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Nederlands Tijdschrift Voor Geneeskunde 2010Cardiotoxicity and extravasation injuries are extremely serious complications of anthracycline use. Both complications are probably caused by oxidative stress.... (Review)
Review
Cardiotoxicity and extravasation injuries are extremely serious complications of anthracycline use. Both complications are probably caused by oxidative stress. Dexrazoxane has been approved as a cardioprotective agent and as an antidote in extravasation of anthracyclines. Randomized clinical trials have shown that dexrazoxane is the only cardioprotective agent proven to be effective in the treatment of anthracycline-induced cardiotoxicity. In these clinical studies dexrazoxane decreased the incidence of cardiac events and heart failure. Possible adverse effects of dexrazoxane when administered as a cardioprotective agent are a decreased antitumor effect of anthracyclines and the onset of secondary malignancies in children. As an antidote in anthracycline extravasation, clinical studies showed dexrazoxane to be highly efficacious in preventing the need for surgical resection. Dexrazoxane can be considered as the treatment of first choice for this indication. Dexrazoxane is well tolerated in general. The most commonly reported side effects are leukopenia, thrombocytopenia and local reactions at the infusion site.
Topics: Anthracyclines; Cardiovascular Agents; Heart Diseases; Heart Failure; Humans; Randomized Controlled Trials as Topic; Razoxane
PubMed: 20619024
DOI: No ID Found -
The Annals of Pharmacotherapy Sep 1994To review doxorubicin-induced cardiotoxicity and to evaluate the use of dexrazoxane in its prevention. (Comparative Study)
Comparative Study Review
OBJECTIVE
To review doxorubicin-induced cardiotoxicity and to evaluate the use of dexrazoxane in its prevention.
DATA SOURCES
All animal and human reports involving doxorubicin-induced cardiac adverse effects were searched using MEDLINE combined with a fan search of relevant papers.
DATA EXTRACTION
Animal, in vitro cellular, and human data are thoroughly reviewed with particular emphasis on doxorubicin-induced cardiotoxicity, including clinical manifestations, risk factors, and mechanisms of toxicity. The role of dexrazoxane in the prevention of doxorubicin-induced cardiotoxicity is reviewed, including mechanism of effect, animal data, and human trials.
DATA SYNTHESIS
Anthracyclines are associated with a cumulative, dose-dependent, irreversible cardiomyopathy that can lead to congestive heart failure and death. The incidence of cardiotoxicity rises sharply at a total lifetime dose of more than 550 mg/m2. Through its semiquinone metabolite, doxorubicin appears to generate superoxide anion and superhydroxide free radicals with iron as a cofactor. Because of poor myocardial concentrations of superoxide dismutase, catalase, and glutathione peroxidase, these free radicals cause extensive lipid peroxidation and mitochondrial destruction.
CONCLUSIONS
Dexrazoxane is hydrolyzed to its active form intracellularly and binds iron to prevent the formation of superhydroxide radicals, thus preventing mitochondrial destruction. The effect of dexrazoxane on the prevention of doxorubicin-induced cardiotoxicity is impressive in both animal and human studies. Further research is needed to clearly demonstrate the effect dexrazoxane has on the antitumor effects of combination chemotherapy while defining optimal dosing strategies to minimize myelosuppression and maximize cardioprotection.
Topics: Animals; Cardiomyopathies; Dogs; Doxorubicin; Drug Synergism; Humans; Randomized Controlled Trials as Topic; Rats; Razoxane; Swine; Swine, Miniature
PubMed: 7803884
DOI: 10.1177/106002809402800912 -
Expert Review of Cardiovascular Therapy Nov 2008Dexrazoxane is a derivative of the powerful metal-chelating agent ethyl enediamine tetra acetic acid. Its cardioprotective effect is thought to be due to its ability to... (Review)
Review
Dexrazoxane is a derivative of the powerful metal-chelating agent ethyl enediamine tetra acetic acid. Its cardioprotective effect is thought to be due to its ability to chelate iron and reduce the number of metal ions complexed with anthracycline and, consequently, decrease the formation of superoxide radicals. Preclinical studies have confirmed that dexrazoxane has significant activity as a cardioprotective agent against anthracycline-induced cardiotoxicity. Dexrazoxane is well-tolerated, with myelosuppression being the dose-limiting toxicity in Phase I trials. The cardioprotective utility of dexrazoxane has been further illustrated in a number of randomized trials. In addition no significant difference in survival has been observed between the dexrazoxane and control arms of these trials but, in one, a significantly lower response rate was observed in the dexrazoxane compared to placebo arm. Further trials are required to evaluate the efficacy of dexrazoxane in hematological malignancies as well as the adjuvant treatment of breast cancer. Its use in the paediatric setting and in the management of elderly patients with cardiac comorbidity also requires investigation. Recently, interest has focused on the use of dexrazoxane as an antidote for anthracycline extravasation. In addition the general cytoprotective activity of this drug requires further assessment, as well as selectivity in this context.
