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Title
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A randomized, double-blind, placebo-controlled study to assess QTc interval prolongation of standard dose aflibercept in cancer patients treated with docetaxel
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Author
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Abstract
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| 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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Language
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English
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Source (journal)
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Journal of cardiovascular pharmacology. - New York
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Publication
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New York
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2013
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ISSN
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0160-2446
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DOI
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10.1097/FJC.0B013E31828B73FF
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Volume/pages
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61
:6
(2013)
, p. 495-504
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ISI
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000330350300008
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Full text (Publisher's DOI)
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