Prevention of cancer therapy related cardiotoxicity

: A Tayside Pharmaco-Epidemiology study (PROTECT-TAYSIDE study)

Abstract

Cancer is the second highest cause of death in the world after cardiovascular disease. Despite the success of chemotherapeutic agents many patients are left with the unfortunate side effects of these drugs. Cytotoxic antibiotics such as anthracyclines and the monoclonal antibody trastuzamab are both commonly used in breast cancer and may cause irreversible cardiotoxicity, though trastuzumab-induced damage can be reversed upon stopping. Various animal studies have shown that cardioprotective drugs such as ACE inhibitors, Beta-blockers and statins can reduce pathological processes such as oxidative stress as a result of chemotherapy, however their protective role in human is currently unknown.

In this study, 1229 eligible breast cancer patients who received anthracyclines and/or trastuzumab as well as the use of cardioprotective agents were retrospectively observed to see if they have therapeutical effects in reversing myocardial damage. Furthermore, a population-based record-linkage study of all breast cancer patients in Tayside, Scotland undergoing adjuvant chemotherapy was carried out to audit the incidence of cardiotoxicity in breast cancer as well as adherence to guidelines which was never been evaluated previously. Results revealed that although the majority of patients had a baseline assessment, when they were divided into anthracycline + trastuzumab or anthracycline those receiving anthracycline only had suboptimal surveillance of cardiac function. Additionally, the latter group was observed to have a higher incidence of Left ventricular systolic dysfunction (LVSD) which is thought to be due to a lower rate of surveillance.

The hypothesis of this study was that the use of cardioprotective drugs such as ACE inhibitors, Beta blockers and ARBs as well as cholesterol controlling drugs such as statins may be able to reverse the cardiac damage caused by cancer therapy drugs such as anthracyclines how ever, the results from the overall PROTECT-TAYSIDE study were in disagreement with the hypothesis and showed that the use of cardioprotective drugs did not reverse anthracycline-induced cardiac damage.

Date of Award	2018
Original language	English
Awarding Institution	University of Dundee
Supervisor	Chim Lang (Supervisor), Allan Struthers (Supervisor) & Michelle Ferguson (Supervisor)