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Archives of Pharmacal Research Oct 2022Chemotherapy is a main treatment for cancer, and it benefits patients by controlling cancer relapse and metastasis, thereby leading to an increase in the overall... (Review)
Review
Chemotherapy is a main treatment for cancer, and it benefits patients by controlling cancer relapse and metastasis, thereby leading to an increase in the overall survival rate. However, this treatment is associated with mild to severe side effects, one of which is cardiotoxicity. The severity of cardiotoxicity, a leading cause of cardiovascular diseases, depends on the type of cancer therapy employed and the time required for its management. A chemotherapeutic agent is used either alone or in combination with other drugs for cancer treatment. The exact mechanism of chemotherapeutic agent-induced cardiotoxicity remains unclear, although it is likely to be multifactorial and to include oxidative stress, apoptosis, and inflammation. There are many approaches to avoid the untoward effects of chemotherapeutic agents. However, the available options for cardiac protection are minimal, and they include renin-angiotensin system blockers, beta-blockers, herbal drugs, or iron chelators such as dexrazoxane. The present review provides information on the molecular mechanism of chemotherapy-induced myocardial infarction and cardiotoxicity along with scientifically studied synthetic molecules, herbal extracts, and natural products to manage chemotherapy-induced cardiotoxicity.
Topics: Humans; Cardiotoxicity; Antineoplastic Agents; Heart; Neoplasms; Oxidative Stress; Cardiotonic Agents
PubMed: 36306018
DOI: 10.1007/s12272-022-01411-4 -
Supportive Care in Cancer : Official... May 2015Extravasation is a potentially severe complication that can occur during the administration of chemotherapy. The scarcity of evidence available makes it difficult to... (Review)
Review
BACKGROUND
Extravasation is a potentially severe complication that can occur during the administration of chemotherapy. The scarcity of evidence available makes it difficult to develop an optimal management scheme. The purpose of this guideline is to review the relevant scientific literature on the prevention, management, and treatment of extravasation occurring during the administration of chemotherapy to cancer patients.
METHOD
A scientific literature review was conducted using the PubMed search tool. The period covered was from database inception to April 2014, inclusively. Since the literature on extravasation treatment is often empirical, anecdotal, and controversial, the review also identified clinical practice guidelines and expert consensuses published by relevant international organizations and cancer agencies.
RESULTS
Identification of potential risk factors and preventive measures can reduce the risk of extravasation. Recognition and management of symptoms are crucial in patients with this complication. Provision of adequate instruction to personnel responsible for administering chemotherapy and to patients on recognizing symptoms, preventing, and managing extravasation is essential. Extravasation can be treated with dry warm or cold compresses and various antidotes such as dimethyl sulfoxide, dexrazoxane, hyaluronidase, or sodium thiosulfate, depending on the agent that has caused extravasation. Patient monitoring to assess the progression or regression of symptoms and to thus take the appropriate measures is necessary.
CONCLUSION
Several strategies must be established to ensure that extravasation is recognized and properly managed. Given the evidence available at this time, the Comité de l'évolution des pratiques en oncologie (CEPO) has made recommendations for clinical practice in Quebec.
Topics: Antineoplastic Agents; Catheterization, Central Venous; Catheterization, Peripheral; Dexrazoxane; Dimethyl Sulfoxide; Extravasation of Diagnostic and Therapeutic Materials; Humans; Hyaluronoglucosaminidase; Neoplasms; Quebec; Risk Factors; Thiosulfates
PubMed: 25711653
DOI: 10.1007/s00520-015-2635-7 -
Biomedicine & Pharmacotherapy =... Jun 2017Doxorubicin (DOX) is an anthracycline antibiotic, which is effectively used in the treatment of different malignancies, such as leukemias and lymphomas. Its most serious... (Review)
Review
Doxorubicin (DOX) is an anthracycline antibiotic, which is effectively used in the treatment of different malignancies, such as leukemias and lymphomas. Its most serious side effect is dose-dependent cardiotoxicity, which occurs through inducing oxidative stress apoptosis. Due to the myelosuppressive effect of dexrazoxane, a commonly-used drug to alleviate DOX-induced cardiotoxicity, researchers investigated the potential of phytochemicals for prophylaxis and treatment of this condition. Phytochemicals are plant chemicals that have protective or disease preventive properties. Preclinical trials have shown antioxidant properties for several plant extracts, such as those of Aerva lanata, Aronia melanocarpa, Astragalus polysaccharide, and Bombyx mori plants. Other plant extracts showed an ability to inhibit apoptosis, such as those of Astragalus polysaccharide, Azadirachta indica, Bombyx mori, and Allium stavium plants. Unlike synthetic agents, phytochemicals do not impair the clinical activity of DOX and they are particularly safe for long-term use. In this review, we summarized the results of preclinical trials that investigated the cardioprotective effects of phytochemicals against DOX-induced cardiotoxicity. Future human trials are required to translate these cardioprotective mechanisms into practical clinical implications.
Topics: Animals; Cardiotoxicity; Doxorubicin; Heart; Humans; Phytochemicals; Protective Agents
PubMed: 28460429
DOI: 10.1016/j.biopha.2017.04.033 -
Chemico-biological Interactions Oct 2023Cyclophosphamide (CYP) is extensively used in tumor therapy, but its clinical application is limited by its toxic effects on the bladder. Since CYP-induced cystitis is...
