enalapril and Lymphoma

Anthracyclines are included in chemotherapy regimens to treat several different types of cancer and are extremely effective. However, it is recognised that a significant side effect is cardiotoxicity; anthracyclines can cause irreversible damage to cardiac cells and ultimately impaired cardiac function and heart failure, which may only be evident years after exposure. The PROACT trial will establish the effectiveness of the ACE inhibitor enalapril maleate (enalapril) in preventing cardiotoxicity in patients with breast cancer and non-Hodgkin's lymphoma (NHL) receiving anthracycline-based chemotherapy.. PROACT is a prospective, randomised, open-label, blinded end-point, superiority trial which will recruit adult patients being treated for breast cancer and NHL at NHS hospitals throughout England. The trial aims to recruit 106 participants, who will be randomised to standard care (high-dose anthracycline-based chemotherapy) plus enalapril (intervention) or standard care alone (control). Patients randomised to the intervention arm will receive enalapril (starting at 2.5 mg two times per day and titrating up to a maximum dose of 10 mg two times per day), commencing treatment at least 2 days prior to starting chemotherapy and finishing 3 weeks after their last anthracycline dose. The primary outcome is the presence or absence of cardiac troponin T release at any time during anthracycline treatment, and 1 month after the last dose of anthracycline. Secondary outcomes will focus on cardiac function measured using echocardiogram assessment, adherence to enalapril and side effects.. A favourable opinion was given following research ethics committee review by West Midlands-Edgbaston REC, Ref: 17/WM/0248. Trial findings will be disseminated through engagement with patients, the oncology and cardiology communities, NHS management and commissioning groups and through peer-reviewed publication.. NCT03265574.

Topics: Adult; Anthracyclines; Antibiotics, Antineoplastic; Breast Neoplasms; Cardiotoxicity; Enalapril; Female; Humans; Lymphoma; Lymphoma, Non-Hodgkin; Multicenter Studies as Topic; Prospective Studies; Randomized Controlled Trials as Topic

Anthracyclines, such as doxorubicin, though widely used in anticancer therapy, they are associated with cardiotoxic side-effects. The aim of this trial was to investigate long-term follow-up cardiotoxicity findings in patients treated with doxorubicin and concomitant metoprolol or enalapril 10 years earlier.. Overall, 147 patients were randomized into the treatment arms. A total of 125 patients treated with doxorubicin without evidence of heart disease at the start of chemotherapy were analyzed. They were followed-up for up to 10 years after treatment start.. A total of 47 patients completed the follow-up and 21 patients died, none due to cardiotoxicity events. Clinical signs of heart failure were not seen in any patients and no statistically significant differences between baseline and 10-year findings were seen for echocardiographic variables. No evidence of long-term cardiotoxicity was seen and nor metoprolol or enalapril offered an additional benefit.

Topics: Adolescent; Anthracyclines; Antibiotics, Antineoplastic; Cardiotoxicity; Doxorubicin; Echocardiography; Enalapril; Female; Heart Failure; Humans; Lymphoma; Male; Metoprolol; Prospective Studies

Several measures including drugs have been tried to reduce anthracycline cardiotoxicity. The lack of randomized trials prompted this study to assess the role of an angiotensin converting enzyme (ACE) inhibitor (enalapril) in anthracycline-induced cardiotoxicity in children with hematological malignancies.. A randomized, double-blind, placebo-controlled trial was conducted on 84 patients with leukemia (41) and lymphoma (43) who received anthracyclines (doxorubicin and/or daunorubicin) at cumulative dose ≥200 mg/m. LVEF decreased in both groups at 6 months, more so in group B (62.25 ± 5.49 vs 56.15 ± 4.79, P < 0.001). A ≥20% decrease was seen in 3 patients in group B but none in group A (P = 0.21). Cardiac biomarkers increased more in group B at 6 months, and the increase was significant for proBNP (49.60 ± 35.97 vs 98.60 ± 54.24, P < 0.001) and cTnI (0.01 ± 0.00 vs 0.011 ± 0.003, P = 0.035) but not significant for CK-MB (1.08 ± 0.18 vs 1.21 ± 0.44, P = 0.079). In group A, 9.1% of the patients showed an increase in proBNP level ≥100 compared with 37.5% in group B (P < 0.001). No patient developed heart failure or arrhythmia.. Enalapril has a role in reducing cardiac toxicity after anthracycline administration.

Topics: Angiotensin-Converting Enzyme Inhibitors; Anthracyclines; Antibiotics, Antineoplastic; Cardiotoxicity; Child; Daunorubicin; Double-Blind Method; Doxorubicin; Enalapril; Female; Heart Failure; Humans; Lymphoma; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Anthracyclines have contributed to a marked increase in survival in different types of cancer [1,2]. Unfortunately, they are associated with dose-dependent cardiotoxicity and heart failure (HF) [3–8]. Change to a weekly dosage schedule with slow infusions has been tested, a strategy that requires more frequent hospital visits and increased storage resources[7,9]. Liposomal anthracycline formulations with reduced drug exposure and lower plasma concentrations may still be cardiotoxic at higher cumulative doses [10]. Beta-blockers and angiotensin converting enzyme(ACE) inhibitors have been shown to reduce anthracycline-induced cardiotoxicity,but have not been tested in long-term prospective, randomized,controlled studies with well defined cardiotoxicity criteria and careful cardiac function monitoring [11–16]. We investigated doxorubicin-induced clinical or subclinical cardiotoxicity in lymphoma patients after concomitant prophylactic therapy with metoprolol or enalapril or no concomitant treatment. We examined whether cardiotoxicity was related to the treatment or any other variable. We found that HF was less frequent under concomitant treatment than no treatment, especially in the metoprolol group, but the differences were not significant. No association was found between the presence of cardiotoxicity and concomitant treatment or other variable apart of age that had a significant impact. The marginal benefit seen with metoprolol should be investigated further.

Topics: Adrenergic beta-1 Receptor Antagonists; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antibiotics, Antineoplastic; Cardiotonic Agents; Chemoprevention; Doxorubicin; Enalapril; Female; Heart Diseases; Humans; Lymphoma; Male; Metoprolol; Middle Aged; Premedication