PURPOSE: Greater scrutiny is being placed on developing a full understanding of potential cardiotoxicity of therapeutic agents, especially on the potential to prolong the QTc interval which can lead to arrhythmias such as torsade de pointes and sudden death. This trial was designed to specifically evaluate the effect, if any, of cetuximab on the QTc interval in patients with advanced solid tumors. METHODS: Cetuximab was administered as an initial dose of 400 mg/m(2) on day 1 (week 1) followed by a maintenance dose of 250 mg/m(2) weekly thereafter. ECG monitoring was performed at screening, baseline (week 1 preceding dosing), and during week 1 to 5 of treatment. Cetuximab concentration-to-QTc relationship was evaluated based on cetuximab serum samples obtained at the time of each ECG measurement to allow for accurate correlation between any observed QT/QTc changes and cetuximab serum concentration. RESULTS: At the recommended dose (400 mg/m(2) on day 1 followed by 250 mg/m(2) weekly), cetuximab had no clinically meaningful effect on QTc interval, PR or QRS intervals, or heart rate and there was no apparent concentration-dependent effect of cetuximab on any of these electrocardiogram parameters. Safety observations in patients treated with cetuximab in this study were consistent with the agent's known safety profile. CONCLUSION: These results suggest that cetuximab can be safely administered as a single agent without risk of effect on QTc interval.
PURPOSE: Greater scrutiny is being placed on developing a full understanding of potential cardiotoxicity of therapeutic agents, especially on the potential to prolong the QTc interval which can lead to arrhythmias such as torsade de pointes and sudden death. This trial was designed to specifically evaluate the effect, if any, of cetuximab on the QTc interval in patients with advanced solid tumors. METHODS:Cetuximab was administered as an initial dose of 400 mg/m(2) on day 1 (week 1) followed by a maintenance dose of 250 mg/m(2) weekly thereafter. ECG monitoring was performed at screening, baseline (week 1 preceding dosing), and during week 1 to 5 of treatment. Cetuximab concentration-to-QTc relationship was evaluated based on cetuximab serum samples obtained at the time of each ECG measurement to allow for accurate correlation between any observed QT/QTc changes and cetuximab serum concentration. RESULTS: At the recommended dose (400 mg/m(2) on day 1 followed by 250 mg/m(2) weekly), cetuximab had no clinically meaningful effect on QTc interval, PR or QRS intervals, or heart rate and there was no apparent concentration-dependent effect of cetuximab on any of these electrocardiogram parameters. Safety observations in patients treated with cetuximab in this study were consistent with the agent's known safety profile. CONCLUSION: These results suggest that cetuximab can be safely administered as a single agent without risk of effect on QTc interval.
Authors: Willemieke S Tummers; Sarah E Miller; Nutte T Teraphongphom; Adam Gomez; Idan Steinberg; David M Huland; Steve Hong; Sri-Rajasekhar Kothapalli; Alifia Hasan; Robert Ertsey; Bert A Bonsing; Alexander L Vahrmeijer; Rutger-Jan Swijnenburg; Teri A Longacre; George A Fisher; Sanjiv S Gambhir; George A Poultsides; Eben L Rosenthal Journal: Ann Surg Oncol Date: 2018-04-17 Impact factor: 5.344
Authors: Robert S Ackerman; Aaron R Muncey; Nasrin N Aldawoodi; Rohini Kotha; Rosemarie E Garcia Getting Journal: Curr Oncol Rep Date: 2022-02-10 Impact factor: 5.945
Authors: Rebecca W Gao; Nutte Teraphongphom; Esther de Boer; Nynke S van den Berg; Vasu Divi; Michael J Kaplan; Nicholas J Oberhelman; Steven S Hong; Elissa Capes; A Dimitrios Colevas; Jason M Warram; Eben L Rosenthal Journal: Theranostics Date: 2018-03-28 Impact factor: 11.556