Title
A randomized, double-blind, placebo-controlled study to assess QTc interval prolongation of standard dose aflibercept in cancer patients treated with docetaxel A randomized, double-blind, placebo-controlled study to assess QTc interval prolongation of standard dose aflibercept in cancer patients treated with docetaxel
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
New York ,
Subject
Pharmacology. Therapy
Human medicine
Source (journal)
Journal of cardiovascular pharmacology. - New York
Volume/pages
61(2013) :6 , p. 495-504
ISSN
0160-2446
ISI
000330350300008
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
The effect of repeated doses of aflibercept on ventricular repolarization in cancer patients was evaluated in an intensive electrocardiogram trial. This randomized, placebo-controlled, double-blind trial was conducted in 87 treated solid tumor patients. Treatment was with 6 mg/kg aflibercept, 1-hour intravenous (n = 43), or placebo (n = 44), combined with <= 75 mg/m(2) docetaxel, every 3 weeks. Electrocardiograms were collected for 6 hours posttreatment using digital 12-lead Holter recorders, at day 1, in cycles 1 and 3. Free and vascular endothelial growth factor-bound aflibercept concentrations were assessed at similar time points. Eighty-four patients (43 placebo and 41 aflibercept) were evaluable for QT interval, Fridericia correction (QTcF) at cycle 1 and 59 (31 placebo and 28 aflibercept) at cycle 3. During cycle 3, from 30 minutes to 6 hours after the start of aflibercept, the maximum observed upper limit of the QTcF 90% confidence interval was 16 ms, for a mean of 8.4 ms. QTcF prolongation above 480 ms and 60 ms above baseline was observed in 1 aflibercept patient (2%). The slope of the relationship between free aflibercept concentration and QTcF was 0.048 (95% confidence interval, 0.013-0.082), corresponding to a 5-ms increase per 100 mg/mL increase in concentration. These results exclude a clinically important effect of aflibercept on ventricular repolarization.
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