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Table 1 Cancer therapeutic agents, risk factors, mechanisms, and manifestations of cardiotoxicity

From: Understanding cardiovascular injury after treatment for cancer: an overview of current uses and future directions of cardiovascular magnetic resonance

Therapeutic agent

Therapeutic indications

Risk factors

Mechanisms

Manifestations of cardiotoxicity

Anthracyclines

Doxorubicin

Breast cancer

Concurrent chemotherapy

Cellular apoptosis induction

Early

Daunorubicin

Gastric

Dosing schedules

ETC. uncoupling

CHF/LV dysfunction

Epirubicin

Leukemias

Elderly

Iron complexation

Myocardial ischemia/infarction

Idarubicin

Lung cancer

Women

Lipid peroxidation of myocyte

Pericarditis/myocarditis

 

Lymphomas

Prior radiation

membranes

QT prolongation

Ovarian

IV administration

Nuclear DNA damage

ST-T wave abnormalities

Sarcomas

Underlying CV disease

ROS formation

Late

Cardiomyopathy

CHF/LV dysfunction

Anthraquinolones

Mitoxantrone

AML

Unknown

ROS formation

Arrhythmias

CHF

Breast cancer

Myocardial ischemia/infarction

NHL

Antimetabolites

5-Fluorouracil

Breast cancer

Underlying CV disease

Endothelial cell damage

Arrhythmias

Colorectal cancer

 

Vasospasm

CHF

Pancreatic cancer

  

Myocardial ischemia/infarction

Antimicrotubules

Paclitaxel

Breast cancer

Unknown

Hypersensitivity reaction

Bradyarrhythmias

CHF

Kaposi’s sarcoma

Hypotension

Myocardial ischemia/infarction

Lung cancer

Ovarian cancer

Vinca alkaloids

Leukemias

Unknown

Possible vasospasm

Autonomic neuropathy

Vinblastine

Lymphomas

Hypotension

Vincristine

Nephroblastoma

Myocardial ischemia/infarction

Raynaud’s phenomenon

Alkylating agents

Busulfan

CML

Unknown

Unknown

Arrhythmias

Pericardial effusion

HTN

Pulmonary fibrosis

Cisplatin

Germ cell tumors

Elderly

Coronary artery fibrosis

Early

Lung cancer

Prior mediastinal irradiation

Hypokalemia

CHF

Lymphomas

Use for metastatic testicular

Hypomagnesaemia

Myocardial ischemia/infarction

Ovarian cancer

cancer

 

Late

Sarcomas

Use with cyclophosphamide

Arrhythmias

HTN

LVH

Myocardial ischemia/infarction

Cyclophosphamide

Leukemias

High dose regimens

Endothelial capillary damage

CHF/LV dysfunction

Lymphomas

Prior mediastinal irradiation

Hemorrhagic myocardial necrosis

Various solid tumors

Prior anthracyclines

Hemorrhagic pericarditis

LVH

Ifosfamide

Lymphomas

High dose regimens

Myocardial fiber fragmentation

Arrhythmias

Various solid tumors

Use for lymphomas

CHF

Biological agents

Interferon-α

Leukemias

 

Unknown

Early

Lymphomas

Arrhythmias

Melanoma

Hypertension

Various solid tumors

Late

Cardiomyopathy

Interleukin-2

Melanoma

 

Unknown

Early

RCC

Hypotension (capillary leak syndrome)

Myocarditis

Thrombotic events

Ventricular arrhythmias

Late

Dilated Cardiomyopathy

Hormone-modifying therapy

Androgen-deprivation therapy

Prostate cancer

Men over 65

Development of metabolic

CAD

Underlying CV disease

syndrome

CHF/LV dysfunction

Dyslipidemia

Myocardial ischemia/infarction

Insulin resistance

QT prolongation

Obesity

SCD

Aromatase Inhibitors

Breast cancers

Unknown

Dyslipidemia

CAD

Estrogen receptor (+)

  

CHF/LV dysfunction

Myocardial ischemia/infarction

Miscellaneous

All-trans retinoic acid (Tretinoin)

APL

Unknown

Unknown

Arrhythmias

CHF

Hypotension

Myocardial ischemia/infarction

Pericardial effusions

Arsenic trioxide

AML

Unknown

Hypomagnesaemia

Arrhythmias with QT prolongation

Pericardial effusion

Pentostatin

Hairy cell leukemia

Use with cyclophosphamide

Unknown

Arrhythmias including A-V block

CHF

Myocardial ischemia/infarction

Radiation therapy

 

Various malignancies

Prior high doses of radiation

Fibrosis caused by inflammatory

Early

Underlying CV disease

changes

Pericarditis/Pericardial effusion

Use with anthracyclines

ROS formation

Late

CAD

CHF

Conduction abnormalities

Constrictive pericarditis

Restroctive cardiomyopathy

Valvular defects

Tyrosine-kinase inhibitors

Bevacizumab

Colorectal cancer

Use with anthracyclines

Monoclonal antibody against VEGF

Arterial and venous thromboembolism

HER-2 (−) breast cancer

 

Possible decrease in nitric oxide and

CHF

Lung cancer

 

prostaglandin production

HTN

Imatinib

GIST

Use with anthracyclines

Unclear, but may induce apoptosis in cardiomyocytes

CHF/LV dysfunction

Leukemias

Pericardial effusion

Lapatinib

HER-2 (+) breast cancer

Use with anthracyclines

Inhibits HER-2 and EGFR

LV dysfunction

QT prolongation

Sorafenib

HCC

Use with anthracyclines

Unclear, but may induce apoptosis in cardiomyocytes, or inhibit VEGF and RAF-1

CHF/LV dysfunction

RCC

HTN

Myocardial ischemia/infarction

Thromboembolism

CHF/LV dysfunction

Sunitinib

GIST

Use with anthracyclines

Unclear, but may induce apoptosis in cardiomyocytes and inhibit VEGF

HTN

RCC

Thrombotic events

Trastuzumab

HER-2 (+) breast cancer

Elderly

Defects in HER-2 signaling associated with cardiac contractility

Early

Prior mediastinal irradiation

CHF

Underlying CV disease

Immune-mediated destruction of cardiomyoytes caused by selective binding to HER-2 protein

LV dysfunction

Use with anthracyclines

Late

    

Cardiomyopathy

  1. AML acute myeloid leukemia, APL acute promyelocytic leukemia, CAD coronary artery disease, CHF congestive heart failure, CML chronic myeloid leukemia, CV cardiovascular, EGFR epidermal growth factor receptor, ETC. electron transport chain, GIST gastrointestinal stromal tumor, HCC haptocellular carcinoma, HER human epidermal growth factor receptor 2, HTN hypertension, LV left ventricle, LVH left ventricular hypertrophy, NHL non-Hodgkin’s lymphoma, RCC renal cell carcinoma, ROS reactive oxygen species, SCD sudden cardiac death, VEGF vascular endothelial growth factor.