Dexrazoxane May Reduce Cardiotoxicity in Pediatric AML
Use of anthracycline-containing chemotherapy to treat AML in pediatric patients has improved OS, but cardiotoxicity is a risk.
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Dexrazoxane (DEX) was associated with smaller reductions in ejection fraction (EF) during therapy for acute myeloid leukemia (AML) and a lower risk for early LVSD in pediatric patients, according to a presentation at the 2018 ASCO Annual Meeting.
Use of anthracycline-containing chemotherapy regimens to treat AML in pediatric patients has contributed to an improved overall survival (OS) of greater than 65%. However, anthracycline is associated with greater risk of cardiotoxicity. Dexrazoxane, a cardioprotective agent, may reduce this risk, but studies of its effects in pediatric patients with AML are limited.
For the Children's Oncology Group trial AAML1031, DEX was administered at the discretion of the treating physician. At each treatment course, DEX exposure was documented; EF and shortening fraction (SF) values were also recorded after each course and in follow-up, with absolute change in EF from baseline computed for each course. In this study, LVSD was defined as EF less than 50% or SF less than 24% from initiation of frontline therapy through follow-up at 1 year post treatment.
Baseline EF at each course, occurrence of LVSD, and 3-year OS and event-free survival (EFS) were compared for 96 DEX-exposed patients and 918 unexposed patients. Sex, age, race, initial white blood cell count, risk group, and treatment arm were similar across both groups.
In the DEX-exposed group, declines in EF were smaller (range of course-specific median baseline EF, 0 to –4.0 vs 0 to –6.4; all P<.05) and risk for early LVSD was overall lower (6.3% vs 19.2%; RR = 0.33; 95% CI, 0.15-0.72; P=.005) compared with the nonexposed group. The effect of DEX on LVSD risk was particularly pronounced for female patients (RR = 0.16; 95% CI, 0.05-0.65).
Three-year OS (71.9% vs 63.0%; P=.093) and EFS (54.5% vs 44.2%; P=.070) were nonsignificantly higher in the DEX-exposed group vs the unexposed group.
The authors reported that “small numbers may have limited our ability to detect differences in OS and EFS.” They suggest longer follow-up is needed to elucidate the sustained benefit of DEX.
Getz KD, Sung L, Leger K, et al. Effect of dexrazoxane on left ventricular function and treatment outcomes in patients with acute myeloid leukemia: a Children's Oncology Group report. Oral presentation at: 2018 ASCO Annual Meeting; June 1-5, 2018; Chicago, IL.