A two-part Phase II study of cediranib in patients with advanced solid tumours: the effect of food on single-dose pharmacokinetics and an evaluation of safety, efficacy and imaging pharmacodynamics

Mitchell, C.L. et al. (2011) A two-part Phase II study of cediranib in patients with advanced solid tumours: the effect of food on single-dose pharmacokinetics and an evaluation of safety, efficacy and imaging pharmacodynamics. Cancer Chemotherapy and Pharmacology, 68(3), pp. 631-641. (doi: 10.1007/s00280-010-1534-3)

Abstract

Background: Cediranib (RECENTIN™) is an oral, highly potent VEGF inhibitor. This study evaluated the effect of food on the pharmacokinetics of cediranib and compared the administration of continual cediranib via two dosing strategies using this as a platform to investigate pharmacodynamic imaging biomarkers.

Methods: Sixty patients were randomised to receive two single doses of cediranib in either fed/fasted or fasted/fed state (Part A). In continual dosage phase (Part B), patients were randomised to a fixed-dose or dose-escalation arm. Exploratory pharmacodynamic assessments were performed using DCE-MRI and CT enhancing fraction (EnF).

Results: In part A, plasma AUC and C max of cediranib were lower in the presence of food by a mean of 24 and 33%, respectively (94% CI: AUC, 12–34% and C max, 20–43%), indicating food reduces cediranib plasma exposure. In part B, cediranib 30 mg/day appeared to be the most sustainable for chronic dosing. Continuous cediranib therapy was associated with sustained antivascular effects up to 16 weeks, with significant reductions in DCE-MRI parameters and CT EnF.

Conclusions: It is recommended that cediranib be administered at least 1 h before or 2 h after food. Evidence of antitumour activity was observed, with significant sustained effects upon imaging vascular parameters.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kelly, Mr Ciaran
• Authors: Mitchell, C.L., O’Connor, J.P.B., Roberts, C., Watson, Y., Jackson, A., Cheung, S., Evans, J., Spicer, J., Harris, A., Kelly, C., Rudman, S., Middleton, M., Fielding, A., Tessier, J., Young, H., Parker, G.J.M., and Jayson, G.C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cancer Chemotherapy and Pharmacology
• ISSN: 0344-5704
• Published Online: 01 December 2010