Randomized study of doxorubicin-based chemotherapy regimens, with and without sildenafil, with analysis of intermediate cardiac markers (original) (raw)
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Cardiology Research and Practice, 2022
Background. Previous animal studies have shown a protective effect of 5-phosphodiesterase inhibitors on cancer therapeutics-related cardiac dysfunction (CTRCD) of anthracyclines. Aim. The aim of this study was to evaluate the clinical effect of sildenafil on the primary prevention of CTRCD in human. Materials and Methods. In this randomized double-blind clinical trial, the primary end point was efficacy in preventing the reduction of left ventricular ejection fraction (LVEF). The intervention group patients received sildenafil at a dose of 25 milligrams twice a day before starting the chemotherapeutic regimen, and the control group received placebo. All the patients at baseline and after the 6-month follow-up underwent 4D and speckle-tracking echocardiography and cardiac MRI, accompanied by hs-troponin I and NT-Pro-BNP measurement. Results. Sixty patients were enrolled in this study, and data from 52 patients (24 patients in the intervention group and 28 patients in the control grou...
Circulation, 2005
Background— Sildenafil, a phosphodiesterase-5 inhibitor, induces cardioprotection against ischemia/reperfusion injury via opening of mitochondrial K ATP channels. It is unclear whether sildenafil would provide similar protection from doxorubicin-induced cardiotoxicity. Methods and Results— Male ICR mice were randomized to 1 of 4 treatments: saline, sildenafil, doxorubicin (5 mg/kg IP), and sildenafil (0.7 mg/kg IP) plus doxorubicin (n=6 per group). Apoptosis was assessed with the use of terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling and in situ oligo ligation methods. Desmin distribution was determined via immunofluorescence. Bcl-2 expression was analyzed by Western blot. Left ventricular function was assessed by measuring developed pressure and rate pressure product in Langendorff mode. ECG changes indicative of doxorubicin cardiotoxicity were also measured. For in vitro studies, adult ventricular cardiomyocytes were exposed to doxorubicin (1 μmol/L), sildena...
Proceedings of the National Academy of Sciences, 2010
We have shown that the potent phosphodiesterase-5 (PDE-5) inhibitor sildenafil (Viagra) induces a powerful effect on reduction of infarct size following ischemia/reperfusion injury and improvement of left ventricular dysfunction in the failing heart after myocardial infarction or doxorubicin (DOX) treatment. In the present study, we further investigated the potential effects of sildenafil on improving antitumor efficacy of DOX in prostate cancer. Cotreatment with sildenafil enhanced DOX-induced apoptosis in PC-3 and DU145 prostate cancer cells, which was mediated by enhanced generation of reactive oxygen species, up-regulation of caspase-3 and caspase-9 activities, reduced expression of Bcl-xL, and phosphorylation of Bad. Overexpression of Bcl-xL or dominant negative caspase 9 attenuated the synergistic effect of sildenafil and DOX on prostate cancer cell killing. Furthermore, treatment with sildenafil and DOX in mice bearing prostate tumor xenografts resulted in significant inhibition of tumor growth. The reduced tumor size was associated with amplified apoptotic cell death and increased expression of activated caspase 3. Doppler echocardiography showed that sildenafil treatment ameliorated DOX-induced left ventricular dysfunction. In conclusion, these results provide provocative evidence that sildenafil is both a powerful sensitizer of DOX-induced killing of prostate cancer while providing concurrent cardioprotective benefit. apoptosis | phosphodiesterase-5 | reactive oxygen species
Cardiac Complications of Chemotherapy: Role of Prevention
Current Treatment Options in Cardiovascular Medicine, 2014
Abbreviations CT chemotherapy I LVEF left ventricular ejection fraction I MUGA radionuclide multi-gated acquisition I NP natriuretic peptides I cTnI cardiac troponin I I cTnT cardiac troponin T I HF heart failure I AC anthracycline I LVD left ventricular dysfunction I HS highly sensitive I NT-proBNP N-terminal pro-brain natriuretic peptide I CMP cardiomyopathy I ACEI angiotensin-converting enzyme inhibitor I BB beta-blocker
STUDY THE EFFECT OF CHEMOTHERAPY ON THE CARDIAC FUNCTION
Advances in cancer therapy have resulted in significant improvement in long-term survival for many types of cancer but have also resulted in untoward side effects associated with treatment. One such complication that has become increasingly recognized is the development of cardiomyopathy and heart failure. The anthracyclines are arguably one of the most active groups of chemotherapy agents in oncology. Echocardiography has been employed to measure left ventricular ejection fraction as chemotherapy progresses, and once decreases in function are identified, chemotherapy dosage or frequency is modified, or the chemotherapy is stopped. Purpose: To detect the side effects of the chemotherapeutic agents on the cardiac function and to estimate the incidence and the features of subclinical cardiotoxicity induced after conventional treatment with doxorubicin-based chemotherapy for lymphoma and breast cancer patients Patients and Methods: This observational non controlled cross sectional study conducted in order to identify the clinical and Echo-Doppler signs of cardiovascular affection induced by Anthracyclines–based chemotherapy in female patients with breast cancer and lymphoma. Echocardiograms were performed before and 6 cycles after intiation of therapy with anthracyclines,. Clinical cardiomyopathy was defined by the presence of clinical signs of congestive heart failure (CHF) and decrease of left ventricular ejection fraction (EF). Cumulative dose of doxorubicin, diabetes, dyslipidemia, older age were evaluated as potential risk factors for the development of cardiac dysfunction. Results: Cardiotoxic side effects developed in about one fourth of cancer breast patients and also lymphoma patients after Doxorubicin therapy .These toxicity were in the form of dilated cardiomyopathy (8.7%) in breast cancer patients and (8%) in lymphoma patients , pulmonary hypertension (7.3%) in breast cancer patients and (4%) in lymphoma patients, diastolic dysfunction (10%) in breast cancer patients and ( 12% ) in lymphoma ,mitral regurgitation (12%)in breast cancer patients and (8%) in lymphoma patients and abnormal ECG changes ( 13 % ). The most evident risk factors for the development of cardiotoxicity is the cumulative dose, advanced age, Diabetes Mellitus, Dyslipidemia and hypertension.anthracycline induced cardiomyopthy is related to number of received cycles of doxurubicin .A change in the left ventricular dimensions and functions ( systolic and diastolic) as determined by echocardiography, may be an indicator of developing cardiotoxicity Conclusion: chemotherapy induced cardiomyopathy is a serious complication of cancer therapy rendering the timely identification of high-risk patients the key to reducing this risk. A unified acceptable definition of chemotherapy induced cardiomyopathy adopted by cardiologists and oncologists must be developed.
