Not all chemotherapies linked to equal long-term CVD risk
Some chemotherapy drugs may be associated with higher risk of cardiomyopathy later in life than others, according to a new study.
In a multicentre cohort study of 28,423 childhood cancer survivors (survival ≥5 years), researchers from the US and the Netherlands compared late-onset cardiomyopathy outcomes (defined as severe, life-threatening or fatal cardiomyopathy by 40 years of age) among 14,356 individuals who had been exposed to one of five commonly used cancer treatment agents: anthracyclines doxorubicin, daunorubicin, idarubicin or epirubicin, or the anthraquinone mitoxantrone.
“Anthracyclines are part of many effective paediatric cancer treatment protocols. Most paediatric oncology treatment groups assume that the hematologic toxicity of anthracycline agents is equivalent to their cardiotoxicity,” said the authors. “For example, Children’s Oncology Group substitution rules consider daunorubicin and epirubicin isoequivalent to doxorubicin, whereas mitoxantrone and idarubicin are considered 4 –5 times as toxic as doxorubicin.”
After a median follow-up of 20 years (range 5-40 years) following receipt of a cancer diagnosis, 399 cases of cardiomyopathy—defined as abnormal heart muscle with impaired function—were identified among the five treatment groups. Using doxorubicin as a baseline, the researchers compared the dose-equivalent cardiomyopathy risks of the other four drugs.
Compared with the doxorubicin group (n=9,330), the daunorubicin group was associated with decreased risk of cardiomyopathy (n=4,433; equivalence ratio [ER] 0.6, 95% confidence interval [CI] 0.4–1.0). Epirubicin had a similar risk to doxorubicin (n=342; ER 0.8, 95% CI 0.5–2.8), while mitoxantrone had a much higher risk than estimated (n=265; ER=10.5, 95% CI 6.2–19.1). Idarubicin had too few cardiomyopathy outcomes for the team to make a specific estimate. [JAMA Oncol 2019; doi:10.1001/jamaoncol.2018.6634]
Cumulative dose data of each agent, as well as chest radiotherapy exposures were obtained from medical records from a combination of three studies: the Childhood Cancer Survivor Study (treated between 1970-1999, 20,367 patients), the Dutch Childhood Oncology Group LATER study (diagnosed between 1963-2001, 5,741 patients), and the St Jude Lifetime study (treated between 1962-2005, 2,315 patients).
"Exposure to anthracycline chemotherapies has long been associated with an increased risk of cardiovascular disease (CVD) in long-term childhood cancer survivors," said Dr Gregory Aune, study co-author and paediatric oncologist at the University of Texas Health Science Center (UT Health), San Antonio, US. "Previously, it was assumed that exposure to any [anthracycline] carried the same risk… this research indicates that exposure to different anthracyclines results in variable long-term CV risk.”
Aune added that these differences would need to be taken into account when screening long-term survivors for CV complications, as well as in developing 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, division director of paediatric haematology-oncology 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 minimizing late effects."