QT Prolongation and Arrhythmias in Cancer Therapy: A Narrative Review of Mechanistic and Clinical Studies
Document Type
Article
Publication Title
Cardiovascular Toxicology
Abstract
Drug-induced QTc prolongation has emerged as a major, preventable cause of malignant ventricular arrhythmias in cancer therapy. This narrative review integrates mechanistic, clinical, and practical insights into QTc prolongation associated with antineoplastic and supportive medications. We outline direct ionic mechanisms, most notably hERG/IKr blockade and PI3K/Akt pathway modulation, as well as indirect contributors, including cytokine-mediated myocarditis, electrolyte disturbances, and structural remodeling. High-risk agents, including arsenic trioxide, vandetanib, nilotinib, sunitinib, and ribociclib, are contrasted with lower-risk alternatives and QT-sparing strategies. Polypharmacy and drug-drug interactions are emphasized as major real-world amplifiers of risk. Among supportive medications, fluoroquinolones, azole antifungals, and certain antiemetics frequently interact with QT-active anticancer agents, whereas beta-lactams, echinocandins, isavuconazole, and palonosetron may represent safer alternatives. We propose a mechanism-to-bedside framework that incorporates baseline ECG and electrolyte assessment, QT-risk stratification, and clear intervention thresholds (QTc ≥ 500 ms or an increase of ≥ 60 ms). Acute management of torsades de pointes, including intravenous magnesium and overdrive pacing, as well as structured hold-and-rechallenge algorithms, is also summarized. Finally, we highlight system-level measures, such as drug interaction stewardship, standardized discharge communication, and clinician education, to shift cardio-oncology practice from reactive arrhythmia management toward anticipatory prevention. This integrative synthesis aims to preserve oncologic efficacy while mitigating arrhythmic risk in modern cancer care.
DOI
10.1007/s12012-026-10130-x
Publication Date
5-23-2026
Keywords
Cardio-oncology, Drug–drug interactions, Polypharmacy, QT prolongation, Torsades de pointes, Tyrosine kinase inhibitors, hERG/IKr
ISSN
1559-0259
Recommended Citation
Ogunniyi KE, Djunadi TA, Ayedun SA, Onyenokwe V, Okuma OA, Sanji E, Greek A. QT Prolongation and Arrhythmias in Cancer Therapy: A Narrative Review of Mechanistic and Clinical Studies. Cardiovascular Toxicology. 2026; 26(6). doi: 10.1007/s12012-026-10130-x.
