Therefore, the current study aimed to assess if enx could. However, their clinical utility is tempered by a dosedependent risk of cardiotoxicity and congestive heart failure. The mechanisms accounting for anthracyclineinduced cardiac damage are complex and interrelated. Yi x1, bekeredjian r, defilippis nj, siddiquee z, fernandez e, shohet rv. Several mechanisms have been associated with the pathogenesis of anthracycline induced heart disease, including oxidative stress, ion dysregulation and modifications of cardiac gene expression. Acute anthracyclineinduced cardiotoxicity occurs in less than 1% of childhood cancer patients and is defined as an acute, but transient, decrease in. Other suggested mechanisms include decreased number of contractile cells as a result of damage to mitochondrial and cellular membranes, and extracellular matrix remodelling. T1 prevention and management of cardiotoxicity from antineoplastic therapy. Prevention of anthracyclineinduced cardiotoxicity jacc. Midwestern university college of pharmacy glendale goal. Type i vs type ii cardiotoxicity type i cardiotoxicity eg anthracycline type ii cardiotoxicity eg trastuzumab clinical course, response to medication may stabilise, but subclinical damage seems to persist.
Cardioprotective potential of buchanania axillaris on doxorubicin induced cardiotoxicity in albino rats. Doxorubicininduced cardiomyopathy 17 years after chemotherapy. Clinical hf may ensue in up to 5% of highrisk patients. Pdf on nov 14, 2018, danubia silva dos santos and others published doxorubicininduced cardiotoxicity. Actually, the timing of anthracycline induced cardiotoxicity is not well defined, because, at present, no prospective study has regularly monitored cardiac function in adult patients for 3 years. The mechanism of doxs cardiotoxicity is complex and may involve oxidative 2,3, nitrosative and nitrative. N2 cardiotoxicity is a major side effect of various antineoplastic agents, particularly the anthracyclines. Prevention of anthracycline induced cardiotoxicity challenges and opportunities pimprapa vejpongsa, md, edward t.
Cardiac complications were first reported a few years after the introduction of daunorubicin. Cardiotoxicity of anthracycline agents for the treatment of. Earlyonset cardiomyopathy induced by doxorubicin dox occurs during the year after the completion of chemotherapy. Cancer treatmentrelated cardiotoxicity includes efforts to identify individual toxicity risks and prevention strategies support the national cancer insitutes goal of reducing the burden of cancer diagnoses and treatment outcomes. The complex and not completely understood pathogenesis of this complication makes difficult to design successful preventive or curative measures. Early detection of anthracycline cardiotoxicity and. The anticancer drug doxorubicin dox also referred to as adriamycin is highly effective in the treatment of a broad range of cancers. Beyond its anticoagulant action, enoxaparin enx, a low molecular weight heparin, has been shown to exert multiple pharmacological actions including antioxidant, antiinflammatory and antiapoptotic effects. The mortality rate from overdose remains significantly more up to 10% than other antidepressants. The goal of this article is to educate pharmacists of the impact. Cancer treatmentrelated cardiotoxicity egrpdccpsncinih. In keeping with this view, feeding of rats with ironrich food exacerbates weight loss and myocyte injury induced by doxorubicin. Anthracyclineinduced doxorubicin, daunorubicin, epirubicin, idarubicin cardiomyopathy is a disease spectrum ranging from development of heart failure hf with symptoms and clinical signs to asymptomatic decline in left ventricular ejection fraction lvef. Treatment with doxorubicin dox, which is an effective anticancer agent, is limited by cardiotoxicity.
Lateonset dox induced cardiomyopathy, which occurs later than a year after chemotherapy has been completed, has been reported chiefly in pediatric populations. Doxorubicin is a highly efficacious anticancer drug but causes cardiotoxicity in many patients. Anthracyclines are commonly used antineoplastic drugs. Jan 10, 2018 doxorubicin dox is commonly used in the treatment of many types of cancers but its cardiotoxicity is limiting its clinical use. Studies in cells and animals suggest that the mechanism of anthracycline induced cardiotoxicity aic is multifactorial. Oct 23, 20 prevention of anthracycline induced cardiotoxicity icosone the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Whereas cardiotoxicity defines any adverse alteration, including those with no proven consequence changes on biopsy, decreases of lvef, actionable cardiotoxicity defines symptomatic or asymptomatic findings of a higher level of concern that should prompt interventions. Risk factors for anthracycline induced cardiotoxicity.
