Chemotherapy toxicity is continuously increasing due to the constantly growing number of patients treated with chemotherapy, biological drugs and / or radiotherapy, often combined and in cumulative doses, and of cancer survivors. The predisposition to cardiotoxicity depends on genetic factors as well as on individual and
environmental factors (e.g. age and presence of other pathologies, such as ischemic heart disease, hypertension, diabetes, alcohol abuse, smoking).
Cardiotoxicity may occur during therapy or after months or even many years. Most patients have no symptoms and only instrumental tests can demonstrate the damage caused by chemo and / or radiation therapy: arrhythmias, pericardial effusion, reduced contractile function of the left ventricle, up to an evident clinical picture of Dilated cardiomyopathy. More rarely, it presents with congestive heart failure, and even myocardial infarction. Pericarditis, on the other hand, is frequent after irradiation of the mediastinum or of the left breast area.
The effects of different types of chemotherapy drugs are relatively well-known. Classic drugs, such as anthracyclines, cause irreversible myocardial damage as it is linked to direct damage to heart cells (cardiomyocytes). New anticancer drugs can cause high blood pressure, arrhythmias, left ventricular dysfunction and heart failure, but their effect appears to be reversible and less potent. The effect also depends on the total drug dose per body surface area and on the combination of different drugs, such as cyclophosphamide, trastuzumab and taxanes, female gender, pre-existing heart disease and high blood pressure, and / or courses of radiotherapy involving portions of the heart.
For example, for the anthracycline class of drugs (e.g. Doxorubicin and Epirubicin), the maximum cumulative toxic dose of doxorubicin is between 400-550 mg / m2. In some patients, ventricular dysfunction, which is usually asymptomatic, may however, even begin at lower doses, about 200 mg / m2.
For trastuzumab, on the other hand, about XNUMX/XNUMX of treated patients may develop Dilated Cardiomyopathy (DCM). But its cardiotoxicity is not dose-dependent and is often reversible upon cessation of therapy. About XNUMX% of patients develop DCM when trastuzumab is given alone, but this percentage rises to XNUMX% when combined with anthracycline and cyclophosphamide.
Prevention of damage seems possible with the administration of some drugs.
Treatment of breast cancer and Hodgkin's lymphoma with radiotherapy involves irradiation of portions of the heart and may cause short-term reactions (usually pericarditis even with abundant pericardial effusion), but especially after many years.
The long-term consequences, usually between 10 and 20 years later, sometimes even after 30 years, involve the coronary arteries, with manifestations of angina and myocardial infarction, left ventricle wall thinning and left ventricular dysfunction, valve damage, atrio-ventricular blocks, fibrosis of the pericardium which becomes less elastic and / or chronic pericardial effusion.
Currently, radiotherapy techniques can reduce the doses of radiation delivered and appear to be safer and more effective but it is not proven whether they have reduced long-term complications.