Dexrazoxane and Long-Term Heart Function in Survivors of Childhood Cancer.

2023

2248-2257

04/2023

1527-7755

PURPOSE: For survivors of childhood cancer treated with doxorubicin, dexrazoxane is cardioprotective for at least 5 years. However, longer-term data are lacking.

METHODS: Within the Children's Oncology Group and the Dana Farber Cancer Institute's Childhood Acute Lymphoblastic Leukemia Consortium, we evaluated four randomized trials of children with acute lymphoblastic leukemia or Hodgkin lymphoma, who received doxorubicin with or without dexrazoxane, and a nonrandomized trial of patients with osteosarcoma who all received doxorubicin with dexrazoxane. Cumulative doxorubicin doses ranged from 100 to 600 mg/m across these five trials, and dexrazoxane was administered uniformly (10:1 mg/m ratio) as an intravenous bolus before doxorubicin. Cardiac function was prospectively assessed in survivors from these trials, plus a matched group of survivors of osteosarcoma treated with doxorubicin without dexrazoxane. Two-dimensional echocardiograms and blood biomarkers were analyzed centrally in blinded fashion. Multivariate analyses adjusted for demographic characteristics, cumulative doxorubicin dose, and chest radiotherapy determined the differences and associations by dexrazoxane status.

RESULTS: From 49 participating institutions, 195 participants were assessed at 18.1 ± 2.7 years since cancer diagnosis (51% dexrazoxane-exposed; cumulative doxorubicin dose 297 ± 91 mg/m). Dexrazoxane administration was associated with superior left ventricular fractional shortening (absolute difference, +1.4% [95% CI, 0.3 to 2.5]) and ejection fraction (absolute difference, +1.6% [95% CI, 0.0 to 3.2]), and lower myocardial stress per B-type natriuretic peptide (-6.7 pg/mL [95% CI, -10.6 to -2.8]). Dexrazoxane was associated with a reduced risk of having lower left ventricular function (fractional shortening < 30% or ejection fraction < 50%; odds ratio, 0.24 [95% CI, 0.07 to 0.81]). This protective association was primarily seen in those treated with cumulative doxorubicin doses ≥ 250 mg/m.

CONCLUSION: Among young adult-aged survivors of childhood cancer, dexrazoxane was associated with a cardioprotective effect nearly 20 years after initial anthracycline exposure.

10.1200/JCO.22.02423

J Clin Oncol

36669148

Late health outcomes after dexrazoxane treatment: A report from the Children's Oncology Group.

2021

2021 Oct 13

1097-0142

<p><strong>BACKGROUND: </strong>The objective of this study was to examine long-term outcomes among children newly diagnosed with cancer who were treated in dexrazoxane-containing clinical trials.</p>

<p><strong>METHODS: </strong>P9404 (acute lymphoblastic leukemia/lymphoma [ALL]), P9425 and P9426 (Hodgkin lymphoma), P9754 (osteosarcoma), and Dana-Farber Cancer Institute 95-01 (ALL) enrolled 1308 patients between 1996 and 2001: 1066 were randomized (1:1) to doxorubicin with or without dexrazoxane, and 242 (from P9754) were nonrandomly assigned to receive dexrazoxane. Trial data were linked with the National Death Index, the Organ Procurement and Transplantation Network, the Pediatric Health Information System (PHIS), and Medicaid. Osteosarcoma survivors from the Childhood Cancer Survivor Study (CCSS; n&nbsp;=&nbsp;495; no dexrazoxane) served as comparators in subanalyses. Follow-up events were assessed with cumulative incidence, Cox regression, and Fine-Gray methods.</p>

<p><strong>RESULTS: </strong>In randomized trials (cumulative prescribed doxorubicin dose, 100-360&nbsp;mg/m ; median follow-up, 18.6&nbsp;years), dexrazoxane was not associated with relapse (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63-1.13), second cancers (HR, 1.19; 95% CI, 0.62-2.30), all-cause mortality (HR, 1.07; 95% CI, 0.78-1.47), or cardiovascular mortality (HR, 1.45; 95% CI, 0.41-5.16). Among P9754 patients (all exposed to dexrazoxane; cumulative doxorubicin, 450-600&nbsp;mg/m ; median follow-up, 16.6-18.4&nbsp;years), no cardiovascular deaths or heart transplantation occurred. The 20-year heart transplantation rate among CCSS osteosarcoma survivors (mean doxorubicin, 377&nbsp;±&nbsp;145&nbsp;mg/m ) was 1.6% (vs 0% in P9754; P&nbsp;=&nbsp;.13). Among randomized patients, serious cardiovascular outcomes (cardiomyopathy, ischemic heart disease, and stroke) ascertained by PHIS/Medicaid occurred less commonly with dexrazoxane (5.6%) than without it (17.6%; P&nbsp;=&nbsp;.02), although cardiomyopathy rates alone did not differ (4.4% vs 8.1%; P&nbsp;=&nbsp;.35).</p>

<p><strong>CONCLUSIONS: </strong>Dexrazoxane did not appear to adversely affect long-term mortality, event-free survival, or second cancer risk.</p>

10.1002/cncr.33974

Cancer

34644414