The Impact of Using Nicorandil for the Prevention of Doxorubicin-Induced Cardiotoxicity

Breast cancer is one of the world's most common cancers in females. Most of the chemotherapy protocols used to treat breast cancer involve doxorubicin. Doxorubicin has a very significant antitumor effect on breast tumors. One of the obstacles that hinders the use of doxorubicin is cardiotoxicity. Although many agents are used to address this issue, only dexrazoxane is FDA-approved. One suggested pathway for doxorubicin-induced cardiotoxicity is due to calcium imbalance. Calcium ions are very important in controlling the heart's function. Nicorandil is an anti-anginal agent that shows cardioprotective effects against doxorubicin-induced cardiotoxicity in preclinical trials. Not only that, but preclinical studies on rats and mice have also shown that it has antitumor and augmenting effects on doxorubicin's anticancer properties. Here in our trial, the impact of the nicorandil will be assessed on breast cancer patients. The chosen method will be a parallel, open-label, randomized clinical trial. The selected sampling method will be stratified blocks based on radiotherapy and HFA-ICOS baseline scores. The sample size will be 146 patients, who will be randomized using a premuted block. The primary parameter will be the ejection fraction. The secondary parameters will include cardiac troponins, creatine kinase myocardial band, safety assessment of nicorandil use on the gastrointestinal and cardiovascular systems, quality of life after nicorandil use, cost-effectiveness and cost-utility of nicorandil, and the quality of life and baseline cardiac scoring system.

Inclusion criteria * 18 years - 65 years * Female patients with stage (I, II, III) breast cancer. * Left ventricular ejection fraction (LVEF) ≥ 55% upon breast cancer diagnosis. * Systolic blood pressure ≥ 90 mmHg * Estimated glomerular filtration rate (eGFR ≥ 60 mL/min per 1.73 m²). Exclusion criteria * Pregnant and lactating mothers. * Metastatic breast cancer. (stage IV). * Patients are currently using beta-blockers and phosphodiesterase 5 inhibitors. * Patients who require chronic use of aspirin or chronic use of corticosteroids (≥3 months). * Patients who are diagnosed with heart failure, myocardial infarction, stable angina, cardiogenic shock, hypovolemia, or previous coronary revascularization. * Previously treated with anthracyclines. * Previous gastrointestinal bleeding, ulcer, or perforation. * Severe hepatic impairment (ALT, AST ≥ 5 upper limit normal), or diagnosed with clinical evidence of hepatic ascites, encephalopathy, variceal bleeding, decompensated cirrhosis, and acute hepatitis.