PracticeUpdate: Haematology & Oncology

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Interventions for
preventing cardiomyopathy
due to anthracyclines
By Reshma Mahtani, DO
Anthracyclines are commonly used
for the treatment of breast cancer.
Dose-dependent risks of cardiotox-
icity and congestive heart failure are well-
known. Risk factors for the development
of cardiotoxicity have been investigated
and include cumulative dose greater than
>300 mg/m2; age >65 years; history of hy-
pertension, diabetes, or hyperlipidaemia;
lifestyle factors such as smoking and obe-
sity; history of prior radiation involving the
chest; and the use of trastuzumab. Recent
research has focused on early monitoring
and risk stratification. The aim is to iden-
tify patients at higher risk for the develop-
ment of cardiotoxicity based on the use of
biochemical markers and the prophylactic
use of cardio-protectants.
The current article is a systematic review of
16 randomised controlled trials evaluating
the primary prevention of anthracycline-as-
sociated toxicity with the use of various
agents. The authors indicate that “moder-
ate quality data suggest that dexrazoxane,
and low quality data suggest angiotensin
antagonists are likely to be effective for
cardiotoxicity prevention.” The presented
data are not an overwhelming endorsement
of any specific approach. It is interesting to
note that, despite the identification of risk
factors, some patients with little exposure
and no risk factors can develop considera-
ble cardiac damage while others with higher
exposure and risk factors do not develop
any problems. This suggests a possible role
of genetic susceptibility. A large number
of polymorphisms have been reported in
genes that mediate the metabolism, trans-
port, and pharmacological activity of doxo-
rubicin. The clinical significance of these
findings is still under investigation, but may
be the key to identifying patients at most
risk. Once these patients are identified,
the use of cardio-protectants such as ACE
inhibitors, angiotensin-receptor blockers,
and beta blockers may be used as part of
an individualised plan for the prevention of
anthracycline-induced cardiotoxicity.
Dr Mahtani is Assistant
Clinical Professor of the
Division of Hematology/
Oncology at the Sylvester
Comprehensive Cancer
Center, University of Maimi.
Interventions for preventing cardiomyopathy due to
anthracyclines: a Bayesian Network meta-analysis
Ann Oncol 2016 Dec 26;[EPub Ahead of Print], H Abdel-Qadir, G Ong, R Fazelzad, et al
Take-home message
• This systematic review used a Bayesian network meta-analysis to examine the
effects of interventions to prevent cardiomyopathy in adult cancer patients treated
with anthracyclines. A total of 16 randomised controlled trials including 1918 patients
were identified for inclusion; these examined the use of dexrazoxane, beta blockers,
angiotensin antagonists, beta blockers with angiotensin antagonists, prenylamine,
N-acetylcysteine, coenzyme Q10, and statins. Only dexrazoxane treatment was
demonstrably superior to placebo in reducing total cardiotoxicity events (pooled OR,
0.26), with 33% probability of being the most effective agent. When a single outlying
study was removed, angiotensin antagonists had an 84% probability of being the
most effective agent. When heart failure alone was considered, the dexrazoxane and
angiotensin antagonists had odds ratios of 0.12 and 0.18, respectively. No evidence
was found for increased risk of death or for effects on malignancy response rate with
dexrazoxane or angiotensin antagonists.
• This systematic review and meta-analysis found that dexrazoxane (based on moderate-
quality data) and angiotensin antagonists (based on low-quality data) are potentially
effective in preventing cardiotoxicity associated with anthracycline treatment.
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EDITOR’S PICKS 5
VOL. 2 • NO. 1 • 2017