Gemcitabine and atrial fibrillation: a rare manifestation of chemotherapy toxicity

Abstract

Gemcitabine is a purine analog with known activity in many solid tumors, namely lung, breast, pancreatic, genitourinary and head/neck cancers. Cardiac toxicity is a rare event and only one report previously described atrial fibrillation (AF) as a consequence of gemcitabine infusion. We report two cases of women suffering from lung cancer who were treated with gemcitabine. Both patients were admitted to hospital for paroxysmal AF occurring 12-24 h after the infusion of the drug. In the first case a sinus rhythm was spontaneously repristinated when AF occurred for the first time, while the second episode required an anti-arrhythmic drug to interrupt the dysrhythmia. In the second case, the patient had to be treated with digitalis glycoside to control the ventricular response without attaining a sinus rhythm. We could not recognize any other precipitating factor beyond the infusion of gemcitabine as a cause for the arrhythmia. Both cases were treated with gemcitabine for lung cancer and we observed the appearance of AF less than 24 h after drug administration. We assume that 2',2'-difluorodeoxyuridine, an active metabolite of gemcitabine, could be responsible for the toxic effect. We conclude that AF is an unusual, but potentially dangerous, side-effect of gemcitabine infusion. The arrhythmia should be suspected whenever patients complain of dyspnea and palpitations beginning 12-24 h after treatment. In these cases, the treatment of AF consists of anti-arrhythmic drugs in order to repristinate a sinus rhythm or control the heart rate.

Cardiac and cardiovascular toxicity of nonanthracycline anticancer drugs

“…There have been reports of atrial flutter and fibrillation in patients treated with gemcitabine [114][115][116][117]. An active metabolite of gemcitabine, 2´,2´-difluorodeoxyuridine, could be responsible for this toxicity [117].…”

Gemcitabine induced cardiomyopathy: a case of multiple hit cardiotoxicity

“…Most of these report supraventricular tachycardias including atrial fibrillation 8, 9. Atrial fibrillation is typically seen 18–24 h of infusion.…”

Atrial Fibrillation Induced by Gemcitabine Treatment in a 65-Year-Old Man

“…The prevalence increases with age -up to 4% in people over the age of 60 and approximately 9% in people over the age of 80. AF is usually not an immediately life-threatening arrhythmia but produces substantial discomfort and morbidity and may increase mortality, particularly in patients with structural heart disease [9][10][11][12]. AF is often associated with cardiovascular diseases such as heart failure, valvular heart diseases and hypertension as well as thyroid dysfunction and pulmonary disease.…”

“…Major side effects of the treatment with gemcitabine are hepatic dysfunction, myelosuppression, renal impairment, problems during concurrent radiotherapy (gemcitabine is a strong radiosensitizer) and pulmonary toxicity [14]. Recently, Ferrari et al [10] have reported on 2 patients who developed AF under gemcitabine therapy. They suggested that gemcitabine, and specifically its deaminated metabolite dFdU, could have a direct effect on the myocardial cells and the conduction system, evoking overstimulation of the sinoatrial node.…”

“…Atrial fibrillation (AF) is an uncommon side effect published in very few case reports in the literature [6][7][8][9][10]. In this report, we present the case of a patient who developed AF under gemcitabine therapy for stage IIIB nonsmall cell lung cancer.…”