Antineoplastic Chemotherapy Induced QTc Prolongation

Abstract

Anticancer drugs are sometimes associated with QT prolongation. Classical, new and candidate agents to treat cancer may affect ventricular repolarization through a set of different mechanisms. Interference on human ether-a-go-go-related gene potassium ion channels (HERG K+) seems to be a common mechanism for many of these drugs. Anthracycline chemotherapy is associated with electrocardiographic alterations including prolongation of QT interval, development of ventricular late potentials and various arrhythmias. The effects of the interaction of anthracyclines with the monoclonal antibody against HER2/neu (Erb-2) trastuzumab could potentiate the cardiotoxic effects. Electrocardiographic changes have been also reported with the use of 5-fluorouracil. QTc alterations have also been reported with some platinum compounds. Taxanes (paclitaxel and docetaxel) have also been associated with cardiotoxicity, promoting both bradi- and tachyarrhythmias and other cardiac disturbances. Among the newest compounds, symptomatic or asymptomatic QTc aberrations were reported with multitargeted tyrosine-kinase inhibitors, anti HERG2, anti-VEGF, vascular disruption agents and histone deacetylase inhibitors. Patients with cancer are at increased risk of sudden death due to severe cardiac arrhythmias because of the high prevalence of predisposing risk factors such as electrolytic abnormalities, starvation and concomitant medications. The use of specific anticancer drug that may prolong the QT interval need to be properly evaluated in each case to reduce this risk.

Long-term Cardiovascular Toxicity in Children, Adolescents, and Young Adults Who Receive Cancer Therapy: Pathophysiology, Course, Monitoring, Management, Prevention, and Research Directions

“…Anthracyclines, such as doxorubicin, daunorubicin, epirubicin, and idarubicin, have been associated with prolonged corrected QT (QTc) intervals as measured by surface electrocardiography, a finding that indicates a risk of ventricular tachycardia. 55,56 They have also been directly associated with premature ventricular contractions, sinus node dysfunction, ventricular late potentials, and decreased QRS voltage. The incidence of these findings ranges from 10% to 30%.…”

Epigenetics of thyroid cancer and novel therapeutic targets

“…On the whole, the HDACi are well tolerated and produce minimal adverse effects. However, cardiac arrhythmias seem to be relatively frequent, and hence these agents should probably be used with caution in patients with heart disease (Prince et al 2009, Bagnes et al 2010.…”

Ventricular Repolarization Intervals in Children Previously Treated with Anthracyclines

“…A possible drawback in that study was the lack of more accurate digital measurements. More recent studies have reinforced the association between anthracycline and prolonged corrected QT (QTc) intervals as measured on surface the surface electrocardiogram, which may point to heightened risk of ventricular tachycardia [12,13] Anthracyclines have been directly associated with premature ventricular contractions, sinus node dysfunction, ventricular late potentials, and decreased QRS voltage. The incidence of such occurrence ranges from 10% to 30% [14,15].…”