Reference lists of retrieved articles were also scanned for additional articles. Anthracycline therapy is associated with an increase in the risk for developing heart failure with significant associated morbidity and mortality 1. In 1979, a dosetoxicity curve was generated by plotting the incidence of heart failure defined by clinical signs and symptoms such as shortness of breath, neck vein distension, s3 gallop, cardiomegaly, hepatomegaly, or. Sep 15, 2010 anthracyclines are common chemotherapeutic agents used to treat many different types of cancer. Nineyearold girl with stage iv hodgkin lymphoma with 12 epirubicin doses and a cumulative dose of 576 mgm 2. Doxinduced cardiac oxidative stress, toxicity, and dysfunction. Studies in cells and animals suggest that the mechanism of anthracyclineinduced cardiotoxicity aic is. Regimens using newer combinations of agents, the most widely studied of which is the monoclonal antibody trastuzumab, are known to augment the cardiotoxicity of anthracyclines. The prevention, detection and management of cancer. Overview of studies examining the roles of oxidative stress and free cellular iron tomassimunek1, martin stirba2, olga popelova2, michaela adamcova2, radomir hrdina1, vladimir gersl2 1charles university in prague, faculty of pharmacy in hradec kralove, heyrovskeho 1203, 500 05. Nebivolol prevents anthracycline induced cardiotoxicity, according to research presented at esc congress 2016 today by professor mirela cleopatra tomescu, a cardiologist at victor babes university. Considering oxidative stress to be the primary cause of doxinduced cardiomyopathy 3, 4, we first determined myocardial oxidative stress and cell death in the acute model of doxinduced cardiotoxicity which has been characterized as a rapid cardiomyocyte necrosis and reduced cardiac output within 4. Enoxaparin attenuates doxorubicin induced cardiotoxicity.
More than 70 percent of children who are treated for childhood cancer can be cured. Although redox induced damage is likely involved in anthracycline induced cardiotoxicity, some evidence suggests that it is not the only mechanism at play. The mechanisms of doxorubicin induced cardiotoxicity dic remain incompletely understood. Although redoxinduced damage is likely involved in anthracyclineinduced cardiotoxicity, some evidence suggests that it is not the only mechanism at play. A serious side effect of some common cancer treatments is cardiotoxicity. It was first recognised to be related to the oxidative stress induced by anthracyclines. Dec 21, 2017 anthracycline induced doxorubicin, daunorubicin, epirubicin, idarubicin cardiomyopathy is a disease spectrum ranging from development of heart failure hf with symptoms and clinical signs to asymptomatic decline in left ventricular ejection fraction lvef. Nebivolol prevents anthracyclineinduced cardiotoxicity, according to research presented at esc congress 2016 today by professor mirela cleopatra tomescu, a cardiologist at victor babes university. The prevention, detection and management of cancer treatment. The benefits associated with some cancer treatments do not come without risk. The mechanisms of doxorubicininduced cardiotoxicity dic remain incompletely understood. To further assess whether reduced sgc activity plays a pathogenic role in doxorubicin induced cardiotoxicity, we studied a mouse model in which decreased cardiac sgc activity was induced by.
The cause of dox induced cardiotoxicity is multifactorial and includes free radical induced. Anthracyclinedependent oxidative stress has long been associated to the ability of these drugs to chelate free iron, thereby forming irondoxorubicin complexes which, in turn, react with oxygen and trigger ros production. Monitoring parameters, prevention, and future chemotherapy by sarah nguyen, pharm. Doxorubicininduced cardiotoxicity is mediated by top2. Dingell veterans association medical center, detroit, michigan, usa correspondence. Lecuyer2 1department of pathology, 2department of pediatrics, wayne state university medical school, detroit, and 3john d. Anthracyclineinduced cardiotoxicity and the cardiac. Preventing the cardiotoxic effects of anthracyclines. Cardioprotective potential of buchanania axillaris on. This editorial refers to diverging effects of enalapril or eplerenone in primary prevention against doxorubicininduced cardiotoxicity by r. Mechanisms and management of doxorubicin cardiotoxicity. The mechanisms accounting for anthracycline induced cardiac damage are complex and interrelated.
