| dc.description.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. | en_US |
| dc.description.sponsorship | Supported by Sanofi-Aventis to the QUTIE study P. Maison-Blanche has previously received money from Sanofi-Aventis for consulting fees and participation in review activities for the present work and consulting fees outside the present work; T. Goksel has previously received consulting fees/honorarium for himself and for his institution from Sanofi; J.-P. Machiels receives ongoing research grants for his institution from Sanofi for research in head and neck cancer; S. Rottey has previously received money for her institution from Sanofi for support for travel to meetings and provision of writing assistance/medicines/ equipment/administrative support for the present work, as well as money for her institution from Sanofi for consultancy, grants, and travel expenses outside the present work and money for herself as payment for lectures; G. Daugaard has received grant money for her institute from Sanofi for inclusion of patients and has personally received money from Sanofi for consultancy and for lectures; C. Volovat received grant money for himself and for his institution from Sanofi-Aventis; L. Sengelov has previously received support for travel for her institution from Sanofi-Aventis and provision of writing assistance/medicines/equipment/administrative support for the present work and money for her institution from Sanofi-Aventis as consultancy fees and payment for lectures outside the present work; A. Eniu has previously received grant money for himself and for his institution from Sanofi-Aventis; E. Jager has received money for her institution from Sanofi for case-by-case therapy-related payments; E. Meiri has received money for his institution from Sanofi to fund travel to meetings; S. Cascinu receives ongoing money from Sanofi for board membership; M. Clemens has received support for travel to meetings and payment for lectures from Sanofi-Aventis; E. Boelle is currently employed by Sanofi and has stock in Sanofi; E. Magherini is currently employed by Sanofi and has stock in Sanofi. For the remaining authors (J. B. Vermorken, S. Agarwala, M. Scheulen, D. Grecea, D. Strumberg, G. Demir, G. Pinotti, M. Nardi, and T. Guthrie), none were declared. None of the authors of the present manuscript receive funding from any of the following bodies: National Institutes of Health, Wellcome Trust, or Howard Hughes Medical Institute. | en_US |
| dc.department-temp | [Maison-Blanche, Pierre] Hop Bichat Claude Bernard, Dept Cardiol, F-75018 Paris, France -- [Vermorken, Jan B.] Antwerpen Univ Hosp, Dept Med Oncol, Edegem, Belgium -- [Goksel, Tuncay] Ege Univ, Tip Fak, Gogus Hast AD, Dept Pulm Med Izmir, Izmir, Turkey -- [Machiels, Jean-Pascal] Catholic Univ Louvain, Clin Univ St Luc, Dept Med Oncol, B-1200 Brussels, Belgium -- [Agarwala, Sanjiv] St Lukes Hosp, Bethlehem, PA USA -- [Rottey, Sylvie] Ghent Univ Hosp, Dept Med Oncol, Ghent, Belgium -- [Daugaard, Gedske] Rigshosp, Dept Oncol, DK-2100 Copenhagen, Denmark -- [Volovat, Constantin] Ctr Med Oncol Iasi, Iasi, Romania -- [Scheulen, Max] Univ Klinikum Essen, West German Canc Ctr, Innere Klin Tumorforsch, Essen, Germany -- [Sengelov, Lisa] Herlev Hosp, Dept Oncol, Dept Breast Tumors, DK-2730 Herlev, Denmark -- [Grecea, Dana -- Eniu, Alexandru] Inst Oncol Prof Dr Chiricuta, Cluj Napoca, Romania -- [Jaeger, Elke] Krankenhaus NW Frankfurt, Med Klin 2, Dept Hematol Oncol, Frankfurt, Germany -- [Meiri, Eyal] Palm Beach Inst Hematol & Oncol, Boynton Beach, FL USA -- [Cascinu, Stefano] Azienda Osped Univ Osped Riuniti, Clin Oncol Med, Ancona, Italy -- [Strumberg, Dirk] Marienhosp Herne, Dept Hematol & Med Oncol, Herne, Germany -- [Demir, Gokhan] Istanbul Bilim Univ, Tip Fak, Dept Med Oncol, Istanbul, Turkey -- [Clemens, Michael] Klinikum Mutterhaus Borromaerinnen, Innere Med Klin 1, Trier, Germany -- [Pinotti, Graziella] Osped Circolo E Fdn Macchi, Varese, Italy -- [Nardi, Mario] Azienda Osped Bianchi Melacrino Morelli, Div Oncol, Reggio Di Calabria, Italy -- [Guthrie, Troy] Baptist Reg Canc Inst, Jacksonville, FL USA -- [Boelle, Emmanuelle -- Magherini, Emmanuelle] Sanofi R&D, R&D Oncol Div, Vitry Sur Seine, France | en_US |
