What are the cardiac side effects of Paclitaxel (Taxol)?

From the Guidelines

Taxol (paclitaxel) can cause cardiac side effects, including myocardial ischemia and infarction, which occur in approximately 3% of patients receiving the drug, with a higher incidence in those with known cardiac risk factors such as hypertension and coronary artery disease. The cardiac side effects of Taxol are a significant concern, and healthcare providers should be aware of the potential risks, especially in patients with pre-existing cardiac disease. According to a study published in the Journal of the American College of Cardiology 1, the overall incidence of grade 4 and 5 cardiac events was only 0.29% in patients treated with paclitaxel. Some key points to consider when administering Taxol include:

• Cardiac monitoring is recommended during the first course of treatment, particularly for high-risk patients
• Premedication with antihistamines, corticosteroids, and H2 blockers can help reduce cardiac side effects
• Slower infusion rates may also decrease cardiac side effects
• Healthcare providers should perform baseline cardiac evaluation before starting Taxol therapy and monitor patients closely during treatment, especially those with cardiovascular risk factors or pre-existing heart conditions It's also important to note that the combination of Taxol with other chemotherapy agents, such as anthracyclines, can increase the risk of cardiac side effects, and therefore, it's recommended to administer anthracyclines before paclitaxel, separate the infusions, and/or limit the cumulative doxorubicin dose to 360 mg/m2, as suggested by the European Society of Cardiology 1.

From the FDA Drug Label

Cardiovascular: Hypotension, during the first 3 hours of infusion, occurred in 12% of all patients and 3% of all courses administered. Bradycardia, during the first 3 hours of infusion, occurred in 3% of all patients and 1% of all courses. In the Phase 3 second-line ovarian study, neither dose nor schedule had an effect on the frequency of hypotension and bradycardia These vital sign changes most often caused no symptoms and required neither specific therapy nor treatment discontinuation. The frequency of hypotension and bradycardia were not influenced by prior anthracycline therapy. Significant cardiovascular events possibly related to single-agent paclitaxel occurred in approximately 1% of all patients These events included syncope, rhythm abnormalities, hypertension and venous thrombosis. One of the patients with syncope treated with paclitaxel at 175 mg/m2 over 24 hours had progressive hypotension and died. The arrhythmias included asymptomatic ventricular tachycardia, bigeminy and complete AV block requiring pacemaker placement Among patients with NSCLC treated with paclitaxel in combination with cisplatin in the Phase 3 study, significant cardiovascular events occurred in 12 to 13%. This apparent increase in cardiovascular events is possibly due to an increase in cardiovascular risk factors in patients with lung cancer.

Cases of myocardial infarction have been reported Congestive heart failure, including cardiac dysfunction and reduction of left ventricular ejection fraction or ventricular failure, has been reported typically in patients who have received other chemotherapy, notably anthracyclines. (See PRECAUTIONS: Drug Interactions section.) Atrial fibrillation and supraventricular tachycardia have been reported.

Cardiac side effects of Taxol (paclitaxel) include:

• Hypotension
• Bradycardia
• Syncope
• Rhythm abnormalities
• Hypertension
• Venous thrombosis
• Myocardial infarction
• Congestive heart failure
• Atrial fibrillation
• Supraventricular tachycardia These events occurred in approximately 1% of patients treated with single-agent paclitaxel, and more frequently in patients treated with paclitaxel in combination with cisplatin 2.

From the Research

Cardiac Side Effects of Taxol

• Taxol, also known as paclitaxel, is an anticancer agent used to treat various types of cancer, including breast and ovarian cancer 3.
• The major side effects of Taxol include bone marrow suppression, alopecia, polyneuropathy, and cardiac toxicity, such as bradycardia, myocardial infarction, congestive heart failure, and cardiac death 3.
• Cardiac toxicity associated with Taxol can manifest as asymptomatic sinus bradycardia, heart block, conduction abnormalities, atrial and ventricular arrhythmias, and cardiac ischemia 4.
• The incidence of serious cardiac events is low, but patients with cardiac risk factors, such as pre-existing cardiac disease or those taking medications that alter cardiac conduction, should be closely monitored 4.

Specific Cardiac Side Effects

• Atrial fibrillation is a rare but severe reaction to Taxol cardiotoxicity, with an incidence of 1.0-1.7% worldwide 5.
• Bradycardia and conduction abnormalities, such as third-degree heart block, can occur in patients treated with Taxol 3, 6.
• Cardiac ischemia and myocardial infarction have been reported in patients receiving Taxol, highlighting the need for careful monitoring of cardiac function during and after treatment 3, 6.

Patient Monitoring and Risk Factors

• Patients with high-risk features, such as diabetes mellitus, hypertension, prior radiotherapy to the chest wall, performance status of 2, and age > 60 years, are more likely to develop cardiotoxicity from Taxol 7.
• Regular monitoring of cardiac function, including echocardiography, is recommended for patients receiving Taxol, especially those with high-risk features 7.
• Physicians should be alert to potential cardiac toxicities associated with Taxol and maintain a high degree of caution when administering the drug to patients with cardiac risk factors 4, 6.