From mechanisms to development of efficient therapy find, read and cite all the research. Risk factors for anthracyclineinduced cardiotoxicity. Despite almost 50 years of research, anthracycline cardiotoxicity remains a paramount challenge in terms of involved processes and prevention. Although cardiomyocyte has been considered a classical cellular target, other cells including various types of. Kanagavalli 1 1department of biochemistry, adiparasakthi college of arts and science, kalavai632 506, vellore district. Listing a study does not mean it has been evaluated by the u. Yeh, mdy abstract anthracycline compounds are major culprits in chemotherapy induced cardiotoxicity, which is the chief limiting factor in delivering optimal chemotherapy to cancer patients. Considering oxidative stress to be the primary cause of dox induced cardiomyopathy 3, 4, we first determined myocardial oxidative stress and cell death in the acute model of dox induced cardiotoxicity which has been characterized as a rapid cardiomyocyte necrosis and reduced cardiac output within 4 days after a single. Modeling doxorubicininduced cardiotoxicity in human.
Protection from doxorubicininduced cardiac toxicity in. Cardiotoxicity in childhood cancer survivors medscape. Analysis of the clinicopathological aspects of documented acute anthracyclineinduced cardiotoxicity in patients treated for acute leukaemia at the university hospital of zurich, switzerland, between 1990 and 1996. New signal transduction paradigms in anthracyclineinduced. Swamy 2 delhi institute of pharmaceutical sciences and research dipsar, pusph vihar, new delhi, india 1. In 1979, a dosetoxicity curve was generated by plotting the incidence of heart failure defined by clinical signs and symptoms such as shortness of breath, neck vein distension, s3 gallop, cardiomegaly, hepatomegaly, or pericardial effusion. Here we show that cardiomyocytespecific deletion of top2b encoding topoisomeraseii. Identification of the molecular basis of doxorubicininduced. Mechanisms of anthracycline cardiotoxicity and strategies to. Anthracyclines are common chemotherapeutic agents used to treat many different types of cancer.
Prevention of anthracyclineinduced cardiotoxicity full. In addition to its principal toxic mechanisms involving iron and redox reactions, recent studies have described new mechanisms of doxorubicin induced cell death, including abnormal protein processing, hyperactivated innate immune responses, inhibition of neuregulin1 nrg1erbbher. Dec 19, 2017 this editorial refers to diverging effects of enalapril or eplerenone in primary prevention against doxorubicininduced cardiotoxicity by r. Doxorubicin cardiotoxicity can be acute, occurring during and within 23 days of its administration. Doxorubicin is believed to cause dosedependent cardiotoxicity through redox cycling and the generation of reactive oxygen species ros.
Strain imaging and anthracycline cardiotoxicity the british. Cardiotoxicity of anthracycline agents for the treatment. Molecular basis of anthracyclineinduced cardiotoxicity richard s. Erbb2erbb4 and nrg1 signalling anthracyclines may also disrupt neuregulinerbb nrg receptor signalling to downstream cardiomyocyte prosurvival cascades involving the serinethreonine protein kinase b. Understanding the current state of knowledge and developing future research priorities, a 20 workshop sponsored by the epidemiology and genomics research program. Nebivolol prevents anthracyclineinduced cardiotoxicity, according to research presented at esc congress 2016 today by professor mirela cleopatra tomescu, a.
