ABSTRACT: The effect of repeated doses of aflibercept on ventricular repolarization in cancer patients was evaluated in an intensive ECG trial. This randomized, placebo-controlled, double blind trial was conducted in 87 treated solid tumor patients. Treatment was with aflibercept 6 mg/kg, 1-hr IV (n=43) or placebo (n=44), combined with docetaxel ≤75 mg/m, q3 weeks. ECGs were collected for 6 hours post-treatment using digital 12-lead Holter recorders, at day 1, in Cycles 1 and 3. Free and VEGF-bound aflibercept concentrations were assessed at similar time points. Eighty-four patients (43 placebo, 41 aflibercept) were evaluable for QTcF at Cycle 1 and 59 (31 placebo, 28 aflibercept) at Cycle 3. During Cycle 3, from 30 min to 6 hours after the start of aflibercept, the maximum observed upper limit of the QTcF 90\%CI was 16 ms, for a mean of 8.4 ms. QTcF prolongation above 480 ms and 60 ms above baseline was observed in one aflibercept patient (2\%). The slope of the relationship between free aflibercept concentration and QTcF was 0.048 (95\%CI, 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.
|Data di pubblicazione:||2013|
|Titolo:||A randomized, double blind, placebo-controlled study to assess QTc interval prolongation of standard dose aflibercept in cancer patients treated with docetaxel.|
|Autori:||P. Maison-Blanche; J. B. Vermorken; T. Goksel; J. Machiels; S. Agarwala; S. Rottey; G. Daugaard; C. Volovat; M. Scheulen; L. Sengeløv; D. Grecea; A. Eniu; E. Jäger; E. Meiri; S. Cascinu; D. Strumberg; G. Demir; M. Clemens; G. Pinotti; M. Nardi; T. Guthrie; E. Boelle; E. Magherini|
|Digital Object Identifier (DOI):||10.1097/FJC.0b013e31828b73ff|
|Appare nelle tipologie:||Articolo su rivista|
File in questo prodotto:
I documenti presenti in Iris Unimore sono rilasciati con licenza Creative Commons Attribuzione - Non commerciale - Non opere derivate 3.0 Italia, salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris