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Deutsches Arzteblatt International Mar 2014Cardiotoxic and other side effects limit the usefulness of treatments for cancer. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cardiotoxic and other side effects limit the usefulness of treatments for cancer.
METHOD
This article is based on pertinent articles that were retrieved by a selective search in PubMed and other databases, and on the guidelines of the European Society of Cardiology, the Association of Scientific Medical Societies in Germany, and the European Society of Medical Oncology.
RESULTS
Prospective studies have shown that some treatments for cancer are cardiotoxic. The heart damage that they cause can manifest itself as arrhythmia, arterial hypertension, thromboembolism, angina pectoris, myocardial infarction, or heart failure. It has been observed that potentially lethal complications can arise as late as 40 years after treatment of the original cancer. The anthracycline drug doxorubicin, given in a dose of 500 mg/m2 of body surface area, has been found to cause cardiac complications in 4-36% of the patients treated with it. Trastuzumab and epirubicin cause dose-limiting cardiac events in 1.7-5% of patients, depending on the dosage. Paclitaxel causes bradycardia, intracardiac conduction block, or arrhythmia in 0.5% of patients. 18% of patients treated with sunitimib or sorafenib have clinical manifestations relating to the heart (angina pectoris, dyspnea). 5-fluorouracil can cause angina pectoris at the beginning of treatment and rarely causes myocardial infarction. Cardiac radiation therapy, a form of treatment practiced in earlier decades, can cause cardiac complications 20 years after the event. The opportunity to prevent cardiac complications of anthracycline drugs with dexrazoxane is decidedly limited, but initial studies have shown that treatment with beta-blockers and ACE inhibitors lessens the likelihood of cardiotoxic side effects. When cardiac complications arise, the generally applicable rules for the treatment of each type of cardiac problem should be followed. The oncological treatment protocol should be adjusted or switched to one that is less damaging to the heart.
CONCLUSION
Treating physicians need to be thoroughly acquainted with the cardiotoxic effects of anti-cancer drugs so that they can diagnose them early on and avoid jeopardizing the overall success of treatment.
Topics: Antineoplastic Agents; Comorbidity; Evidence-Based Medicine; Heart Diseases; Humans; Incidence; Neoplasms; Risk Factors; Survival Rate
PubMed: 24666651
DOI: 10.3238/arztebl.2014.0161 -
Annual Review of Medicine 2015Treatment advances have increased survival in children with cancer, but subclinical, progressive, irreversible, and sometimes fatal treatment-related cardiovascular... (Review)
Review
Treatment advances have increased survival in children with cancer, but subclinical, progressive, irreversible, and sometimes fatal treatment-related cardiovascular effects may appear years later. Cardio-oncologists have identified promising preventive and treatment strategies. Dexrazoxane provides long-term cardioprotection from doxorubicin-associated cardiotoxicity without compromising the efficacy of anticancer treatment. Continuous infusion of doxorubicin is as effective as bolus administration in leukemia treatment, but no evidence has indicated that it provides long-term cardioprotection; continuous infusions should be eliminated from pediatric cancer treatment. Angiotensin-converting enzyme inhibitors can delay the progression of subclinical and clinical cardiotoxicity. All survivors, regardless of whether they were treated with anthracyclines or radiation, should be monitored for systemic inflammation and the risk of premature cardiovascular disease. Echocardiographic screening must be supplemented with screening for biomarkers of cardiotoxicity and perhaps by identification of genetic susceptibilities to cardiovascular diseases; optimal strategies need to be identified. The health burden related to cancer treatment will increase as this population expands and ages.
Topics: Adult; Antineoplastic Agents; Cardiotonic Agents; Cardiotoxicity; Cardiovascular Diseases; Child; Dexrazoxane; Doxorubicin; Humans; Neoplasms; Survivors
PubMed: 25587648
DOI: 10.1146/annurev-med-070213-054849 -
Cardio-oncology (London, England) 2019Cancer diagnostics and therapies have improved steadily over the last few decades, markedly increasing life expectancy for patients at all ages. However, conventional... (Review)
Review
Cancer diagnostics and therapies have improved steadily over the last few decades, markedly increasing life expectancy for patients at all ages. However, conventional and newer anti-neoplastic therapies can cause short- and long-term cardiotoxicity. The clinical implications of this cardiotoxicity become more important with the increasing use of cardiotoxic drugs. The implications are especially serious among patients predisposed to adverse cardiac effects, such as youth, the elderly, those with cardiovascular comorbidities, and those receiving additional chemotherapies or thoracic radiation. However, the optimal strategy for preventing and managing chemotherapy-induced cardiotoxicity remains unknown. The routine use of neurohormonal antagonists for cardioprotection is not currently justified, given the marginal benefits and associated adverse events, particularly with long-term use. The only United States Food and Drug Administration and European Medicines Agency approved treatment for preventing anthracycline-related cardiomyopathy is dexrazoxane. We advocate administering dexrazoxane during cancer treatment to limit the cardiotoxic effects of anthracycline chemotherapy.
PubMed: 32154024
DOI: 10.1186/s40959-019-0054-5 -
Pharmacological Research Sep 2022Iron participates in myriad processes necessary to sustain life. During the past decades, great efforts have been made to understand iron regulation and function in... (Review)
Review
Iron participates in myriad processes necessary to sustain life. During the past decades, great efforts have been made to understand iron regulation and function in health and disease. Indeed, iron is associated with both physiological (e.g., immune cell biology and function and hematopoiesis) and pathological (e.g., inflammatory and infectious diseases, ferroptosis and ferritinophagy) processes, yet few studies have addressed the potential functional link between iron, the aforementioned processes and extramedullary hematopoiesis, despite the obvious benefits that this could bring to clinical practice. Further investigation in this direction will shape the future development of individualized treatments for iron-linked diseases and chronic inflammatory disorders, including extramedullary hematopoiesis, metabolic syndrome, cardiovascular diseases and cancer.
Topics: Ferroptosis; Hematopoiesis, Extramedullary; Homeostasis; Humans; Iron; Iron Metabolism Disorders
PubMed: 35933006
DOI: 10.1016/j.phrs.2022.106386 -
Frontiers in Cardiovascular Medicine 2023Pediatric acute myeloid leukemia (AML) therapy is associated with substantial short- and long-term treatment-related cardiotoxicity mainly due to high-dose anthracycline...
BACKGROUND
Pediatric acute myeloid leukemia (AML) therapy is associated with substantial short- and long-term treatment-related cardiotoxicity mainly due to high-dose anthracycline exposure. Early left ventricular systolic dysfunction (LVSD) compromises anthracycline delivery and is associated with inferior event-free and overall survival in pediatric AML. Thus, effective cardioprotective strategies and cardiotoxicity risk predictors are critical to optimize cancer therapy delivery and enable early interventions to prevent progressive LVSD. While dexrazoxane-based cardioprotection reduces short-term cardiotoxicity without compromising cancer survival, liposomal anthracycline formulations have the potential to mitigate cardiotoxicity while improving antitumor efficacy. This overview summarizes the rationale and methodology of cardiac substudies within AAML1831, a randomized Children's Oncology Group Phase 3 study of CPX-351, a liposomal formulation of daunorubicin and cytarabine, in comparison with standard daunorubicin/cytarabine with dexrazoxane in the treatment of pediatric AML.
METHODS/DESIGN
Children (age <22 years) with newly diagnosed AML were enrolled and randomized to CPX-351-containing induction 1 and 2 (Arm A) or standard daunorubicin and dexrazoxane-containing induction (Arm B). Embedded cardiac correlative studies aim to compare the efficacy of this liposomal anthracycline formulation to dexrazoxane for primary prevention of cardiotoxicity by detailed core lab analysis of standardized echocardiograms and serial cardiac biomarkers throughout AML therapy and in follow-up. In addition, AAML1831 will assess the ability of early changes in sensitive echo indices (e.g., global longitudinal strain) and cardiac biomarkers (e.g., troponin and natriuretic peptides) to predict subsequent LVSD. Finally, AAML1831 establishes expert consensus-based strategies in cardiac monitoring and anthracycline dose modification to balance the potentially competing priorities of cardiotoxicity reduction with optimal leukemia therapy.
