Recently, an analysis of long-term cardiomyopathy risk in 28,000 childhood cancer survivors in the US and Europe was done. Researchers compared 4 chemotherapy drugs with development of cardiomyopathy (diseases of the heart muscle). They found exposure to different anthracyclines results in different long-term cardiovascular risk.

Heart disease is a leading cause of early death from non-cancer causes in long-term survivors of childhood cancer.

Exposure to anthracycline chemotherapies, such as doxorubicin, has long been associated with an increased risk of cardiovascular disease in long-term childhood cancer survivors,” said Dr Gregory Aune, assistant professor of paediatric hematology-oncology at UT Health San Antonio and an investigator with the university’s Greehey Children’s Cancer Research Institute

This research indicates that exposure to different anthracyclines results in variable long-term cardiovascular risk. In the future, it will be important to take these differences into account when screening long-term survivors for cardiovascular complications and in the development of modern treatment regimens.”

“The past several decades have been focused on devising combinations of drugs that work best for curing patients,” said Dr Gail Tomlinson, professor of paediatrics, division director of paediatric haematology-oncology, and holder of the Greehey distinguished chair in genetics and cancer at UT Health San Antonio.

This has been a highly successful process with a substantial increase in survival for most cancer types. Now with so many survivors alive many years from their original cancer, it is imperative to fine-tune protocols based on the goal of minimising late effects.”

Main Outcomes and Measures

Cardiomyopathy (severe, life-threatening, or fatal) by 40 years of age. Agent-specific Cox proportional hazards models evaluated cardiomyopathy risk, adjusting for chest radiotherapy, age at cancer diagnosis, sex, and exposure to anthracyclines or to an anthraquinone. An agent-specific cardiomyopathy equivalence ratio (relative to doxorubicin) was estimated for each dose category as a ratio of the hazard ratios, and then a weighted mean determined the overall agent-specific equivalence ratio across all dose categories.

Conclusions and Relevance

In a large data set assembled to examine long-term cardiomyopathy risk in childhood cancer survivors, daunorubicin was associated with decreased cardiomyopathy risk vs doxorubicin, whereas epirubicin was approximately isoequivalent. By contrast, the current hematologic-based doxorubicin dose equivalency of mitoxantrone (4:1) appeared to significantly underestimate the association of mitoxantrone with long-term cardiomyopathy risk.

Co-authors of the study are from the Netherlands; the Fred Hutchinson Cancer Research Centre in Seattle; St Jude Children’s Research Hospital in Memphis; the Duke University School of Medicine; and the University of Washington-Seattle.

Authors
Elizabeth AM Feijen, Wendy M Leisenring, Kayla L Stratton, Kirsten K Ness, Helena JH van der Pal, Elvira C van Dalen, Gregory T Armstrong, Gregory J Aune, Daniel M Green, Melissa M Hudson, Jacqueline Loonen, Kevin C Oeffinger, Leslie L Robison, Yutaka Yasui, Leontien CM Kremer, Eric J Chow

University of Texas Health Science Centre San Antonio material
JAMA Oncology abstract

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