Cyclophosphamide (CYP) is extensively used in tumor therapy, but its clinical application is limited by its toxic effects on the bladder. Since CYP-induced cystitis is believed to be mediated by acrolein (ACR), a product of lipid peroxidation that triggers ferroptosis, we hypothesized that ferroptosis might be an essential molecular mechanism underlying CYP-induced cystitis. The purpose of this study was to test this hypothesis. Intraperitoneal injection of CYP led to bladder hemorrhage and edema, along with increased oxidation, inflammation, and cell injury. Further analysis revealed these changes were associated with altered ferroptosis markers in the bladder, such as FPN1, ACSL4, SLC7A11, and GPX4, indicating the existence of ferroptosis. Administration of ferroptosis inhibitor dexrazoxane (DXZ) improved ferroptosis and prevented CYP-induced pathological changes in the bladder. Collectively, our study revealed that ferroptosis is an important mechanism underlying CYP-induced cystitis, and therapeutic approaches targeting ferroptosis could be developed to treat CYP-induced cystitis.
PubMed: 37690746
DOI: 10.1016/j.cbi.2023.110701 -
Expert Opinion on Pharmacotherapy Oct 2022Anthracycline chemotherapeutic agents are widely used in the treatment of hematological and solid tumors, working principally through DNA intercalation and topoisomerase... (Review)
Review
INTRODUCTION
Anthracycline chemotherapeutic agents are widely used in the treatment of hematological and solid tumors, working principally through DNA intercalation and topoisomerase II inhibition. However, they are also well known to have cardiotoxic sequelae, commonly denoted as a reduction in ejection fraction. Drug-associated cardiotoxicity remains a significant limiting factor in the use of anthracyclines.
AREAS COVERED
In this review, we explore the potential mechanisms of anthracycline-associated cardiotoxicity, identifying high-risk cohorts and approaches to cardiovascular monitoring. The mechanisms through which cardiotoxicity occurs are complex and diverse, ultimately leading to increased oxidative stress, mitochondrial dysfunction, and subsequent cellular apoptosis. Many of the cardiotoxic effects of anthracyclines exhibit a dose-dependent cumulative relationship and are more apparent in patients with previously existing cardiovascular risk factors. Long-term cardiovascular monitoring and optimization of risk factors, prior to commencing treatment as well as beyond the time of treatment, is therefore essential.
EXPERT OPINION
We discuss some of the pharmacological strategies proposed to mitigate anthracycline-associated cardiotoxicity as well as prevention strategies to reduce the burden of coexisting cardiovascular risk factors. We highlight methods of early detection of patient cohorts who are at increased risk of developing anthracycline-associated cardiotoxicity and identify potential avenues for further research.
Topics: Humans; Anthracyclines; Cardiotoxicity; Topoisomerase II Inhibitors; Antibiotics, Antineoplastic; Neoplasms; DNA Topoisomerases, Type II; DNA
PubMed: 36102190
DOI: 10.1080/14656566.2022.2124107 -
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 -
Journal of Oncology Pharmacy Practice :... Jul 2020Mitoxantrone is a chemotherapeutic agent approved for various diseases. The literature has been conflicting in classifying mitoxantrone as a vesicant or irritant.
INTRODUCTION
Mitoxantrone is a chemotherapeutic agent approved for various diseases. The literature has been conflicting in classifying mitoxantrone as a vesicant or irritant.
CASE REPORT
We report a patient who had an extravasation of mitoxantrone. Mitoxantrone was administered in 50 ml normal saline. After mitoxantrone was completely infused, the site appeared edematous and the blue color of mitoxantrone developed beneath the skin. The patient reported pain. The extravasation was treated with dexrazoxane and cold compresses. The pain improved each day. However, blistering developed five weeks later and the patient ultimately required surgical intervention for debridement and grafting.
DISCUSSION
Extravasation events are rare and there are few controlled studies. Because of the similarities in chemical structures and mechanism of actions between mitoxantrone and anthracyclines, mitoxantrone extravasation is often treated similar to anthracyclines. Mitoxantrone's classification is unclear, as some literature classifies it as a vesicant and others as an irritant. Our case supports the categorization of mitoxantrone as a vesicant.
Topics: Aged; Antineoplastic Agents; Cryotherapy; Extravasation of Diagnostic and Therapeutic Materials; Humans; Infusions, Intravenous; Male; Mitoxantrone
PubMed: 31902285
DOI: 10.1177/1078155219893736 -
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 -
Current Drug Metabolism 2017Anthracycline antibiotic doxorubicin (DOX) is a very potent and extensively prescribed chemotherapeutic drug. It is widely utilized in the therapy of variety of... (Review)
Review
BACKGROUND
Anthracycline antibiotic doxorubicin (DOX) is a very potent and extensively prescribed chemotherapeutic drug. It is widely utilized in the therapy of variety of haematological and solid tumours, although its administration is commonly accompanied with several severe side effects. The most serious one is a development of dose-dependent and cumulative cardiotoxicity. In the course of time, many strategies have been investigated in order to avoid or at least to diminish DOX-induced cardiac dysfunction; these include reduction of toxic effect by coadministration with iron chelators (dexrazoxane), trastuzumab, taxanes, statins, and ACE-inhibitors. However, the attenuation of cardiotoxic effect is still not satisfactory yet.
OBJECTIVE
This review represents an overall appraisal of studies concerning with the utilization of various doxorubicinloaded nanoparticles in the cancer treatment with specific emphasis on those studies evaluating their influence on the reduction of heart tissue damage.
CONCLUSION
Introduction of nanoscale drug delivery systems undoubtedly represents nowadays one of the most promising tools for lowering systemic toxicity. Nanoparticles enable to target the therapeutic payload directly towards the tumor tissue, thus leading to the increased accumulation of the drug in the desired tissue and simultaneously protecting surrounding healthy tissues.
Topics: Animals; Antibiotics, Antineoplastic; Cardiotoxicity; Doxorubicin; Drug Carriers; Humans; Nanoparticles; Neoplasms
PubMed: 28059036
DOI: 10.2174/1389200218666170105165444