Study: Nearly 20 years on, no adverse impacts for pediatric cancer patients treated with dexrazoxane

Research shows that these children have healthier hearts than those who did not receive dexrazoxane and proves the safety and efficacy of the drug

BUFFALO, NY – The delicate balance between using powerful drugs to cure cancer and reducing damage to healthy tissue is all the more important when the cancer patient is a child. In many cases, chemotherapy to cure the cancer is supplemented with drugs designed to curb the potential damage chemotherapy can cause, either in the short term or later when the patient is an adult.

A new study published in Cancer and authored by researchers from multiple institutions, including the University at Buffalo, shows that dexrazoxane, which is administered to pediatric cancer patients to curb the cardiotoxicity of an important chemotherapy drug, does not adversely affect these patients. , even nearly 20 years later.

Lead author on the paper is Eric J. Chow, MD, of the Fred Hutchinson Cancer Research Center.

The paper examined long-term outcomes in children newly diagnosed with cancer who had participated in clinical trials focused on dexrazoxane. The median time since cancer diagnosis was 18.6 years.

“The long-term effects of dexrazoxane had not been established before, due to the short time it has been in clinical practice since the late 1990s,” said Steven E. Lipshultz, MD, senior author of the paper and A. Conger Goodyear Professor and Chair of Pediatrics at the Jacobs School of Medicine and Biomedical Sciences at the UB. “This is why this article is so important, because it examines these long-term effects of dexrazoxane for the first time.”

In preclinical models, Lipshultz and colleagues had previously found that dexrazoxane was the most consistent cardioprotective agent, a finding that was subsequently confirmed in their clinical studies.

The new study included 1,308 newly diagnosed cancer patients who participated in National Cancer Institute-supported clinical trials in 167 institutions around the world between 1996 and 2001. All the children in these studies received the chemotherapeutic drug doxorubicin, which is known to cause damage to the heart. Some of them were randomized to receive dexrazoxane before each dose of doxorubicin. The aim was to determine whether dexrazoxane reduced chemotherapy-related heart damage without compromising the cancer-fighting effects of the chemotherapy.

‘Hidden wounds’

“Cancer shaped these survivors, but it doesn’t define them,” said Lipshultz, who is also president of UBMD Pediatrics and counselor at Roswell Park Comprehensive Cancer Center. “For these survivors, these late treatment effects are hidden wounds that they will have to deal with for the rest of their lives. The chemotherapeutic drugs they used years ago can cause premature heart failure or other heart problems. It is becoming critical to pre-treat the health problems that may arise years or even decades later.”

The study found that dexrazoxane was not associated with relapse of the first cancer, second cancers, all-cause mortality, or cardiovascular mortality. Among randomized patients treated with dexrazoxane, serious cardiovascular outcomes such as cardiomyopathy, ischemic heart disease and stroke occurred in only 5.6% of patients versus 17.6% of patients not treated with it.

“With more than 80% of children diagnosed with cancer surviving in the long term, this is one of the most significant advances in pediatrics of the past 50 years,” said Lipshultz, noting that in 1970, only 4% of children were diagnosed with cancer. children with acute lymphoblastic leukemia, the most common childhood malignancy, had an event-free survival of five years.

“As these childhood cancer survivors age in the long term, they experience clinically significant late effects from their cancer and its therapies,” said Lipshultz, who is also medical director of Pediatric Services Business Development at Oishei Children’s Hospital. He added that, other than cancer recurrence, the most common of these effects is cardiovascular, which has the potential to significantly limit the activities of daily living for survivors.

“Cardiovascular disease is the leading non-cancerous cause of death in these children,” he said, “and cardiotoxicity associated with cancer therapies can be ubiquitous, persistent and progressive.

“This research confirms that dexrazoxane is safe and effective for protecting the hearts of pediatric cancer patients from the toxicity of chemotherapeutic drugs even 18 years later,” Lipshultz said. “The goal for these survivors is to allow them to thrive as adults and live productive lives well beyond hospitalization. Hopefully, this will give the survivors the hope and chance for a better future. Thanks to our survival research, we can now ‘start with the end in mind’ by using an effective cardioprotective treatment.”

Lipshultz and Chow are the co-principal investigators of the multicenter National Cancer Institute grant that funded this study. Co-authors on the paper are from the Dana-Farber Cancer Institute; Children’s Hospital of Philadelphia; Wayne State University; City of Hope; University of Alabama at Birmingham; Golisano Children’s Hospital; Children’s Hospital Los Angeles; the University of Arizona, Tucson; and Children’s Wisconsin.

The work was funded by the National Institutes of Health; St Baldrick’s Foundation; the Leukemia and Lymphoma Society; Sofia’s Hope Inc.; and the American Lebanese Syrian Associated Charities.