Cardiovascular events after polychemotherapy of oncohematological diseases: modern ways to prevention and treatment

Abstract

Heart dysfunction that occurred after using of cytostatic drugs and monoclonal antibodies may be a limit factor in treatment of oncohematological diseases. Side effects of chemotherapy include decline of quality of life, hypotension, hypertension, arrhythmias, conduction disturbances, pericarditis, thromboembolic events, heart failure, death. The risk of cardiotoxicity may be increased by some factors that include drug exposure, age, history of cardiovascular diseases, drug combination, previous radiotherapy or chemotherapy.

Because of improvements in therapy of oncohematological diseases, cardiovascular and cerebrovascular complications rose to become the leading causes of death. Patients with oncohematological diseases who undergoes chemotherapy or chemoprevention are at a substantial risk for the deterioration of their cardiovascular health. In the past, this risk was less evident because the life span of a patient with oncohematological disease was often too short to make the cardiovascular complications a major matter of concern.

Several drugs may be added to chemotherapy to reduce cardiotoxicity without losing of the antitumor activity, and possibly even to enhance antitumor activity. Most of these approaches are still experimental. However, some could easily be considered for clinical trials.

Dexrazoxane iron chelates prevents the generation of cardiotoxic reactive oxygen species, is a drug used to protect the myocardium from anthracycline-induced cardiotoxicity. However, this drug may increase the risk of adverse effects, such as a slightly higher incidence of myelosuppression, infection, and fever.

Lipid-lowering agents have been indicated as protective agents against chemotherapy-mediated cardiotoxicity. Statins seem to have a chemopreventive and direct antitumor effect. Whether statins may have protective or harmful effects on cancer risk is still a matter of debate, but the most recent reviews of the literature suggest that these drugs do not have short-term negative consequences on cancer risk. Moreover, they can have an antithrombotic effect that could lower the risk of thrombosis induced by chemotherapy.

In spite of theoretical expectations and encouraging results obtained in experimental models, all randomized controlled trials in which potential cardioprotective agents (coenzyme Q10, l -carnitine, carvedilol, combinations of vitamins E and C) were tested in oncological and oncohematological patients had methodological limitations.

Because of that fact that damage in the endothelium appears to be the underlying mechanism for the cardiotoxicity of a variety of chemotherapeutic drugs, agents that prevent endothelial cell apoptosis should provide protective effects. Investigation of some antiangiogenic compounds have also been found to render endothelial cells more resistant to apoptosis induced by external stimuli. The concept is that these agents force the endothelial cell into a quiescent state that leads to increased resistance to apoptosis.

Because the pathogenesis of both cardiovascular disease and cancer is frequently linked to inflammation, it follows that prevention of inflammation should protect from both diseases.

CONCLUSIONS: Close monitoring of patients is essential to decrease the risk of chemotherapy-induced cardiotoxicity and is in the early implementation of cardioprotective therapies. Development of cardioprotection during and after chemotherapy is another area that needs to be focused on the translation of the laboratory discoveries into clinical trials and on the development of the consensus protocols.

Key words: cardiovascular events, chemotherapy, prevention, treatment.