Topics: Aged; Animals; Anthracyclines; Antibiotics, Antineoplastic; Bone Marrow; Cardiotonic Agents; Chelating Agents; Child; Clinical Trials as Topic; Drug Evaluation, Preclinical; Heart Diseases; Humans; Neoplasms; Razoxane
PubMed: 19018683
DOI: 10.1586/14779072.6.10.1311 -
Cardiovascular Toxicology 2007Dexrazoxane is highly effective in reducing anthracycline-induced cardiotoxicity and extravasation injury and is used clinically for these indications. Dexrazoxane has... (Review)
Review
Dexrazoxane is highly effective in reducing anthracycline-induced cardiotoxicity and extravasation injury and is used clinically for these indications. Dexrazoxane has two biological activities: it is a prodrug that is hydrolyzed to an iron chelating EDTA-type structure and it is also a strong inhibitor of topoisomerase II. Doxorubicin is able to be reductively activated to produce damaging reactive oxygen species. Iron-dependent cellular damage is thought to be responsible for its cardiotoxicity. The available experimental evidence supports the conclusion that dexrazoxane reduces doxorubicin cardiotoxicity by binding free iron and preventing site-specific oxidative stress on cardiac tissue. However, it cannot be ruled out that dexrazoxane may also be protective through its ability to inhibit topoisomerase II.
Topics: Animals; Antineoplastic Agents; Cardiovascular Agents; Clinical Trials as Topic; Doxorubicin; Enzyme Inhibitors; Heart Diseases; Humans; Neoplasms; Prodrugs; Razoxane; Topoisomerase II Inhibitors
PubMed: 17652819
DOI: 10.1007/s12012-007-0023-3 -
Drugs 2005Dexrazoxane (Cardioxane, Zinecard, a cyclic derivative of edetic acid, is a site-specific cardioprotective agent that effectively protects against anthracycline-induced... (Meta-Analysis)
Meta-Analysis Review
Dexrazoxane (Cardioxane, Zinecard, a cyclic derivative of edetic acid, is a site-specific cardioprotective agent that effectively protects against anthracycline-induced cardiac toxicity. Dexrazoxane is approved in the US and some European countries for cardioprotection in women with advanced and/or metastatic breast cancer receiving doxorubicin; in other countries dexrazoxane is approved for use in a wider range of patients with advanced cancer receiving anthracyclines. As shown in clinical trials, intravenous dexrazoxane significantly reduces the incidence of anthracycline-induced congestive heart failure (CHF) and adverse cardiac events in women with advanced breast cancer or adults with soft tissue sarcomas or small-cell lung cancer, regardless of whether the drug is given before the first dose of anthracycline or the administration is delayed until cumulative doxorubicin dose is > or =300 mg/m2. The drug also appears to offer cardioprotection irrespective of pre-existing cardiac risk factors. Importantly, the antitumour efficacy of anthracyclines is unlikely to be altered by dexrazoxane use, although the drug has not been shown to improve progression-free and overall patient survival. At present, the cardioprotective efficacy of dexrazoxane in patients with childhood malignancies is supported by limited data. The drug is generally well tolerated and has a tolerability profile similar to that of placebo in cancer patients undergoing anthracycline-based chemotherapy, with the exception of a higher incidence of severe leukopenia (78% vs 68%; p < 0.01). Dexrazoxane is the only cardioprotective agent with proven efficacy in cancer patients receiving anthracycline chemotherapy and is a valuable option for the prevention of cardiotoxicity in this patient population.
Topics: Anthracyclines; Antineoplastic Agents; Cardiovascular Agents; Cardiovascular Diseases; Humans; Neoplasms; Randomized Controlled Trials as Topic; Razoxane
PubMed: 15892593
DOI: 10.2165/00003495-200565070-00008 -
Current Heart Failure Reports Jun 2012Anthracycline-based chemotherapeutics have long been recognized as effective agents for treating a wide range of malignancies. However, their use is not without... (Review)
Review
Anthracycline-based chemotherapeutics have long been recognized as effective agents for treating a wide range of malignancies. However, their use is not without significant adverse cardiotoxic side effects. Strategies for prevention involve limiting free-radical production and subsequent cardiac myocyte damage. Dexrazoxane remains the most widely studied cardioprotective medication. Alternative agents may reduce cardiotoxicity but may still cause significant cardiovascular problems. The role of β-blockers and angiotensin-converting enzyme inhibitors in the treatment of heart failure is well proven. The role of these medications in the prevention and treatment of chemotherapy-induced cardiotoxicity is not well established.
