Prevention of Doxorubicin-induced Cardiotoxicity in Breast Cancer Patients

ALA effectively inhibits nuclear factor-kappa B with subsequent decreasing pro- inflammatory cytokines production (TNF-α, IL-6) and increasing the release of anti- inflammatory cytokines such as interleukin-10 (FahimehHaghighatdoostabMitraHariri, 2019).

Relying on the antioxidant and anti-inflammatory effect of Alpha lipoic acid confirmed by a variety of studies in vitro and in vivo, ALA is selected to be studied in Egyptian breast cancer patients who will be treated with doxorubicin including regimens.

Aim of the study:

The aim of the current study is to evaluate the efficacy and tolerability of ALA administration and its impact on the occurrence of doxorubicin-induced cardiotoxicity in Egyptian women with breast cancer by evaluation of the following:

• Evaluation of the occurrence of chemotherapy induced cardiotoxicity by;

• Changes in echocardiographic findings and serum levels of pro brain natriuretic peptide (pro-BNP) and cardiac troponins.
• Severity of DIC will be evaluated by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 For Heart Failure.
• Estimation of oxidative stress burden by measurement of MDA.
• Evaluation of ALA safety by:

ALA safety will be monitored and assessed through patient face to face interviews (at the end of each cycle) and phone calls weekly about the occurrence of any of the following side effects: (Ex; insomnia, fatigue, diarrhea, and skin rash).

Patients will be followed up by monitoring of the side effect reporting card (intervention arm)

Inclusion criteria

• Women aged more than 18 years
• Breast cancer diagnosis
• Entering first cycle of chemotherapy containing ATC
• Subject must be willing and able to sign an informed consent

Exclusion criteria

• History of renal (serum creatinine greater than 2.0 mg/ml) or hepatic insufficiency (bilirubin> 3.0 mg/dl or serum albumin < 3.5 g/dl or prothrombin time < 60% in the absence of orally administered anticoagulant therapy or ultrasound signs of chronic liver damage
• History of heart failure
• Baseline LVEF < 50% determined by transthoracic echocardiogram
• Current participation in any other clinical investigation
• History of severe adverse reaction to Alpha lipoic acid
• Concomitant use of Trastuzumab (HER2 positive patients)
• Previous intake of alpha lipoic acid in the previous 3 months
• Women with prior exposure to anthracyclines and neurotoxic agents (Cis-platin, vincristine, paclitaxel, docetaxel, foscarnet, isonicotinic acid hydrazide "INH,", etc.) in the last 6 months.
• Presence of clinical evidence for severe cardiac illness (i.e., angina pectoris and arrhythmias)
• Any condition that contraindicates chemotherapy (i.e., pregnancy, lactation)