Cardiac side-effects of cancer chemotherapy

Abstract

The spectrum of cardiac side-effects of cancer chemotherapy has expanded with the development of combination, adjuvant and targeted chemotherapies. Their administration in multiple regimens has increased greatly, including in older patients and in patients with cardiovascular and/or coronary artery disease (CAD). Cardiac toxicity of anthracyclines involves oxidative stress and apoptosis. Early detection combines 2D-echocardiography and/or radionuclide angiography and recent methods such as tissue Doppler imaging, strain rate echocardiography and sampling of serial troponin and/or NT-proBNP levels. Dexrazoxane has proven effective in the prevention of dose-related toxicity in children and adults. High doses of the alkylating drugs cyclophosphamide and ifosfamide may result in a reversible heart failure and in life-threatening arrhythmias. Myocardial ischemia induced by the antimetabolites 5-fluorouracil and capecitabine impacts prognosis of patients with prior CAD. Severe arrhythmias may complicate administration of microtubule inhibitors. Targeted therapies with the antibody-based tyrosine kinases (TK) inhibitors trastuzumab and, to a lesser extent, alemtuzumab induce heart failure or asymptomatic LV dysfunction in 1-4% and 10%, respectively. Cetuximab and rituximab induce hypotension, whereas bevacizumab may promote severe hypertension and venous thromboembolism. Small molecule TK inhibitors may also elicit LV dysfunction, in only few patients treated with imatinib mesylate, but in a substantially higher proportion of those receiving the multitargeted TK inhibitor sunitinib or the recently approved drugs erlotinib, lapatinib and dasatinib. Management of patients at increased cardiovascular risk associated with advancing age, previous CAD or targeted therapies may be optimized by referral to a cardiologist in a cross-specialty teamwork.