Doxorubicins cardiotoxicity is mainly due to oxidative stress, which is induced by the production of reactive oxygen species ros and mitochondrial damage. Acute anthracycline induced cardiotoxicity occurs in less than 1% of childhood cancer patients and is defined as an acute, but transient, decrease in lv. Transcriptional analysis of doxorubicin induced cardiotoxicity. In 2003, heart failure incidences of 5%, 16%, and 26% were estimated for cumulative doxorubicin doses of 400, 500, and 550 mgm2, respectively 6, resulting in a modi. The cardiotoxicity of doxorubicin is becoming an interdisciplinary point of interest given a growing population of cancer survivors. Nebivolol prevents anthracyclineinduced cardiotoxicity, according to research presented at esc congress 2016 today by professor mirela cleopatra tomescu, a cardiologist at victor babes university of medicine and pharmacy, timisoara, romania. For longterm survivors, possible late effects of treatment and their consequences for the quality of. Kles college of pharmacy klecop, vidyanagar, hubli, karnataka, india 2. Doxorubicin is associated with cardiotoxicity in 326 % of treated patients, trastuzumab in 228 % and sunitinib in 2. A redox perspective article pdf available in frontiers in physiology 9 march 2018 with 1,885 reads how we measure reads. However, anthracycline induced cardiotoxicity aic is a serious adverse drug reaction that affects the survival in patients treated for childhood cancer. A study of tca induced seizures has shown that seizures are generalized, brief, and occur within 1. Aug 28, 2016 nebivolol prevents anthracycline induced cardiotoxicity, according to research presented at esc congress 2016 today by professor mirela cleopatra tomescu, a cardiologist at victor babes university.
Enoxaparin attenuates doxorubicin induced cardiotoxicity in. Although cardiomyocyte has been considered a classical cellular target, other cells. The manifestations are usually chest pain due to myopericarditis andor palpitations due to sinus tachycardia, paroxysmal nonsustained supraventricular tachycardia and premature atrial and ventricular. Doxorubicin is an effective antitumor agent with a cumulative dosedependent cardiotoxicity. Nebivolol prevents anthracyclineinduced cardiotoxicity. Mechanisms of anthracycline cardiotoxicity and strategies. Dingell veterans association medical center, detroit, michigan, usa. Czuczman, md abstract cardiotoxicity is a major side effect of various antineoplastic agents, particularly the anthracyclines.
Identification of the molecular basis of doxorubicin. Anthracyclineinduced acute cardiotoxicity in adults treated for leukaemia. Dox induced cardiac oxidative stress, toxicity, and dysfunction. Jan 15, 2008 regimens using newer combinations of agents, the most widely studied of which is the monoclonal antibody trastuzumab, are known to augment the cardiotoxicity of anthracyclines. Doxorubicin dox is commonly used in the treatment of many types of cancers but its cardiotoxicity is limiting its clinical use. Anthracyclineinduced cardiotoxicity and the cardiacsparing. The incidence of acute cardiotoxicity is approximately 11% 3,4.
Unfortunately, the use of anthracyclines is limited by their cardiotoxic effects, which may become manifest as late as 20 years from initial exposure. Cardiotoxicity presents acutely during cancer treatment, potentially limiting dose and reducing the effectiveness of cancer treatment, and decades after treatment, leading to early mortality due to accelerated treatment induced heart disease. Actually, the timing of anthracyclineinduced cardiotoxicity is not well defined, because, at present, no prospective study has regularly monitored cardiac function in adult patients for 3 years. Anthracycline induced cardiotoxicity aic sawyer db. Transcriptional analysis of doxorubicininduced cardiotoxicity.
Current preventive measures focus on dose reduction, use of less cardiotoxic anthracycline analogues and prophylactic use of dexrazoxane. Doxorubicin dox is one of the most commonly used broadspectrum chemotherapeutic drugs. Prevention of anthracyclineinduced cardiotoxicity icosone the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Strategies to reduce the cardiotoxicity of anthracyclines figure 4 summarized the factors. Randomized controlled trials were sought using comprehensive searches of electronic databases in june 2008. The anthracyclines and related compounds doxorubicin, daunorubicin, idarubicin, epirubicin, and the anthraquinone mitoxantrone are among the chemotherapeutic agents implicated in cardiotoxicity.
530 1327 40 987 1076 705 943 64 1212 1223 1162 165 802 57 1564 618 485 854 1317 47 514 929 1475 642 1094 820 429 953 644 508 1156 971 810 847 1011 796 22 1468 896 343 451 997 492 1230 280