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Journal of Clinical Oncology : Official... Apr 2013
Topics: Female; Heart Diseases; Humans; Neoplasms
PubMed: 23439750
DOI: 10.1200/JCO.2012.46.9908 -
Cancer Feb 2022The objective of this study was to examine long-term outcomes among children newly diagnosed with cancer who were treated in dexrazoxane-containing clinical trials. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The objective of this study was to examine long-term outcomes among children newly diagnosed with cancer who were treated in dexrazoxane-containing clinical trials.
METHODS
P9404 (acute lymphoblastic leukemia/lymphoma [ALL]), P9425 and P9426 (Hodgkin lymphoma), P9754 (osteosarcoma), and Dana-Farber Cancer Institute 95-01 (ALL) enrolled 1308 patients between 1996 and 2001: 1066 were randomized (1:1) to doxorubicin with or without dexrazoxane, and 242 (from P9754) were nonrandomly assigned to receive dexrazoxane. Trial data were linked with the National Death Index, the Organ Procurement and Transplantation Network, the Pediatric Health Information System (PHIS), and Medicaid. Osteosarcoma survivors from the Childhood Cancer Survivor Study (CCSS; n = 495; no dexrazoxane) served as comparators in subanalyses. Follow-up events were assessed with cumulative incidence, Cox regression, and Fine-Gray methods.
RESULTS
In randomized trials (cumulative prescribed doxorubicin dose, 100-360 mg/m ; median follow-up, 18.6 years), dexrazoxane was not associated with relapse (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63-1.13), second cancers (HR, 1.19; 95% CI, 0.62-2.30), all-cause mortality (HR, 1.07; 95% CI, 0.78-1.47), or cardiovascular mortality (HR, 1.45; 95% CI, 0.41-5.16). Among P9754 patients (all exposed to dexrazoxane; cumulative doxorubicin, 450-600 mg/m ; median follow-up, 16.6-18.4 years), no cardiovascular deaths or heart transplantation occurred. The 20-year heart transplantation rate among CCSS osteosarcoma survivors (mean doxorubicin, 377 ± 145 mg/m ) was 1.6% (vs 0% in P9754; P = .13). Among randomized patients, serious cardiovascular outcomes (cardiomyopathy, ischemic heart disease, and stroke) ascertained by PHIS/Medicaid occurred less commonly with dexrazoxane (5.6%) than without it (17.6%; P = .02), although cardiomyopathy rates alone did not differ (4.4% vs 8.1%; P = .35).
CONCLUSIONS
Dexrazoxane did not appear to adversely affect long-term mortality, event-free survival, or second cancer risk.
Topics: Child; Dexrazoxane; Doxorubicin; Follow-Up Studies; Hodgkin Disease; Humans; Outcome Assessment, Health Care; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 34644414
DOI: 10.1002/cncr.33974 -
Revista Portuguesa de Cardiologia :... Jun 2016The increasing use of anthracyclines, together with the longer survival of cancer patients, means the toxic effects of these drugs need to be monitored. In order to... (Review)
Review
The increasing use of anthracyclines, together with the longer survival of cancer patients, means the toxic effects of these drugs need to be monitored. In order to detect, prevent or mitigate anthracycline-induced cardiomyopathy, it is essential that all patients undergo a rigorous initial cardiovascular assessment, followed by close monitoring. Several clinical trials have shown the cardioprotective effect of non-pharmacological measures such as exercise, healthy lifestyles, control of risk factors and treatment of comorbidities; a cardioprotective effect has also been observed with pharmacological measures such as beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, statins, dexrazoxane and liposomal formulations. However, there are currently no guidelines for managing prevention in these patients. In this review the authors discuss the state of the art of the assessment, monitoring, and, above all, the prevention of anthracycline-induced cardiotoxicity.
Topics: Anthracyclines; Antineoplastic Agents; Cardiomyopathies; Cardiotoxicity; Humans; Neoplasms
PubMed: 27255173
DOI: 10.1016/j.repc.2015.12.004 -
Current Opinion in Pediatrics Oct 2018We review the cardiotoxic chemotherapeutic agents, the clinical and subclinical presentations and progression of their cardiotoxicity, and the management of the... (Review)
Review
PURPOSE OF REVIEW
We review the cardiotoxic chemotherapeutic agents, the clinical and subclinical presentations and progression of their cardiotoxicity, and the management of the subsequent cardiovascular disease in survivors of childhood cancer. We discuss various preventive measures, especially the cardioprotectant, dexrazoxane, whose use with anthracycline chemotherapy, including doxorubicin, is based on strong evidence. Most treatment recommendations for this unique population are based on expert opinion, not on empirical evidence.
