Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Heart and Blood Diseases

Symptoms and General Pathology

Substance Related Disorders

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Breast Neoplasms

Cardiotoxicity

Breast Diseases

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Heart Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

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All Drugs and Chemicals

Lipid Regulating Agents

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Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Fenofibrate

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Immunologic Factors

Antineoplastic Agents, Alkylating

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Antibiotics, Antitubercular

Enzyme Inhibitors

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Antimetabolites

22 patients which will receive four cycles of AC regimen (doxorubicin and cyclophosphamide; each cycle is given every 21 day) plus placebo tablets once daily.

22 patients which will receive four cycles of AC regimen (doxorubicin and cyclophosphamide; each cycle is given every 21 day) plus Fenofibrate 160 mg once daily.

It is an approved drug for hypercholesterolemia, It lowers lipid levels by activating peroxisome proliferator-activated receptor alpha (PPARα).

Placebo is made to look exactly like a real drug but is made of an inactive substance.

Placebo

Anthracycline derived chemotherapy used in treatment of breast cancer

Alkylating agent used in treatment of breast cancer

Hagar Dewidar, Instructor

Tarek Mostafa, Professor

This study aims at evaluating the possible safety and efficacy of fenofibrate in attenuating doxorubicin related cardiac toxicity in breast cancer patients.

Breast cancer represents the most frequently diagnosed malignancy and the second most common cause of cancer death worldwide (Sung et al., 2021). In Egypt, breast cancer is the most common malignancy in women, accounting for 38.8% of cancers in this population, with the estimated number of breast cancer cases nearly 22,700 in 2020 and forecasted to be approximately 46,000 in 2050 (Ibrahim et al., 2014).

Doxorubicin (DOX) is a cytotoxic agent that is commonly used for treatment of breast cancer. Despite its effectiveness, doxorubicin is associated with cumulative and potential cardiotoxicity (Rawat et al.,2021).

Although the precise mechanisms whereby DOX induces myocardial injury have not been fully elucidated, it is widely accepted that DOX induces cardiac injury via several mechanisms, including activation of nuclear factor- Kabba B (NF-ĸB), the induction of pro-inflammatory cytokines, the generation of free radicals, the promotion of apoptotic cell death, and the suppression of Endothelial progenitor cells (EPC) mobilization and function, which are typical changes observed in DOX-induced cardiotoxcity (Cardinale et al., 2020).

Peroxisome proliferator-activated receptor-α (PPARα) has been proposed as a key lipid metabolism modulator and regulator of inflammation. There are three isotypes of PPAR (α, β and ȣ) which have distinct but overlapping functions. Fenofibrate, an important PPAR- α agonist, is widely used in in the treatment for hypercholesterolemia and hypertriglyceridemia (Kim and Kim, 2020). Many studies demonstrated the pleiotropic effects of fenofibrate on the heart that afford direct myocardial protection in addition to the lipid-lowering effects through improvement of vascular endothelial function, reducing oxidative stress and increasing endothelial nitric oxide synthase (eNOS) activation (Walker et al., 2012; Jen et al., 2016).

In addition recent animal study showed that fenofibrate decreased the transactivation of Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), activated endothelial nitric oxide synthase (eNOS) and increased nitric oxide (NO) bioavailability, which in turn suppressed MMP-2 (matrix 4 metalloproteinase-2) and MMP-9 (matrix metalloproteinase-9), a well-recognized mediator of adverse ventricular fibrosis and subsequent remodeling, which established the role of fenofibrate against DOX-induced cardiotoxicity in mice (Huang et al., 2021). In addition, it is known that DOX- increases circulating N-terminal pro-B-type natriuretic peptide (NT- pro-BNP) and B-type natriuretic peptide (BNP) that were attenuated by fenofibrate (Huang et al., 2021)

Evaluation of Possible Safety and Efficacy of Fenofibrate in the Prophylaxis of Doxorubicin Induced Cardiotoxicity in Breast Cancer Patients

Clinical Study to Evaluate the Possible Safety and Efficacy of Fenofibrate in the Prophylaxis of Doxorubicin Induced Cardiotoxicity in Breast Cancer Patients

The primary outcome is to avoid decrease in patients ejection fraction while administrating doxorubicin which is known to cause a declination in cardiac ejection fraction threatening of heart failure

The secondary outcome is decrease in serum levels of the measured biological markers which are brain naturetic peptide and myeloperoxidase

Tanta University

Instructor of clinical pharmacy

Spots Global Cancer Trial Database for breast cancer , doxorubicin, fenofibrate , cardiotoxicity