Targeted Cancer Therapies and QT Interval Prolongation: Unveiling the Mechanisms Underlying Arrhythmic Complications and the Need for Risk Stratification Strategies.

The care and treatment of cancer patients has significantly changed in the last decade with a remarkable shift towards novel targeted therapies. These promising new drugs may represent effective and potentially life-saving therapeutic options in cancer patients, but are also emerging in the cardiotoxicity scenario for their arrhythmogenic potential due to their QT-prolonging activity. In this article we review the mechanisms underlying drug-induced QT interval prolongation and the classes of anticancer-targeted therapies most frequently responsible for this adverse event, with a particular focus on tyrosine kinase-targeting molecules. Since up to 49 % of serious adverse drug reactions (ADRs) and 58 % of potentially fatal ADRs may not appear on initial drug safety labels, we also review and discuss data from the post-marketing VigiBase safety reporting system, the World Health Organization's global database of ADRs. Finally, we discuss arrhythmic risk stratification and prevention strategies in the complex multiple-risk setting of cancer patients, paying particular attention to drug-drug interactions with common antimicrobial, psychotropic and antiemetic supportive care, and we also provide an electrocardiographic QT monitoring algorithm for patients who are candidates for targeted cancer therapies.