DISCUSSION
This study will inform diagnostic, prognostic, preventative, and treatment strategies regarding cardiotoxicity during pediatric AML therapy. Together, these measures have the potential to improve leukemia-free and overall survival and long-term cardiovascular health in children with AML. https://clinicaltrials.gov/, identifier NCT04293562.
PubMed: 38107263
DOI: 10.3389/fcvm.2023.1286241 -
Acta Haematologica 2014Children diagnosed with cancer are now living longer as a result of advances in treatment. However, some commonly used anticancer drugs, although effective in curing... (Review)
Review
Children diagnosed with cancer are now living longer as a result of advances in treatment. However, some commonly used anticancer drugs, although effective in curing cancer, can also cause adverse late effects. The cardiotoxic effects of anthracycline chemotherapy, such as doxorubicin, and radiation can cause persistent and progressive cardiovascular damage, emphasizing a need for effective prevention and treatment to reduce or avoid cardiotoxicity. Examples of risk factors for cardiotoxicity in children include higher anthracycline cumulative dose, higher dose of radiation, younger age at diagnosis, female sex, trisomy 21 and black race. However, not all who are exposed to toxic treatments experience cardiotoxicity, suggesting the possibility of a genetic predisposition. Cardioprotective strategies under investigation include the use of dexrazoxane, which provides short- and long-term cardioprotection in children treated with doxorubicin without interfering with oncological efficacy, the use of less toxic anthracycline derivatives and nutritional supplements. Evidence-based monitoring and screening are needed to identify early signs of cardiotoxicity that have been validated as surrogates of subsequent clinically significant cardiovascular disease before the occurrence of cardiac damage, in patients who may be at higher risk.
Topics: Anthracyclines; Antineoplastic Agents; Cardiotonic Agents; Evidence-Based Practice; Gamma Rays; Heart Diseases; Humans; Neoplasms; Risk Factors
PubMed: 25228565
DOI: 10.1159/000360238 -
Cureus Apr 2023Cancer is one of the leading causes of morbidity and mortality in the pediatric population with the most common cancer being acute lymphoblastic leukemia. One of the... (Review)
Review
Cancer is one of the leading causes of morbidity and mortality in the pediatric population with the most common cancer being acute lymphoblastic leukemia. One of the most common drugs used in the treatment is the anthracycline group of chemotherapeutic agents, and a major side effect is cardiotoxicity. Dexrazoxane, a member of the cardioprotective agents' group of medications, is the only current FDA-approved medication to tackle cardiotoxicity. The mechanism of action in which dexrazoxane is cardioprotective is by halting necroptosis in cardiomyocytes after anthracycline therapy and concurrently binds with iron and reduces the formation of anthracycline-iron complexes and reactive oxygen species. The efficacy of dexrazoxane has been demonstrated in clinical trials within the pediatric population with roughly 60%-80% reduction in risk of developing cardiotoxicity with a very tolerable and limited side effect profile. Further research is required to not only establish the efficacy of dexrazoxane within the pediatric population but also to explore other medications that may serve alongside the function of dexrazoxane.
PubMed: 37182052
DOI: 10.7759/cureus.37308 -
Aging Jan 2021Treatment of thoracic tumors with radiotherapy can lead to severe cardiac injury. We investigated the effects of dexrazoxane, a USFDA-approved cardioprotective drug...
Treatment of thoracic tumors with radiotherapy can lead to severe cardiac injury. We investigated the effects of dexrazoxane, a USFDA-approved cardioprotective drug administered with chemotherapy, on radiation-induced heart disease (RIHD) in a rat model. Male Sprague-Dawley rats were irradiated with a single dose of 20 Gy to the heart and treated with dexrazoxane at the time of irradiation and for 12 subsequent weeks. Dexrazoxane suppressed radiation-induced myocardial apoptosis and significantly reversed changes in serum cardiac troponin I levels and histopathological characteristics six months post-radiation. Treatment with dexrazoxane did not alter the radiosensitivity of thoracic tumors in a tumor formation experiment using male nude Balb/C mice with tumors generated by H292 cells. Dexrazoxane reduced the accumulation of reactive oxygen species in rat cardiac tissues, but not in tumors in nude mice. Transcriptome sequencing showed that and , which are involved in Toll-like receptor signaling, may be associated with the anti-RIHD effects of dexrazoxane. Immunohistochemistry revealed that dexrazoxane significantly decreased NF-κB p65 expression in cardiomyocytes. These findings suggest dexrazoxane may protect against RIHD by suppressing apoptosis and oxidative stress in cardiomyocytes.
