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Dexrazoxane may reduce, prevent cardiotoxicity in childhood cancer survivors
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The cardioprotective agent dexrazoxane may reduce the risk for long-term cardiotoxic events in pediatric, adolescent and young adult patients with cancer treated with anthracycline chemotherapy, according to the results of a systematic review.
Childhood cancer survival rates have risen over the course of several decades, with many patients living into adulthood. However, survival increases have been accompanied by an increased risk for long-term treatment-related adverse events, including cardiotoxicity.
“[T]he price of treatment for childhood cancer for many survivors is persistent, often progressive, and pervasive cardiotoxicity for those treated with anthracycline chemotherapy,” Steven Lipshultz, MD, FAAP, FAHA, chair of pediatrics at Wayne State University School of Medicine and pediatrician-in-chief at Children’s Hospital of Michigan, said in a press release.
Anthracycline-based chemotherapies — including doxorubicin, daunorubicin and epirubicin — are frequently used in the treatment of pediatric hematologic cancers and solid tumors. These chemotherapies are associated with cardiotoxic adverse events, including cardiomyopathy, heart failure, myocardial infarction, conduction defects, valve disease, pericardial disease and hypertension.
Lipshultz and colleagues conducted a literature review and found that a high cumulative dose of anthracyclines served as the most relevant risk factor for long-term cardiotoxicity among survivors of childhood cancer.
Patients treated with a cumulative dose greater than 300 mg/m2 had an 11-fold increased risk for cardiotoxicity, although cardiotoxicity can occur in patients treated with cumulative doses lower than 240 mg/m2.
Concomitant mediastinal or cranial radiation also served as a risk factor for cardiotoxicity.
The researchers identified nonmodifiable risk factors for cardiotoxicity — such as genetic predisposition, pre-existing cardiovascular disease, family history of premature cardiovascular disease and younger age at diagnosis — as well as modifiable risk factors, such as physical inactivity, hypertension, diabetes, obesity and smoking.
Lipshultz and colleagues identified dexrazoxane as a potential cardioprotective agent for use in pediatric, adolescent and young adult patients.
“[Dexrazoxane] is believed to chelate iron and, therefore, interferes with iron-mediated free radical generation, ultimately decreasing tissue damage caused by anthracyclines,” Lipshultz and colleagues wrote.
Dexrazoxane was initially approved for the prevention of cardiac toxicity in women with breast cancer. Since that time, researchers have conducted studies of the agent in pediatric populations.
“[D]exrazoxane is cardioprotective without decreasing the effectiveness of anthracyclines or compromising EFS,” Lipshultz and colleagues wrote. “Its use as a cardioprotectant among children and adolescents has been approved by the American Heart Association and the American Academy of Pediatrics.”
Based on the available data, the researchers recommended the concomitant administration of dexrazoxane in children, adolescents and young adults receiving anthracycline treatment.
“Chemotherapy-related heart damage can be ameliorated or prevented by the drug dexrazoxane, when given immediately before each anthracycline dose,” Lipshultz said. “If implemented, more children with cancer who are treated with anthracyclines may be cured of their malignancy and with less chemotherapy-associated toxicity and late effects.” – by Cameron Kelsall
Disclosures: The researchers report no relevant financial disclosures.
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