1 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet2 unknown3 Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet4 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet5 Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
: 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 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 µg/mL increase in concentration. These results exclude a clinically important effect of aflibercept on ventricular repolarization.
Journal of Cardiovascular Pharmacology, 2013, Vol 61, Issue 6, p. 495-504