combined with standard doses of cisplatin/gemcitabine with encouraging anti-tumour activity, and is the recommended phase III dose. Toxicity is increased, but is predictable and manageable.
INTRODUCTION:Cediranib, a potent vascular endothelial growth factor inhibitor, demonstrated broad pre-clinical anti-tumour activity. This study evaluated escalating cediranib doses with combination chemotherapy in advanced non-small cell lung cancerpatients. METHODS:Patients received cisplatin 80 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1 and 8 of a 3-week cycle, and daily oral cediranib at either 30 mg or 45 mg. Pharmacokinetics of all drugs were analysed, and response was assessed by RECIST. RESULTS: Fifteen patients were enrolled. No dose-limiting toxicities were observed during cycle 1. Fatigue, nausea, diarrhoea, anorexia and granulocytopaenia were common; hypertension was manageable. No grade 3/4 bleeding occurred. At 45 mg/d, fatigue, diarrhoea and thrombocytopaenia were increased; and headache, hoarseness and grade 2 hand-foot syndrome were observed. Cediranib had no effect on cisplatin elimination, but clearance of gemcitabine is significantly reduced in the presence of cediranib (p>0.02). Central review confirmed responses in four of 15 enrolled patients (26.7%, 95% CI 7.8-55%) and four of 12 evaluable patients (33.3%, 95% CI 9.9-65%). CONCLUSION:Cediranib at 30 mg daily can be combined with standard doses of cisplatin/gemcitabine with encouraging anti-tumour activity, and is the recommended phase III dose. Toxicity is increased, but is predictable and manageable.
Authors: David M Hyams; Arlene Chan; Celia de Oliveira; Raymond Snyder; Jeferson Vinholes; M William Audeh; Victor M Alencar; Janine Lombard; Bijoyesh Mookerjee; John Xu; Kathryn Brown; Paula Klein Journal: Invest New Drugs Date: 2013-06-26 Impact factor: 3.850
Authors: Channing J Paller; Penelope A Bradbury; S Percy Ivy; Lesley Seymour; Patricia M LoRusso; Laurence Baker; Larry Rubinstein; Erich Huang; Deborah Collyar; Susan Groshen; Steven Reeves; Lee M Ellis; Daniel J Sargent; Gary L Rosner; Michael L LeBlanc; Mark J Ratain Journal: Clin Cancer Res Date: 2014-08-15 Impact factor: 12.531
Authors: Tanja Trarbach; Beate Schultheis; Thomas C Gauler; Vesile Schneider; Dirk Strumberg; Wilfried E E Eberhardt; Stephanie Le Scouiller; Marcelo Marotti; Kathryn H Brown; Joachim Drevs Journal: Invest New Drugs Date: 2011-10-12 Impact factor: 3.850
Authors: Abdo J Najy; Young Suk Jung; Joshua J Won; M Katie Conley-LaComb; Allen Saliganan; Chong Jai Kim; Elisabeth Heath; Michael L Cher; R Daniel Bonfil; Hyeong-Reh Choi Kim Journal: Prostate Date: 2011-12-27 Impact factor: 4.104