Cardiotoxicity of Cancer Chemotherapy

Abstract

Many children and adolescents with cancer receive chemotherapeutic agents that are cardiotoxic. Thus, while survival rates in this population have improved for some cancers, many survivors may experience acute or chronic cardiovascular complications that can impair their quality of life years after treatment. In addition, cardiac complications of treatment lead to reductions in dose and duration of chemotherapy regimens, potentially compromising clinical efficacy. Anthracyclines are well known for their cardiotoxicity, and alkylating agents, such as cyclophosphamide, ifosfamide, cisplatin, busulfan, and mitomycin, have also been associated with cardiotoxicity. Other agents with cardiac effects include vinca alkaloids, fluorouracil, cytarabine, amsacrine, and asparaginase and the newer agents, paclitaxel, trastuzumab, etoposide, and teniposide. The heart is relatively vulnerable to oxidative injuries from oxygen radicals generated by chemotherapy. The cardiac effects of these drugs include asymptomatic electrocardiographic abnormalities, blood pressure changes, arrhythmias, myocarditis, pericarditis, cardiac tamponade, acute myocardial infarction, cardiac failure, shock, and long-term cardiomyopathy. These effects may occur during or immediately after treatment or may not be apparent until months or years after treatment. Mild myocardiocyte injury from chemotherapy may be of more concern in children than in adults because of the need for subsequent cardiac growth to match somatic growth and because survival is longer in children. Primary prevention is therefore important. Patients should be educated about the cardiotoxic risks of treatment and the need for long-term cardiac monitoring before chemotherapy is begun. Cardiotoxicity may be prevented by screening for risk factors, monitoring for signs and symptoms during chemotherapy, and continuing follow-up that may include electrocardiographic and echocardiographic studies, angiography, and measurements of biochemical markers of myocardial injury. Secondary prevention should aim to minimize progression of left ventricular dysfunction to overt heart failure. Approaches include altering the dose, schedule, or approach to drug delivery; using analogs or new formulations with fewer or milder cardiotoxic effects; using cardioprotectants and agents that reduce oxidative stress during chemotherapy; correcting for metabolic derangements caused by chemotherapy that can potentiate the cardiotoxic effects of the drug; and cardiac monitoring during and after cancer therapy. Avoiding additional cardiotoxic regimens is also important in managing these patients. Treating the adverse cardiac effects of chemotherapy will usually be dependent on symptoms or will depend on the anticipated cardiovascular effects of each regimen. Treatments include diuresis, afterload reduction, beta-adrenoceptor antagonists, and improving myocardial contractility.

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

“…• Introduction of extended-field high-dose (35)(36)(37)(38)(39)(40)(41)(42)(43)(44) The types of chemotherapy-induced cardiovascular alterations reported primarily, but not exclusively, in adults include the following: Acute cardiac rhythm abnormalities (arrhythmias including QT prolongation), myocardial ischemia or infarction, hypertension, and significant left ventricular (LV) contractile dysfunction. 37,38 The pathogenesis of these diverse cardiovascular effects varies and may involve multiple mechanisms.…”

“…37,38 The pathogenesis of these diverse cardiovascular effects varies and may involve multiple mechanisms.…”

“…[40][41][42][43] Paclitaxel has been used to treat breast and ovarian cancer in adults and has been suggested for use in children. 38 Paclitaxel may induce bradycardia directly through actions on the Purkinje system or indirectly through its formulation vehicle, Cremophor EL (polyoxyethylated castor oil). When used in combination, paclitaxel appears to enhance doxorubicin cardiotoxicity by altering doxorubicin pharmacokinetics and increasing the myocyte formation of doxorubicinol, the major metabolite of doxorubicin.…”

Long-term cardiac effects of treatment for childhood leukemia

“…Long-term cardiac complications may occur several years after completion of anticancer treatment [1][2][3][4][5][6]. In the past year report from the Childhood Cancer Survivor Study (the largest cohort of childhood cancer survivors in the world) showed that survivors of childhood cancers are five to ten times more likely than their healthy siblings to develop heart disease even 30 years after diagnosis -such as congestive heart failure, myocardial infarction, pericardial disease, valvular heart disease [2].…”

Screening for Long-Term Cardiac Status During Cancer Treatment

“…[13][14][15][16] Early-onset cardiotoxicity occurs within 1 year after therapy, 14,15,[17][18][19][20] and late-onset cardiotoxicity occurs >1 year after anthracycline therapy. 14,15,[18][19][20] Thus, the report by Sawaya et al 7 is limited to predicting early-onset cardiotoxicity. As it may not be long enough for clinically relevant events to develop, the utility for predicting events in this short period is unknown.…”