title: A randomized, double-blind, placebo-controlled study to assess QTc interval prolongation of standard dose aflibercept in cancer patients treated with docetaxel.
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 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.
authors: Hôpital Bichat-Claude Bernard, Cardiology Department, Paris, France. ipmb@wanadoo.fr
authors: Pierre
authors: P
authors: Maison-Blanche
authors: Jan B
authors: JB
authors: Vermorken
authors: Tuncay
authors: T
authors: Goksel
authors: Jean-Pascal
authors: JP
authors: Machiels
authors: Sanjiv
authors: S
authors: Agarwala
authors: Sylvie
authors: S
authors: Rottey
authors: Gedske
authors: G
authors: Daugaard
authors: Constantin
authors: C
authors: Volovat
authors: Max
authors: M
authors: Scheulen
authors: Lisa
authors: L
authors: Sengeløv
authors: Dana
authors: D
authors: Grecea
authors: Alexandru
authors: A
authors: Eniu
authors: Elke
authors: E
authors: Jäger
authors: Eyal
authors: E
authors: Meiri
authors: Stefano
authors: S
authors: Cascinu
authors: Dirk
authors: D
authors: Strumberg
authors: Gokhan
authors: G
authors: Demir
authors: Michael
authors: M
authors: Clemens
authors: Graziella
authors: G
authors: Pinotti
authors: Mario
authors: M
authors: Nardi
authors: Troy
authors: T
authors: Guthrie
authors: Emmanuelle
authors: E
authors: Boelle
authors: Emmanuelle
authors: E
authors: Magherini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077143:Docetaxel; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011446:Prospective Studies; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D043823:Taxoids / Q000008:administration & dosage; D016276:Ventricular Function / Q000187:drug effects*
chemical_list: D011993:Recombinant Fusion Proteins; D043823:Taxoids; C533178:aflibercept; D000077143:Docetaxel; D040262:Receptors, Vascular Endothelial Growth Factor