In a study reported in the Journal of Clinical Oncology, Eric J. Chow, MD, MPH, and colleagues found that the use of dexrazoxane was associated with long-term protection of heart function in childhood cancer survivors who received doxorubicin for their cancer. According to the study investigators, “For survivors of childhood cancer treated with doxorubicin, dexrazoxane is cardioprotective for at least 5 years. However, longer-term data are lacking.”
Study Details
The study involved patients from four randomized trials within the Children’s Oncology Group and the Dana Farber Cancer Institute’s Childhood Acute Lymphoblastic Leukemia Consortium in which children with acute lymphoblastic leukemia or Hodgkin lymphoma received doxorubicin with or without dexrazoxane, and a nonrandomized trial of patients with osteosarcoma who received doxorubicin with dexrazoxane. Across the five trials, cumulative doxorubicin doses ranged from 100 to 600 mg/m2; dexrazoxane was given uniformly at a 10:1 mg/m2 ratio as an intravenous bolus before doxorubicin. Cardiac function was prospectively assessed in survivors, with two-dimensional echocardiograms and blood biomarkers being analyzed centrally in blinded fashion.
Among young adult–aged survivors of childhood cancer, dexrazoxane was associated with a cardioprotective effect nearly 20 years after initial anthracycline exposure.— Eric J. Chow, MD, MPH, and colleagues
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Key Findings
The analysis included 195 patients with a mean age of 28.8 ± 5.3 years at study participation assessed at 18.1 ± 2.7 years since cancer diagnosis. Among these, 99 received dexrazoxane and 96 did not; the cumulative doxorubicin dose was 297 ± 91 mg/m2.
On multivariate analysis, receipt of dexrazoxane vs no dexrazoxane was associated with improved left ventricular fractional shortening (absolute difference = +1.4%, 95% confidence interval [CI] = 0.3%–2.5%) and ejection fraction (absolute difference = +1.6%, 95% CI = 0.0%–3.2%), as well as lower myocardial stress as indicated by lower levels of B-type natriuretic peptide (BNP; absolute difference = –6.7 pg/mL, 95% CI = –10.6 to –2.8 pg/mL) and N-terminal pro-BNP (absolute difference = –22.1 pg/mL, 95% CI = –34.3 to –9.8 pg/mL). Absolute differences in global longitudinal strain numerically favored dexrazoxane use (–0.8%, 95% CI = –1.7% to 0.1% for endocardial, and –0.8%, 95% CI = –1.5% to 0.0% for myocardial).
Dexrazoxane use was associated with a significantly reduced risk of poor left ventricular function defined as fractional shortening < 30% or ejection fraction < 50% (odds ratio [OR] = 0.24, 95% CI = 0.07–0.81). The reduced risk was primarily observed among patients who had received a cumulative doxorubicin dose of ≥ 250 mg/m2 (OR = 0.19, 95% CI = 0.05–0.76), with no risk reduction observed among those receiving < 250 mg/m2 (OR = 1.17, 95% CI = 0.07–20.35).
The investigators concluded, “Among young adult–aged survivors of childhood cancer, dexrazoxane was associated with a cardioprotective effect nearly 20 years after initial anthracycline exposure.”
Dr. Chow, of Fred Hutchinson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute, St. Baldrick’s Foundation, and Leukemia and Lymphoma Society. For full disclosures of the study authors, visit ascopubs.org.