Topics: Animals; Apoptosis; Dexrazoxane; Heart; Heart Diseases; Male; Mice; Mice, Nude; Protective Agents; Radiation Injuries, Experimental; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species
PubMed: 33406500
DOI: 10.18632/aging.202332 -
The Annals of Pharmacotherapy Jul 2007To review the evidence for the management of anthracycline extravasation and determine the optimal treatment of such injuries. (Review)
Review
OBJECTIVE
To review the evidence for the management of anthracycline extravasation and determine the optimal treatment of such injuries.
DATA SOURCES
A search of MEDLINE (1966-February 2007) and International Pharmaceutical Abstracts (1970-February 2007) was performed using the search terms anthracyclines and extravasation.
DATA SYNTHESIS
Extravasation of anthracyclines can have devastating effects. After infiltration of these drugs into the interstitial tissue, damage may range from mild erythema and pain to severe tissue necrosis. Many agents have been studied in the management of these injuries; however, few have demonstrated efficacy and treatment remains controversial. Nonpharmacologic modalities shown to limit extravasation injuries include local tissue cooling and elevation of the affected area. Corticosteroids, sodium bicarbonate, hyaluronidase, hyperbaric oxygen, heparin fractions, alpha-tocopherol, N-acetylcysteine, and granulocyte macrophage-colony stimulating factor have all either been shown to be ineffective or have limited data supporting their use. Topical dimethyl sulfoxide (DMSO) has been shown in prospective studies to limit the course of extravasation injuries. Dexrazoxane has been shown in animal models and case reports to be useful in the management of anthracycline extravasation. Two recent prospective clinical trials examining intravenous dexrazoxane 1000 mg/m2 within 6 hours of extravasation, 1000 mg/m2 24 hours after extravasation, and 500 mg/m2 48 hours after extravasation injuries add to the data supporting the use of this agent in such injuries. Of the 54 patients enrolled, surgery-requiring necrosis was avoided in 98.2%.
CONCLUSIONS
The optimal treatment of anthracycline extravasation includes local tissue cooling, elevation of the afflicted extremity, dexrazoxane administration, and possibly topical DMSO. Many other drugs have been investigated; however, due to a lack of data, they cannot be recommended for the management of anthracycline extravasation.
Topics: Animals; Anthracyclines; Antibiotics, Antineoplastic; Disease Management; Enzyme Inhibitors; Extravasation of Diagnostic and Therapeutic Materials; Humans
PubMed: 17550954
DOI: 10.1345/aph.1H700 -
Paediatric Drugs Oct 2014In the US, children diagnosed with cancer are living longer, but not without consequences from the same drugs that cured their cancer. In these patients, cardiovascular... (Review)
Review
In the US, children diagnosed with cancer are living longer, but not without consequences from the same drugs that cured their cancer. In these patients, cardiovascular disease is the leading cause of non-cancer-related morbidity and mortality. Although this review focuses on anthracycline-related cardiomyopathy in childhood cancer survivors, the global lifetime risk of other cardiovascular diseases such as atherosclerosis, arrhythmias and intracardiac conduction abnormalities, hypertension, and stroke also are increased. Besides anthracyclines, newer molecularly targeted agents, such as vascular endothelial growth factor receptor and tyrosine kinase inhibitors, also have been associated with acute hypertension, cardiomyopathy, and increased risk of ischemic cardiac events and arrhythmias, and are summarized here. This review also covers other risk factors for chemotherapy-related cardiotoxicity (including both modifiable and non-modifiable factors), monitoring strategies (including both blood and imaging-based biomarkers) during and following cancer treatment, and discusses the management of cardiotoxicity (including prevention strategies such as cardioprotection by use of dexrazoxane).
Topics: Anthracyclines; Antineoplastic Agents; Cardiomyopathies; Cardiotonic Agents; Cardiotoxicity; Child; Humans; Neoplasms; Risk Factors; Survivors
PubMed: 25134924
DOI: 10.1007/s40272-014-0085-1