Topics: Anthracyclines; Antineoplastic Agents; Heart Failure; Humans; Population Surveillance; Practice Guidelines as Topic
PubMed: 22382639
DOI: 10.1007/s11897-012-0083-y -
British Journal of Nursing (Mark Allen...This article reviews the efficacy and place in therapy of dexrazoxane (Savene®) for the treatment of anthracycline extravasation, highlighting the lack of inclusion of... (Review)
Review
AIMS
This article reviews the efficacy and place in therapy of dexrazoxane (Savene®) for the treatment of anthracycline extravasation, highlighting the lack of inclusion of Savene in most UK cancer network and organisational treatment guidelines. Here we offer advice to nurses on making a case to ensure the availability of Savene.
KEY FINDINGS
In 2010, the UK National Extravasation Information Service (NEXIS) green card scheme reported that anthracyclines were the second most common agent involved in extravasations, but they carry the greatest risk to the patient because of their potentially serious consequences. Anthracycline extravasations therefore require prompt and effective treatment. Due to the infrequent occurrence of anthracycline extravasations, their accidental nature and ethical considerations, conducting randomised controlled clinical trials in this therapy area is not possible. As treatment decisions should always be made on patient-specific factors, health professionals need to demonstrate the rationale for choosing a particular course of action when presented with an anthracycline extravasation, especially when we are moving into an era of increased medical litigation. There are several possible treatment options, some of which require demonstrable local core competencies in order to be considered for a particular patient. Based on the available evidence, Savene-the only licensed antidote-is recommended as an effective management strategy for anthracycline extravasation and should be made available in all settings where chemotherapy is administered. However, a high percentage of nurses administering chemotherapy still do not have access to Savene, as it has not been included in their local guidelines for the management of extravasations. Thus, in a large part of the UK, this important treatment option is not available, leaving a significant unmet need (Figure 1).
CONCLUSIONS
As nurses play a key role in the prevention, detection, and management of extravasations, they should also assume a key role in ensuring that their local protocols include all appropriate management strategies. Where appropriate, if Savene is not included in the treatment guidelines, nurses should feel empowered to encourage their trust and Specialist Commissioning Groups (SCGs) to make it available, and thus minimise the serious risks associated with anthracycline extravasations.
Topics: Anthracyclines; Antineoplastic Agents; Dexrazoxane; Extravasation of Diagnostic and Therapeutic Materials; Humans; Neoplasms; Oncology Nursing; Practice Guidelines as Topic; Risk Factors; Topoisomerase II Inhibitors; United Kingdom
PubMed: 24067273
DOI: 10.12968/bjon.2013.22.Sup17.S6 -
JACC. CardioOncology Apr 2024
PubMed: 38774009
DOI: 10.1016/j.jaccao.2024.01.004 -
Pediatric Blood & Cancer Jun 2023Cardiovascular disease is the leading cause of non-malignant morbidity and mortality in childhood cancer survivors (CCSs). Anthracyclines are included in many treatment...
Cardiovascular disease is the leading cause of non-malignant morbidity and mortality in childhood cancer survivors (CCSs). Anthracyclines are included in many treatment regimens for paediatric cancer, but unfortunately, these compounds are cardiotoxic. One in 10 CCSs who has received an anthracycline will develop a symptomatic cardiac event over time. Given the crucial need to mitigate anthracycline-related cardiotoxicity (ARC), the authors critically examined published data to identify effective cardioprotective strategies. Based on their expert analysis of contemporary literature data, it was concluded that consideration should be given for routine use of dexrazoxane in children with cancer who are at risk of ARC.
PubMed: 37355856
DOI: 10.1002/pbc.30515 -
Cardiology Clinics Nov 2019Left ventricular systolic dysfunction (LVSD) and overt heart failure are well known manifestations of chemotherapy-induced cardiotoxicity. The development of LVSD is... (Review)
Review
Left ventricular systolic dysfunction (LVSD) and overt heart failure are well known manifestations of chemotherapy-induced cardiotoxicity. The development of LVSD is clinically significant because it can impact the delivery of lifesaving chemotherapy and increase the risk of developing heart failure, compromising quality of life and survival years after cure of the cancer. Cancer treatment-related cardiomyopathy is most commonly associated with anthracyclines and trastuzumab. Several interventions have been identified to prevent cancer-induced cardiomyopathy. Anthracyclines is a major culprit, and prevention strategies with limiting cumulative dose, continuous infusion, dexrazoxane, and liposomal formulation have been shown to decrease the risk of cardiotoxicity.
Topics: Antineoplastic Agents; Cardiomyopathies; Cardiotoxicity; Humans; Neoplasms; Practice Guidelines as Topic; Primary Prevention
PubMed: 31587785
DOI: 10.1016/j.ccl.2019.07.009