Lipshultz Research Expands Effective Uses of Dexrazoxane

By Bill Bruton

The paper is titled “Dexrazoxane and Long-Term Heart Function in Survivors of Childhood Cancer.” 

“Dexrazoxane should be considered as a standard cardioprotectant in children with cancer receiving a cumulative dose of at least 250 mg/m² of doxorubicin,” wrote Jonathan W. Friedberg, MD, editor-in-chief of the Journal of Clinical Oncology, in his commentary about the paper.

“We were pleased with this comment since we specifically targeted perhaps the leading clinical oncology journal, since even though this is a cardiac medication, the providers making decisions to prescribe it are clinical oncologists,” Lipshultz says. “Enhancing its use by oncologists was our objective.”

This study followed 195 survivors of childhood cancer who are nearly 20 years from treatment and who were enrolled on clinical trials featuring dexrazoxane, primarily in the 1990s.

The work has been supported in part by a National Cancer Institute-funded R01 multicenter study performed at 49 institutions throughout the U.S. and Canada that enabled follow-up on the long-term (15 to 20 years) status of dexrazoxane-treated patients.

“The findings reported in this manuscript represent the primary aims of this R01 grant and indicate that there is long-term cardioprotection from dexrazoxane,” Lipshultz says. “Dexrazoxane-treated young adult-aged survivors of childhood cancer who had received the anthracycline chemotherapy doxorubicin were significantly more likely to have preserved left ventricular function and lower myocardial stress compared with the group assigned to doxorubicin alone nearly 20 years after initial anthracycline exposure.”

Lipshultz and Eric J. Chow, MD, of the Fred Hutchinson Cancer Research Center in Seattle, are co-principal investigators on the grant from the National Cancer Institute that supported this study. Chow is also first author on the paper.

“Since the late 1980s, we have been publishing articles that identify the multiple number of cardiac risk factors associated with late cardiotoxicity associated with cancer treatments in long-term cancer survivors,” Lipshultz says. “The mission that we have been pushing over the past nearly four decades is that the successful treatment of cancer is the balance between the oncological cure while minimizing the toxicity and late effects resulting in the highest quality of life for survivors over their lifespans.”

Despite the demonstrated effectiveness of dexrazoxane, there remained a need for data showing the drug’s long-term efficacy.

“This publication represents the longest-term follow-up of a pediatric cardioprotectant therapy that we are aware of for any indication,” Lipshultz says. “To our knowledge, no other study has been able to examine the long-term efficacy of dexrazoxane as a cardioprotectant in children and adolescents treated for cancer. As such, we believe these results have important clinical practice implications given the uncertainty regarding dexrazoxane’s long-term benefit in childhood cancer survivors, especially since their clinically significant cardiotoxicity appears years — if not decades — after initial oncologic therapy.”

The study was conducted within the NCI-sponsored Children’s Oncology Group, and also supported by the NCI-sponsored Dana Farber Cancer Institute’s Childhood ALL Consortium.

Co-authors on the paper are from:

• Children’s Hospital of Los Angeles
• Children’s Hospital of Michigan
• Children’s Hospital of Philadelphia
• Children’s Wisconsin
• City of Hope
• Dana-Farber Cancer Institute
• Golisano Children’s Hospital
• University of Alabama at Birmingham
• University of Arizona
• University of Montreal