August 6, 2026Journal of Clinical Oncology
Longitudinal Change in Cardiac Function After Doxorubicin and Dexrazoxane: A Report From Children's Oncology Group ALTE11C2
Key result
Dexrazoxane before doxorubicin cuts 5-year risk of reduced LV function ~46% in childhood cancer survivors.
- HR 0.54
- 95% CI 0.31-0.93
- n=895
Why the study?
Whether the cardioprotective association of dexrazoxane with preserved LV systolic function persists in larger populations over time and its impact on cardiomyopathy screening recommendations remained unclear.
Does dexrazoxane preserve left ventricular systolic function in childhood cancer survivors receiving doxorubicin?
Key Points
- This research aims to assess the long-term effects of dexrazoxane on left ventricular function in childhood cancer survivors treated with doxorubicin.
- Analyzed echocardiographic data from participants enrolled in multiple Children's Oncology Group protocols.
- Conducted up-front 1:1 random assignment for dexrazoxane prior to doxorubicin treatment.
- Used generalized estimating equations and Cox proportional hazard models to estimate differences and associations.
- Preserved left ventricular systolic function was noted in patients treated with dexrazoxane (z-score difference 0.4 [95% CI, 0.2 to 0.5]).
- Dexrazoxane was linked to decreased hazards of reduced left ventricular function at 1 year (0.58 [95% CI, 0.41 to 0.82]) and 5 years (0.54 [95% CI, 0.31 to 0.93]).
- The incidence of reduced left ventricular function in high-risk groups decreased significantly, from 40 to 21.8 events/1,000 person-years (P = .001).
Study Design
Type
RCT (n=895)
Blinding
Blinded central remeasurements
Randomization
1:1
Multicenter
Yes
Structured PICO
Does dexrazoxane preserve left ventricular systolic function in childhood cancer survivors receiving doxorubicin?
P
Population
895 childhood cancer survivors treated with doxorubicin (median dose 360 mg/m2), 51% of whom received dexrazoxane, followed for a mean of 5.9 years.
I
Intervention
Dexrazoxane administered uniformly as an intravenous bolus before doxorubicin (10:1 mg/m2 dexrazoxane:doxorubicin dose).
C
Comparator
Doxorubicin without dexrazoxane.
O
Outcome
Preservation of left ventricular (LV) systolic function (measured by z-score difference).surrogate
Main Result
Hazard Ratio: 0.54 (95% CI 0.31–0.93)
Dexrazoxane provides long-term cardioprotection against doxorubicin-induced left ventricular systolic dysfunction in childhood cancer survivors, potentially reducing the need for intensive cardiomyopathy screening.
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Now that we've established there's this benefit, and the majority of cancer patients do receive this drug, we will hopefully be able to decrease the frequency of their echocardiograms as they age, although we need to keep studying these survivors to better understand how their cardiovascular health changes as they enter their 50s and 60s. It could give patients and their families a little bit of a piece of mind. It's what makes me want to get out of bed and do cancer research every day.”
“Among young adult aged survivors of childhood cancer, dexrazoxane was associated with a cardioprotective effect nearly 20 years after initial anthracycline exposure.”
Implication
Supports long-term LV preservation with dexrazoxane in survivors; leaves open whether screening recommendations can be safely modified.
Abstract
PURPOSE Dexrazoxane has been associated with preservation of left ventricular (LV) systolic function in relatively small studies of long-term childhood cancer survivors. What remains less clear is whether this association is also seen in larger populations over time and what effect dexrazoxane has on cardiomyopathy screening recommendations. METHODS We analyzed echocardiographic data from participants who received doxorubicin treatment and were enrolled on Children's Oncology Group protocols P9404, P9425, P9426, P9754, and Dana Farber Cancer Institute protocol 95-01. Except for P9754, all protocols featured up-front 1:1 random assignment with dexrazoxane administered uniformly as an intravenous bolus before doxorubicin (10:1 mg/m 2 dexrazoxane:doxorubicin dose). Blinded central echocardiogram remeasurements were used when possible; otherwise, data were abstracted from institutional reports. Differences and associations by ± dexrazoxane were estimated using generalized estimating equations and Cox proportional hazard models, adjusting for age, sex, doxorubicin dose, chest radiotherapy, and echocardiogram data type. RESULTS Among 895 patients (mean follow-up, 5.9 years, 230 with ≥10-year follow-up; median doxorubicin dose, 360 mg/m 2 ; 51% dexrazoxane-exposed) with evaluable echocardiograms (n = 2,279; 1,581 centrally remeasured; 698 report only), preserved LV systolic function was observed in patients treated with dexrazoxane (z-score difference 0.4 [95% CI, 0.2 to 0.5]) versus without. Dexrazoxane was also associated with decreased hazards of reduced LV function (fractional shortening <30% or ejection fraction <50%) occurring after 1 (0.58 [95% CI, 0.41 to 0.82]) and 5 years (0.54 [95% CI, 0.31 to 0.93]) postdiagnosis. Finally, dexrazoxane appeared to decrease the incidence of reduced LV function among those classified by current cardiomyopathy screening guidelines as high risk to rates like a lower-risk group (from 40 to 21.8 events/1,000 person-years; P = .001). CONCLUSION Dexrazoxane exerts a significant doxorubicin cardioprotective effect on LV systolic function long term and may reduce screening needs.
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Cite This Study
Mobley et al. (2026) conducted an RCT in Childhood cancer treated with doxorubicin (n=895). Dexrazoxane vs. Doxorubicin without dexrazoxane was evaluated on Reduced LV function (fractional shortening <30% or ejection fraction <50%) at 5 years postdiagnosis (HR 0.54, 95% CI 0.31-0.93). Dexrazoxane administered before doxorubicin in childhood cancer survivors significantly decreased the hazard of reduced left ventricular function at 5 years postdiagnosis (HR 0.54; 95% CI 0.31-0.93).