title: QTc prolongation induced by targeted biotherapies used in clinical practice and under investigation: a comprehensive review.
abstract: In anticancer drug development, there has been increasing consideration for the potential of a compound to cause adverse electrocardiographic changes, especially QT interval prolongation, which can be associated with risk of torsades de pointes and sudden death. Irrespective of overt clinical toxicities, QTc assessment can influence decision making during the conduct of clinical studies, including eligibility for protocol therapy, dose delivery or discontinuation, and analyses of optimal dose for subsequent development. Efforts are needed to refine strategies for risk management, avoiding unintended consequences that negatively affect patient access and clinical development of promising new cancer treatments. In this comprehensive review, we will analyze potential effects on QTc prolongations of targeted agents approved by regulatory agencies and under investigation. A thoughtful risk management plan was generated by an organized collaboration between oncologists, cardiologists, and regulatory agencies to support a development program essential for oncology agents with cardiac safety concerns.
authors: Early Drug Development for Innovative Therapy Division, European Institute of Oncology, Milan, Italy.
authors: Marzia
authors: M
authors: Locatelli
authors: Carmen
authors: C
authors: Criscitiello
authors: Angela
authors: A
authors: Esposito
authors: Ida
authors: I
authors: Minchella
authors: Aron
authors: A
authors: Goldhirsch
authors: Carlo
authors: C
authors: Cipolla
authors: Giuseppe
authors: G
authors: Curigliano
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D053840:Brugada Syndrome; D000075224:Cardiac Conduction System Disease; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000002:abnormalities*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000009:adverse effects*; D012308:Risk Management
chemical_list: D000970:Antineoplastic Agents