RECENT FINDINGS
As patients with childhood cancers live longer, morbidity from the cardiac side effects of chemotherapy is increasing. Treatment-related cardiac damage is irreversible and often progressive. It is imperative that such damage be prevented with strategies such as limiting the cumulative anthracycline dose, the use of anthracycline structural analogues and the use of cardioprotective agents.
SUMMARY
A deeper understanding of the mechanisms of their cardiotoxicity reveals that there is no 'safe' dose of anthracyclines. However, certain risk factors, such as higher lifetime anthracycline cumulative doses, higher anthracycline dose rates, female sex, longer follow-up, younger age at anthracycline treatment and cardiac irradiation, are associated with more severe cardiotoxicity. We advocate the use of dexrazoxane to limit the cardiotoxic effects of anthracycline chemotherapy.
Topics: Adult Survivors of Child Adverse Events; Anthracyclines; Antineoplastic Agents; Cancer Survivors; Cardiotonic Agents; Cardiotoxicity; Cardiovascular Diseases; Dexrazoxane; Humans
PubMed: 30124579
DOI: 10.1097/MOP.0000000000000675 -
International Journal of Clinical... Mar 2013Extravasation is recognised as a major complication of administering intravenous chemotherapy treatment. Of the agents involved in extravasation, anthracyclines are... (Review)
Review
Extravasation is recognised as a major complication of administering intravenous chemotherapy treatment. Of the agents involved in extravasation, anthracyclines are associated with the greatest risk to patients because they are vesicant agents, having the potential to cause blistering and ulceration. If not identified and left untreated, anthracycline extravasation can lead to more serious complications such as tissue necrosis and functional impairment. Dexrazoxane (Savene(®) ) is the only licensed antidote for the treatment of anthracycline extravasation and clinical evidence has shown Savene(®) to be highly effective for preventing the need for surgery following anthracycline extravasation, allowing full recovery in the majority of patients. To date, there have been eight published studies reporting a total of 102 cases of Savene(®) use. Here, we review the published data on the efficacy of Savene(®) and present an analysis of 12 UK case studies. All UK oncology centres where Savene(®) has been used to manage anthracycline extravasation were contacted by SpePharm UK, who requested case studies for this publication. All of the cases received, including two from our own experience of using Savene(®) have been included in the analysis.
Topics: Adult; Aged; Anthracyclines; Antidotes; Antineoplastic Agents; Breast Neoplasms; Chelating Agents; Esophageal Neoplasms; Extravasation of Diagnostic and Therapeutic Materials; Female; Humans; Male; Middle Aged; Razoxane
PubMed: 23409691
DOI: 10.1111/ijcp.12103 -
Journal of Cancer Research and Clinical... Jan 2004This article summarizes the views of an expert meeting of cardiologists and oncologists on the use of dexrazoxane in anthracycline-based chemotherapy.... (Review)
Review
This article summarizes the views of an expert meeting of cardiologists and oncologists on the use of dexrazoxane in anthracycline-based chemotherapy. Anthracycline-induced cardiotoxicity remains a major concern and new trends in treatment (e.g., combination of an anthracycline with other agents) will ensure that it remains a problem. Dexrazoxane reduces this cardiotoxicity in adults and children with a range of tumor types. Further research may help to identify those patients who are at particular risk of cardiotoxicity and who would benefit the most from dexrazoxane. There are also numerous possibilities for dexrazoxane in other clinical situations, which must be addressed in future trials.
Topics: Anthracyclines; Antibiotics, Antineoplastic; Cardiotonic Agents; Heart; Humans; Razoxane
PubMed: 14564513
DOI: 10.1007/s00432-003-0498-7 -
JACC. CardioOncology Sep 2019The authors performed a systematic review and meta-analysis of randomized and nonrandomized trials on the efficacy of dexrazoxane in patients with breast cancer who were...
OBJECTIVES
The authors performed a systematic review and meta-analysis of randomized and nonrandomized trials on the efficacy of dexrazoxane in patients with breast cancer who were treated with anthracyclines with or without trastuzumab.
BACKGROUND
Breast cancer treatment with anthracyclines and trastuzumab is associated with an increased risk of cardiotoxicity. Among the various strategies to reduce the risk of cardiotoxicity, dexrazoxane is an option for primary prevention, but it is seldom used in clinical practice.
METHODS
Online databases were searched from January 1990 up to March 1, 2019, for clinical trials on the use of dexrazoxane for the prevention of cardiotoxicity in patients with breast cancer receiving anthracyclines with or without trastuzumab. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model meta-analysis.
RESULTS
Seven randomized trials and 2 retrospective trials with a total of 2,177 patients were included. Dexrazoxane reduced the risk of clinical heart failure (RR: 0.19; 95% CI: 0.09 to 0.40; p < 0.001) and cardiac events (RR: 0.36; 95% CI: 0.27 to 0.49; p < 0.001) irrespective of previous exposure to anthracyclines. The rate of a partial or complete oncological response, overall survival, and progression-free survival were not affected by dexrazoxane.
