There medication was gradually ceased and she recovered. This

There
are potentially fatal cardiotoxic effects of the chemotherapeutic drug
Doxorubicin. This was described in a 57-year-old woman who presented with heart
failure 17 years after her initial breast cancer treatment, despite lacking
risk factors and good health.

Therapeutically,
Doxorubicin is an anthracycline antibiotic which prevents the growth of solid
and malignant tumours by inducing apoptosis and inhibiting topoisomerase II 1
2.

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Although
the mode of action in terms of cardiotoxicity is not yet fully established, Doxorubicin
damages mitochondria and the enzymes involved in oxidative phosphorylation 3.
After reduction by NADH dehydrogenase, it then reacts with molecular oxygen to
form superoxide radicals, which promote cardiomyocyte apoptosis, particularly
as the heart is prone to oxidative stress 4.
Doxorubicin also suppresses cardiac-specific genes, resulting in decreased contractile
proteins and weakened myocardium 5.

To
target her tumour, the patient underwent 4 cycles of 75mg/m² of Doxorubicin amongst other
treatments including whole-breast radiation. However, at the time, no abnormal
cardiac function was reported.

As
an emergency, she suffered acute dyspnoea, tachycardia and hypertension. Laboratory
tests revealed normal cardiac enzymes, but a further echocardiogram indicated low
left ventricular ejection function (LVEF). These findings and her symptoms of
heart failure suggested Doxorubicin Induced Cardiomyopathy, and helped to rule
out myocarditis and obstructive coronary artery disease 6
7 .

Despite
her late presentation, the patient was prescribed a beta-blocker, angiotensin-converting
inhibitor, Digoxin and a diuretic 7. Her LVEF
increased, the medication was gradually ceased and she recovered. This case highlights
the incomplete knowledge of cardiotoxic action of Doxorubicin and questions
whether the chemotherapeutic dosage and longer observation post treatment
should be considered, to reduce and identify such late phase presentations
respectively.

1  Lexicomp
Online. ‘Doxorubicin’ Internet. 2015, cited 30/01/18. Available from: http://chemocare.com/chemotherapy/drug-info/doxorubicin.aspx

2   Thorn C, Oshiro C, Marsh S,
Hernandez-Boussard T, McLeod H, Klein T, et al. ‘Doxorubicin Pathway (Cancer
Cell), Pharmacodynamics’ Internet. 2010 cited 29/01/18. Available from: https://www.pharmgkb.org/pathway/PA165292163

3 Octavia Y, Tocchetti C,
Gabrielson K, Janssens S, Crijns H, Moens A. ‘Doxorubin-induced cardiomyopathy:
From molecular mechanisms to therapeutic strategies’. Journal of Molecular and
Cellular Cardiology Internet. June 2012 cited 30/01/18; 52(6): 1213-1225.
Available from: https://www.sciencedirect.com/science/article/pii/S0022282812001150

4 Volkova M, Russell R.
‘Anthracycline Cardiotoxicity: Prevalence, Pathogenesis and Treatment’. Current
Cardiology Review Internet. November 2011 cited 31/01/18; 7(4): 214-220.
Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322439

5 Chatterjee K, Zhang J, Honbo N, Karliner
J. ‘Doxorubin Cardiomyopathy’. Cardiology Internet. Jan 2010 cited
31/01/18; 115(2): 155-162. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848530/

6 Florescu M, Cinteza M, Vinereanu D.
‘Chemotherapy-induced Cardiotoxicity’. Maedica Internet. March 2013 cited
31/01/18; 8(1): 59-67. Available from:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749765

7 No author given. ‘Cardiotoxicity and
Cardiomyopathy’ Medications that may be described by your doctor Internet
Copyright 2018 cited 31/01/18. Available from: http://chemocare.com/chemotherapy/side-effects/cardiotoxicity-and-
cardiomyopathy.aspx