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Anthracycline therapy is included in many chemotherapy regimens and is known to be highly effective. However, it has a very important side effect such as cardiotoxicity. Anthracyclines can cause irreversible damage to heart cells, ultimately leading to heart failure; This condition may occur in the acute phase or years after treatment.

The aim of the PROACT study is to demonstrate the effectiveness of the ACE inhibitor enalapril in preventing cardiotoxicity in breast cancer and non-Hodgkin lymphoma (NHL) patients receiving anthracycline-based chemotherapy.

In this prospective, randomized and open-label study, patients diagnosed with breast cancer and NHL were randomized to enalapril or placebo to determine whether ACE inhibitors could help prevent anthracycline cardiotoxicity. Patients in the enalapril arm will begin treatment at least 2 days before starting chemotherapy and stop taking enalapril 3 weeks after the last anthracycline dose (starting with 2.5 mg twice daily and titrating to a maximum dose of 10 mg twice daily). All patients were planned to receive six cycles of anthracycline chemotherapy (?300 mg/m2 doxorubicin equivalent).

The primary endpoint of the study was the presence or absence of cardiac troponin T and troponin I release at any time during anthracycline therapy and 1 month after the last anthracycline dose. Secondary endpoints were determined as cardiac functions measured by echocardiographic evaluation, compliance with enalapril and side effects.

In the PROACT study, 111 patients (mean age 57 years, 78% women) treated for breast cancer (62%) or Non-Hodgkin's lymphoma (38%) in 13 centers in England were included in the study. 56 patients were included in the enalapril group and 55 patients were included in the placebo group. Cardiac troponin values were negative in all patients at the beginning of the study. During cancer treatment, patients were given anthracycline therapy at a dose equivalent to an average of 328 mg/m2 doxorubicin. The average dose of enalapril received by patients in the enalapril arm was 17.7 mg.

Considering the results of the PROACT study, troponin T release and an increase in troponin T values occurred in 77.8% of the patient group receiving enalapril treatment and 83.3% of the placebo group. Thus, no statistically significant difference was detected in the primary end point between these 2 groups (OR: 0.65, 95% CI: 0.23-1.78, p=0.405). Additionally, no significant difference was detected between the groups in terms of troponin I values (OR: 1.10, 95% CI: 0.50-2.38, p=0.819). When the echocardiographic evaluation results, which were determined as the secondary endpoint, were examined, the results in left ventricular global longitudinal strain (p=0.921) and ejection fraction (0.236) were found to be similar in both groups.

As a result, it was shown that enalapril, given to protect against cardiotoxicity, had no effect on cardiotoxicity and myocardial damage in patients receiving high-dose anthracycline chemotherapy.

According to the results of the PROACT study, patients treated for cancer with high-dose anthracycline chemotherapy and treated with enalapril as an ACE inhibitor showed no difference in troponin T levels one month after the last chemotherapy dose compared with those who did not receive it. However, the proportion of patients who tested positive for troponin I (47% of the enalapril group and 45% of the standard care group) was significantly lower in both groups compared with the proportion of patients who tested positive for troponin T, the researchers noted.

In the results of this study, it is necessary to draw attention to the findings about troponin I. Although both troponin values have been shown to be associated with cardiotoxicity in observational studies, the results of this study raise a question regarding which type of troponin we should use. Furthermore, it has been observed that ACE inhibitors are not a promising weapon for the future in preventing cardiotoxicity associated with anthracyclines.