CONCLUSIONS
Dexrazoxane reduced the risk of clinical heart failure and cardiac events in patients with breast cancer undergoing anthracycline chemotherapy with or without trastuzumab and did not significantly impact cancer outcomes. However, the quality of available evidence is low, and further randomized trials are warranted before the systematic implementation of this therapy in clinical practice.
PubMed: 34396164
DOI: 10.1016/j.jaccao.2019.08.003 -
Current Medicinal Chemistry Feb 1998The bisdioxopiperazine dexrazoxane (ICRF-187) has proven to be clinically very effective in reducing the cardiotoxicity of doxorubicin and other anthracyclines.... (Review)
Review
The bisdioxopiperazine dexrazoxane (ICRF-187) has proven to be clinically very effective in reducing the cardiotoxicity of doxorubicin and other anthracyclines. Doxorubicin is thought to exert its toxicity through iron-based oxygen free radical-induced oxidative stress on the relatively unprotected cardiac muscle. Upon hydrolysis, dexrazoxane forms a compound similar to ethylenediaminetetraacetic acid (EDTA) which, like EDTA, is a strong chelator of iron. Dexrazoxane presumably exerts its cardioprotective effects by either binding free or loosely bound iron, or iron complexed to doxorubicin, thus preventing or reducing site-specific oxygen radical production that damages cellular components. The chemistry, biochemistry, and cell biology of dexrazoxane and other bisdioxopiperazines are discussed. The pre-clinical studies demonstrating the protective effects of dexrazoxane against toxicities caused by doxorubicin, other anthracyclines, bleomycin, alloxan, acetaminophen, and oxygen are also discussed. In vitro and in vivo studies of the cardioprotective and other effects of other bisdioxopiperazines are also covered. Also discussed are the anti-metastatic and radiosensitization effects of razoxane and dexrazoxane. The current clinical status of dexrazoxane in preventing anthracycline-induced toxicities in both adult and pediatric patients is reviewed.
Topics: Animals; Anthracyclines; Doxorubicin; Heart; Iron Chelating Agents; Molecular Structure; Oxidative Stress; Piperazines; Razoxane
PubMed: 9481032
DOI: No ID Found -
Supportive Care in Cancer : Official... Jul 1996The dose-limiting toxicity of the widely used anticancer agent, doxorubicin, is a destructive, irreversible and progressive cardiomyopathy. Prevention of this... (Review)
Review
The dose-limiting toxicity of the widely used anticancer agent, doxorubicin, is a destructive, irreversible and progressive cardiomyopathy. Prevention of this cardiotoxicity without reduction of antitumour efficacy or the production of new toxicities has therefore been a long-time therapeutic goal. It has now been largely achieved by prior administration of dexrazoxane (DXRz; Cardioxane in Europe; Zinecard in North America; ICRF 187). Six randomized, controlled clinical trials in breast and lung cancer and in soft tissue sarcomas of children have shown a 90% reduction in doxorubicin-induced cardiotoxicity. The results of all these trials lead to the conclusion that DXRz permits: (1) cardiotoxic doses of doxorubicin to be given without cardiotoxicity; (2) patients with increased cardiac risk factors to be treated with full doses of dioxorubicin; (3) second-line treatment with other cardiotoxic drugs.
Topics: Adult; Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Child; Child, Preschool; Clinical Trials as Topic; Dose-Response Relationship, Drug; Doxorubicin; Female; Humans; Male; Neoplasms; Razoxane; Treatment Outcome
PubMed: 8829310
DOI: 10.1007/BF01358885 -
British Journal of Clinical Pharmacology Mar 2017This article is part of a joint Themed section with the British Journal of Pharmacology on Cardiotoxicity. The rest of the Themed section will appear in a future issue... (Review)
Review
This article is part of a joint Themed section with the British Journal of Pharmacology on Cardiotoxicity. The rest of the Themed section will appear in a future issue of BJP and will be available at http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1476-5381 The number of survivors of childhood cancers has increased exponentially over the past few decades. However, these survivors are also at substantially increased long-term risk of morbidity and mortality, especially from treatment-related cardiotoxicity. Preventing these risks is now a priority when treating children and adolescents with cancer. Dexrazoxane reduces the risk of anthracycline-induced cardiotoxicity among adults and children with cancer without reducing its antineoplastic effects or event-free survival. Thus, it should be strongly considered as a part of therapy for children and adolescents treated with anthracyclines.
Topics: Anthracyclines; Antibiotics, Antineoplastic; Cancer Survivors; Cardiotonic Agents; Cardiotoxicity; Dexrazoxane; Humans; Models, Cardiovascular
PubMed: 27591829
DOI: 10.1111/bcp.13120