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document
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 . 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 .
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Intervention_Pharmacological
cediranib
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Outcome_Other
safety
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Outcome_Other
efficacy
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Outcome_Other
imaging pharmacodynamics
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Outcome_Physical
plasma AUC and C ( max ) of cediranib
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Outcome_Physical
sustained antivascular effects
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Outcome_Physical
DCE-MRI parameters and CT
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Participant_Condition
advanced solid tumours
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Participant_Sample-size
Sixty patients