title: Targeted Cancer Therapies and QT Interval Prolongation: Unveiling the Mechanisms Underlying Arrhythmic Complications and the Need for Risk Stratification Strategies.
abstract: 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.
authors.affiliation: Department of Cardiology, Azienda Ospedaliera Ordine Mauriziano, Largo Filippo Turati nr. 62, 10128, Turin, Italy. rezi.cuni@gmail.com.
authors.forename: Rezarta
authors.identifier: http://orcid.org/0000-0003-1131-7065
authors.initials: R
authors.lastname: Cuni
authors.affiliation: Department of Cardiology, Azienda Ospedaliera Ordine Mauriziano, Largo Filippo Turati nr. 62, 10128, Turin, Italy.
authors.forename: Iris
authors.initials: I
authors.lastname: Parrini
authors.affiliation: Azienda Sanitaria Locale Torino 2 and Torino 3, Out of Hospital Cardiology Service, Turin, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Asteggiano
authors.affiliation: Department of Cardiology, Azienda Ospedaliera Ordine Mauriziano, Largo Filippo Turati nr. 62, 10128, Turin, Italy.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Conte
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D016503:Drug Delivery Systems; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology; D018570:Risk Assessment
chemical_list: D000970:Antineoplastic Agents