OBJECTIVES: Vascular endothelial growth factor has been shown to be overexpressed in several studies of hepatocellular carcinoma (HCC). Cediranib is a potent inhibitor of vascular endothelial growth factor signaling. We assessed the efficacy and toxicity of cediranib in patients with HCC. METHODS: Twenty-eight patients with unresectable or metastatic HCC were enrolled in this study. Patients received 45 mg of cediranib orally, once daily, for 28-day cycles. The primary objective of this phase II study was to assess 6-month survival. Secondary objectives were to assess tumor response, time to progression, and toxicity. RESULTS: All 28 patients were evaluable for efficacy outcomes. Twelve patients (42.9%) survived 6 months, 15 (53.6%) died within 6 months, and 1 (3.6%) was lost to follow-up before 6 months. The median overall survival was 5.8 months (95% confidence interval, 3.4-7.3 mo). No patients experienced confirmed response. The median time to progression was 2.8 months (95% confidence interval, 2.3-4.4 mo). Twenty-six patients (93%) experienced a grade 3+ adverse event with the most common adverse event s being fatigue (46%), anorexia (25%), hypertension (21%), and elevated alanine aminotransferase (18%). CONCLUSIONS: Owing to the toxicity, cediranib at this dose and schedule is not an effective treatment in patients with unresectable or metastatic HCC.
OBJECTIVES:Vascular endothelial growth factor has been shown to be overexpressed in several studies of hepatocellular carcinoma (HCC). Cediranib is a potent inhibitor of vascular endothelial growth factor signaling. We assessed the efficacy and toxicity of cediranib in patients with HCC. METHODS: Twenty-eight patients with unresectable or metastatic HCC were enrolled in this study. Patients received 45 mg of cediranib orally, once daily, for 28-day cycles. The primary objective of this phase II study was to assess 6-month survival. Secondary objectives were to assess tumor response, time to progression, and toxicity. RESULTS: All 28 patients were evaluable for efficacy outcomes. Twelve patients (42.9%) survived 6 months, 15 (53.6%) died within 6 months, and 1 (3.6%) was lost to follow-up before 6 months. The median overall survival was 5.8 months (95% confidence interval, 3.4-7.3 mo). No patients experienced confirmed response. The median time to progression was 2.8 months (95% confidence interval, 2.3-4.4 mo). Twenty-six patients (93%) experienced a grade 3+ adverse event with the most common adverse event s being fatigue (46%), anorexia (25%), hypertension (21%), and elevated alanine aminotransferase (18%). CONCLUSIONS: Owing to the toxicity, cediranib at this dose and schedule is not an effective treatment in patients with unresectable or metastatic HCC.
Authors: Stephen R Wedge; Jane Kendrew; Laurent F Hennequin; Paula J Valentine; Simon T Barry; Sandra R Brave; Neil R Smith; Neil H James; Michael Dukes; Jon O Curwen; Rosemary Chester; Janet A Jackson; Sarah J Boffey; Lyndsey L Kilburn; Sharon Barnett; Graham H P Richmond; Peter F Wadsworth; Mike Walker; Alison L Bigley; Sian T Taylor; Lee Cooper; Sarah Beck; Juliane M Jürgensmeier; Donald J Ogilvie Journal: Cancer Res Date: 2005-05-15 Impact factor: 12.701
Authors: Charles J Ryan; Walter M Stadler; Bruce Roth; Douglass Hutcheon; Shauna Conry; Thomas Puchalski; Charles Morris; Eric J Small Journal: Invest New Drugs Date: 2007-04-26 Impact factor: 3.850
Authors: P Mathurin; O Rixe; N Carbonell; B Bernard; P Cluzel; M F Bellin; D Khayat; P Opolon; T Poynard Journal: Aliment Pharmacol Ther Date: 1998-02 Impact factor: 8.171
Authors: Josep M Llovet; Sergio Ricci; Vincenzo Mazzaferro; Philip Hilgard; Edward Gane; Jean-Frédéric Blanc; Andre Cosme de Oliveira; Armando Santoro; Jean-Luc Raoul; Alejandro Forner; Myron Schwartz; Camillo Porta; Stefan Zeuzem; Luigi Bolondi; Tim F Greten; Peter R Galle; Jean-François Seitz; Ivan Borbath; Dieter Häussinger; Tom Giannaris; Minghua Shan; Marius Moscovici; Dimitris Voliotis; Jordi Bruix Journal: N Engl J Med Date: 2008-07-24 Impact factor: 91.245
Authors: Christina A K Kim; Julie Price-Hiller; Quincy S Chu; Keith Tankel; Ron Hennig; Michael B Sawyer; Jennifer L Spratlin Journal: Invest New Drugs Date: 2014-05-23 Impact factor: 3.850