Exposure to dexrazoxane among pediatric patients with leukemia or lymphoma did not affect overall mortality during a median follow-up period of 12.6 years, according to a report published online in the Journal of Clinical Oncology.
Aggregated data from three Children’s Oncology Group trials showed that among 1,008 pediatric patients who received treatment with doxorubicin with or without dexrazoxane (DRZ) from 1996 to 2001, exposure to DRZ was not associated with an increased risk of relapse (HR, 0.81; 95% CI, 0.60-1.08) or death (HR, 1.03; 0.73-1.45). Comparing DRZ with non-DRZ treatment groups at 10 years, the cumulative incidence of relapse was 16.1% vs. 19.1% (difference, – 3.0%; 95% CI, – 7.9% to 0.2%) and overall mortality was 12.8% vs. 12.2% (difference, – 0.6%; 95% CI, – 3.5% to 4.7%). The three trials (P9404, P9425, and P9426) evaluated individually likewise did not show significant differences in relapse or mortality rates.
Although studies in adults show a positive effect of DRZ on heart failure rates after anthracycline therapy, concern over DRZ interference with cancer therapies and a possible link to second cancers have limited its use in children and prompted Dr. Eric Chow of the Fred Hutchinson Cancer Research Center, Seattle, and his colleagues to assess the effect of DRZ on mortality.
The investigators wrote that DRZ “does not appear to interfere with cancer treatment efficacy, in terms of original cancer mortality or overall risk of relapse. Although the risk for secondary cancer mortality (mainly as a result of AML/MDS [acute myeloid leukemia/myelodysplastic syndrome]) was greater among those exposed to DRZ, the overall number of events was small, and the differences were not statistically significant,” the investigators said. (J. Clin. Oncol. 2015 May 26 [doi:10.1200/JCO.2014.59.4473])
Aggregated data from the three trials shows that the 10-year mortality rate of AML/MDS was 1.4% for those treated with DRZ (seven patients), compared with 0.8% for those treated without DRZ (five patients).
The beneficial effects of DRZ in decreasing the risk of heart failure have been observed in trials of adult patients, but the results for survivors of childhood cancers have been inconclusive because heart failure may develop over a longer time period in children. With the median age of survivors in this study of 24 years, significant differences in cardiac mortality due to DRZ use are not detectable. To evaluate DRZ as a cardioprotectant, a new Children’s Oncology Group study (Effects of Dexrazoxane Hydrochloride on Biomarkers Associated With Cardiomyopathy and Heart Failure After Cancer Treatment [HEART]) will determine the cardiovascular health of individuals in the three trials P9404, P9425, and P9426.
“Given that second cancers and symptomatic cardiac disease appear to be by far the two most common categories of serious late effects (in terms of both absolute and relative risks) among long-term childhood cancer survivors as a group … with cumulative incidences of each approaching 20% by age 50 years, any strategy that offers the promise of reduced cardiotoxicity without being offset by second cancers is highly attractive,” Dr. Chow and his associates wrote.
The study was supported by the National Institutes of Health, St. Baldrick’s Foundation, and the Leukemia and Lymphoma Society. Dr. Chow reported having no relevant financial conflicts. Three of his coauthors reported having financial relationships with industry.