Dexrazoxane confers long-term cardioprotection after anthracyclines for pediatric cancer
Click Here to Manage Email Alerts
Dexrazoxane appeared to have a cardioprotective effect almost 2 decades after exposure to anthracyclines among a cohort of young adults who survived childhood cancer, according to study results published in Journal of Clinical Oncology.
Researchers primarily observed the effect of dexrazoxane among those treated with cumulative doses of doxorubicin of 250 mg/m² or higher.
Rationale and methods
Dexrazoxane has been shown to provide at least 5 years of cardioprotection for childhood cancer survivors previously treated with doxorubicin; however, data on the long-term effect of the bisdioxopiperazine had been lacking, according to Eric J. Chow, MD, MPH, attending physician at Seattle Children’s Hospital and associate professor of pediatrics at University of Washington School of Medicine, and colleagues.
For this reason, researchers sought to determine the long-term effect of dexrazoxane in mitigating anthracycline-associated cardiotoxicity among a cohort of 195 survivors of childhood cancer. They pooled data from four randomized clinical trials including children with acute lymphoblastic leukemia or Hodgkin lymphoma treated with doxorubicin with or without dexrazoxane, and one trial of children with osteosarcoma who received doxorubicin with dexrazoxane.
Across the five trials, children received dexrazoxane via IV in a 10 mg/m² to 1 mg/m² ratio before doxorubicin, and cumulative doses of doxorubicin ranged from 100 mg/m² to 600 mg/m².
Researchers also prospectively assessed cardiac function among survivors from all five trials, in addition to a matched group of osteosarcoma survivors who received doxorubicin without dexrazoxane.
Median follow-up was 18.1 years.
Results
Results showed an association of dexrazoxane use with superior left ventricular fractional shortening (absolute difference, +1.4%; 95% CI, 0.3-2.5) and ejection fraction (absolute difference, +1.6%; 95% CI, 0-3.2), as well as –6.7 pg/mL (95% CI, –10.6 to –2.8) lower myocardial stress per B-type natriuretic peptide.
Researchers additionally observed an association between dexrazoxane and decreased risk for lower left ventricular function, including a fractional shortening of less than 30% or ejection fraction of less than 50% (OR = 0.24; 95% CI, 0.07-0.81).
The cardioprotective effect appeared most pronounced among those treated with cumulative doses of doxorubicin of 250 mg/m² or more.
Implications
The study provides evidence of measurable long-term cardioprotection with dexrazoxane for children and adolescents with cancer who receive anthracycline-based chemotherapy, Chow and colleagues wrote.
“Per a recently published international consensus guideline, oncology providers should consider administering dexrazoxane to children and adolescents expected to receive 250 mg/m² of cumulative doxorubicin or an equivalent amount of other anthracyclines,” they added.
Perspective
Back to Top
Seth Rotz, MD
Cardiovascular disease is a major contributor to morbidity and mortality among childhood cancer survivors. Anthracycline-induced cardiomyopathy is a major driver of cardiovascular disease among survivors but may take decades to emerge. Clinically, a normal echocardiogram at the end of chemotherapy — or even 5 to 10 years after — does not necessarily ensure that anthracycline cardiomyopathy will not occur.
To date, we have known that dexrazoxane is able to provide some degree of cardioprotection during treatment, and in the first few years after treatment. This is important as decrements in cardiac function during treatment are associated with inferior outcomes in some diseases.
However, until now it was uncertain if dexrazoxane continues to have a protective effect long term. In this study, Chow and colleagues demonstrate the beneficial effects of dexrazoxane at 2 decades after treatment, particularly for patients who received higher doses of anthracyclines. Indeed, based on these data, dexrazoxane should now be the standard of care for any pediatric or young adult patient expected to receive 250 mg/m2 of doxorubicin (or equivalent).
Although these results should have a significant impact on practice, some questions remain. Is dexrazoxane beneficial for those receiving lower doses of anthracyclines? This study may not have had the necessary power to detect a benefit for these patients. Additionally, current guidelines recommend screening echocardiography to detect early changes in cardiac function among children exposed to anthracyclines. Perhaps these guidelines might be liberalized for patients who received dexrazoxane, although data regarding that question does not currently exist.
Regardless, as childhood cancer survivors are expected to live many years after the end of treatment, these data are extremely encouraging that dexrazoxane can decrease the overall burden of cardiovascular disease.
Collapse
Click Here to Manage Email Alerts