Clinical QTc Assessment in Oncology

  • Margaret R. BrittoEmail author
  • Nenad Sarapa


Cardiac proarrhythmia due to drug-induced QTc interval prolongation is an important concern in oncology since novel therapies can result in prolonged survival of cancer patients already predisposed to cardiotoxicity, and a number of anticancer agents, such as some of the tyrosine kinase inhibitors, are known to cause this risk. While not specifically requested by the ICH E14 guidance, a certain degree of QTc assessment in preapproval trials has emerged as the regulatory expectation with novel anticancer agents, particularly those that are small molecule chemical entities. This chapter reviews the challenges of evaluating QTc effect in oncology and proposes three integrated approaches to QTc risk assessment of anticancer agents (i.e., a “classic ICH E14-type” scenario, a “front-loaded” scenario, and a “full-development” scenario), which can be customized to different development plans and be evaluated using quantitative outcome criteria.


ECG Electrocardiogram Thorough QT Concentration-QT TQT Clinical trials Cardiac repolarization 


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Pharmacokinetics/PharmacodynamicsQuintiles, Inc.Overland ParkUSA
  2. 2.Clinical Sciences OncologyBayer Healthcare, Inc.WhippanyUSA

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