Chapter 1 - Cardiac Complications of Cancer and Anti-Cancer Treatment
Multiple conditions may cause arrhythmias in cancer patients. Fibrosis due to old age or radiation therapy, or coronary or myocardial disease secondary to cancer therapy, can all affect the cardiac conduction system. Several chemotherapeutic agents have been associated with bradycardia and heart block, the most clinically significant being paclitaxel (incidence of asymptomatic bradycardia up to 30% in phase II studies) and thalidomide (incidence ranging from 0.12% up to 55%). In addition, some new target agents such as crizotinib have also been associated with profound asymptomatic sinus bradycardia (in 5% of patients).
Evaluation and Treatment
Generally, bradycardia presents with an asymptomatic heart rate <50 beats/min; nevertheless, some patients may have associated symptoms such as fatigue, syncope or dizziness. Diagnostic tests include an ECG, Holter monitoring and screening for underlying disorders, such as thyroid disease or electrolyte abnormalities.
Bradycardia associated with paclitaxel is generally without clinical significance, as many cases are asymptomatic. However, if patients develop bradycardia with progressive atrioventricular conduction disturbances and/or clinically significant haemodynamic effects, paclitaxel discontinuation is warranted, and some patients might require pacemaker implantation. Whenever haemodynamic instability is imminent or life-threatening, active intervention according to advanced cardiac life-support protocols is mandatory.
With crizotinib, bradycardia presents as a pharmacodynamic effect, with hearth rate progressively decreasing when serum concentrations of this agent increase. Thus, special attention should be given to drug–drug interactions, which might result in an increased concentration of crizotinib. In addition, concurrent heart rate-lowering agents such as beta-blockers or CCBs should be used with caution in these patients.