Cardiac Toxicity of Anticancer Agents
Current Cardiology Reports, 2013
Modern cancer therapies are highly effective in the treatment of various malignancies, but their use is limited by the potential for cardiotoxicity. The most frequent and typical clinical manifestation of cardiotoxicity is left ventricular dysfunction, induced not only by cytotoxic conventional cancer therapy like anthracyclines, but also by new antitumor targeted therapy such as trastuzumab. The current standard for monitoring cardiac function, based on periodic assessment of left ventricular ejection fraction detects cardiotoxicity only when a functional impairment has already occurred, precluding any chance of preventing its development. A novel approach, based on the use of cardiac biomarkers has emerged in the last decade, resulting in a cost-effective diagnostic tool for early, real-time identification, assessment and monitoring of cardiotoxicity. In particular, prophylactic treatment with enalapril in patients with an early increase in troponin after chemotherapy has been shown to be very effective in preventing left ventricular dysfunction and associated cardiac events. In patients developing cancer treatment induced-cardiomyopathy, complete left ventricular ejection fraction recovery and a reduction of cardiac events may be achieved only when left ventricular dysfunction is detected early after the end of cancer treatment and treatment with angiotensin-converting enzyme inhibitors, possibly in combination with beta-blockers, is promptly initiated.
Indian Heart Journal, 2018
Objective: Deterioration in ventricular function is often observed in patients treated with anthracyclines for cancer. There is a paucity of evidence on interventions that might provide cardio-protection. We investigated whether prophylactic use of carvedilol can prevent doxorubicin-induced cardiotoxicity and whether any observed effect is dose related. Methods: A prospective, randomized, double-blind study in patients treated with doxorubicin, comparing placebo (n = 38) with different doses of carvedilol [6.25 mg/day (n = 41), 12.5 mg/day (n = 38) or 25 mg/ day (n = 37)]. The primary endpoint was the measured change in left ventricular ejection fraction (LVEF) from baseline to 6 months. Results: LVEF decreased from 62 AE 5% at baseline to 58 AE 7% at 6-months (p = 0.002) in patients assigned to placebo but no statistically significant changes were observed in any of the 3 carvedilol groups. At 6 months, only one of 116 patients (1%) assigned to carvedilol had an LVEF < 50% compared to four of the 38 assigned to placebo (11%), (p = 0.013). No significant differences were noted between carvedilol and placebo in terms of the development of diastolic dysfunction, clinically overt heart failure or death. Conclusions: Carvedilol might prevent deterioration in LVEF in cancer patients treated with doxorubicin. This effect may not be dose related within the studied range.
Doxorubicin-induced cardiotoxicity in adult Indian patients on chemotherapy
Indian Journal of Medical and Paediatric Oncology, 2009
Background:Doxorubicin-induced cardiotoxicity is widely known to occur at cumulative doses exceeding 450 mg/m2 . However, very few studies have reported incidence of cardiac dysfunction in patients on chemotherapy with lower cumulative doses. To the best of our knowledge, there is no study carried out so far that has reported the incidence of cardiac dysfunction in adult Indian patients receiving doxorubicin. This study was undertaken to determine the incidence of doxorubicin-induced cardiotoxicity by serial resting echocardiography in patients on chemotherapy and identify risk factors associated with cardiotoxicity.Materials and Methods:Patients that were started on doxorubicin-based chemotherapy in the period from January 2000 to June 2001 and had completed at least 300 mg/m2cumulative dose were taken in the study. Electrocardiography, chest X-ray and echocardiography were done at baseline, at 300 mg/m2and at 450 mg/m2cumulative doses of doxorubicin. All patients were evaluated fo...