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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 -
Anti-cancer Drugs Aug 2017Dexrazoxane is indicated as a cardioprotective agent for patients receiving doxorubicin who are at increased risk for cardiotoxicity. Concerns have been raised on the...
Dexrazoxane is indicated as a cardioprotective agent for patients receiving doxorubicin who are at increased risk for cardiotoxicity. Concerns have been raised on the use of dexrazoxane, particularly in adjuvant therapy, because of the risk of interference with the antitumor effect of doxorubicin. Two meta-analyses in metastatic breast cancer have rejected this hypothesis, but have shown an apparent increase in the severity of myelosuppression when dexrazoxane is used. Here, we analyzed retrospectively a cohort of our institute database to assess whether the addition of dexrazoxane causes more bone marrow suppression in breast cancer patients receiving doxorubicin-based adjuvant therapy. The secondary objectives were assessment of the incidence of febrile neutropenia, dose-schedule modifications, recorded cardiac events or cardiac test abnormalities, and overall survival. Eight hundred and twenty-two female patients who received adjuvant (or neoadjuvant) doxorubicin and cyclophosphamide for breast cancer between 2001 and 2013 were included. One hundred and four of these patients also received dexrazoxane concurrently with the adjuvant treatment. Hospital records and, when accessible, community clinic records were reviewed. The median follow-up duration was 7 years for patients receiving dexrazoxane and 7.5 years for patients not receiving dexrazoxane. 85.6% of patients were alive at data lock. Compared with the nondexrazoxane group, patients who received dexrazoxane were older (median age at diagnosis 59 vs. 52 years) and more likely to receive dose-dense AC therapy (73 vs. 59%) and adjuvant trastuzumab treatment (29 vs. 15%). Compared with the nondexrazoxane group, dexrazoxane treatment was associated with a higher rate of hematological side effects: leukopenia (48 vs. 39%), neutropenia (45 vs. 31%, P=0.003), anemia (86 vs. 73%, P=0.005), and thrombocytopenia (37 vs. 22%, P=0.001). There were more febrile neutropenia hospitalizations (20 vs. 10%, P=0.001) and dose reductions (22 vs. 8%, P<0.001) in the dexrazoxane group, but no significant difference in the incidence of treatment delays or cancellations. The incidence of cardiac events was the same in both treatment groups with and without dexrazoxane. There was a nonsignificantly lower mortality rate in the dexrazoxane group (9.6%) compared with the nondexrazoxane group (15.0%) at data lock. Adding dexrazoxane to doxorubicin in adjuvant therapy patients leads to higher rates of bone marrow suppression in all blood components, as well as more febrile neutropenia events, and dose reductions. No differences in events defined as cardiac toxicities were detected. Dexrazoxane had no detrimental effect on survival, despite the higher hematological toxicity, the older median age, and the higher prevalence of HER2-positive disease in the dexrazoxane group.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cohort Studies; Cyclophosphamide; Dexrazoxane; Doxorubicin; Female; Humans; Middle Aged; Retrospective Studies; Survival Analysis
PubMed: 28562379
DOI: 10.1097/CAD.0000000000000514 -
Journal of Clinical Oncology : Official... Feb 1996
Topics: Adult; Animals; Antibiotics, Antineoplastic; Cardiovascular Agents; Child; Heart; Heart Diseases; Humans; Neoplasms; Razoxane
PubMed: 8636740
DOI: 10.1200/JCO.1996.14.2.332 -
Seminars in Oncology Nursing Feb 2011To present a clinical update on the prevention, detection, and evidence-based management of vesicant chemotherapy extravasations. (Review)
Review
OBJECTIVE
To present a clinical update on the prevention, detection, and evidence-based management of vesicant chemotherapy extravasations.
DATA SOURCES
Journal articles, published and unpublished case reports, personal experience.
CONCLUSION
In the 4 years that have elapsed since the publication of the original article, much more is known about vesicant chemotherapy extravasation, and effective evidence-based treatments now are available. The antidotes sodium thiosulfate for mechlorethamine extravasations and hyaluronidase for plant alkaloid extravasations are recommended by the manufacturers of these vesicants and cited in nursing guidelines. The anthracycline extravasation treatment dexrazoxane for injection, the first and only extravasation treatment with proven effectiveness, is now available as Totect (dexrazoxane; TopoTarget USA, Rockaway, NJ, USA) in the US and Savene (SpePharm, Amsterdam, The Netherlands) in Europe.
IMPLICATIONS FOR NURSING PRACTICE
Nurses who administer vesicant chemotherapy agents need to be aware of the most current evidence (or lack of evidence) for various types of extravasation treatment. Well-informed nurses are patient advocates and instrumental in detecting, managing, and documenting extravasations. Most importantly, nurses play a key role in preventing vesicant chemotherapy extravasations.
Topics: Antineoplastic Agents; Extravasation of Diagnostic and Therapeutic Materials; Female; Forecasting; Humans; Infusions, Intravenous; Male; Oncology Nursing; Practice Guidelines as Topic
PubMed: 21255716
DOI: 10.1016/j.soncn.2010.11.010 -
Ameliorating anthracycline cardiotoxicity in children with cancer: clinical trials with dexrazoxane.Seminars in Oncology Aug 1998Anthracyclines have major activity against a broad range of childhood cancers. Concern over the risk of long-term cardiotoxicity associated with their use has called... (Review)
Review
Anthracyclines have major activity against a broad range of childhood cancers. Concern over the risk of long-term cardiotoxicity associated with their use has called into question the role of these agents in the frontline treatment of many patients. Dexrazoxane was developed as a specific cardioprotectant "antidote" which can prevent anthracycline cardiotoxicity without inhibiting its antitumor effect. To date, four clinical trials of dexrazoxane have been conducted in pediatric cancer patients (primarily with sarcomas). The two largest series, conducted at the National Cancer Institute Pediatric Branch, demonstrated significant short-term cardioprotection with no evidence of interference with antitumor activity. Additional clinical trials are ongoing, or planned to open shortly, to better evaluate the role of dexrazoxane in the treatment of childhood cancer. These studies, being conducted on larger numbers of patients with better prospects for cure, are expected to definitviely answer the outstanding questions of whether preventing short-term, subclinical cardiotoxicity will translate into long-term cardioprotection, and whether the use of dexrazoxane interferes with the anti-tumor efficacy of doxorubicin-containing regimens.
Topics: Anthracyclines; Antineoplastic Agents; Cardiovascular Agents; Child; Clinical Trials as Topic; Heart Diseases; Humans; Razoxane
PubMed: 9768829
DOI: No ID Found -
Journal of Korean Medical Science Sep 2010This study attempted to assess the incidence and outcome of anthracycline cardiotoxicity and the role of dexrazoxane as a cardioprotectant in childhood solid tumors. The...
This study attempted to assess the incidence and outcome of anthracycline cardiotoxicity and the role of dexrazoxane as a cardioprotectant in childhood solid tumors. The dexrazoxane group included 47 patients and the control group of historical cohort included 42. Dexrazoxane was given in the 10:1 ratio to doxorubicin. Fractional shortening and systolic and diastolic left ventricular diameters were used to assess the cardiac function. The median follow-ups were 54 months in the dexrazoxane group and 86 months in the control group. The mean cumulative doses of doxorubicin were 280.8+/-83.4 mg/m(2) in the dexrazoxane group and 266.1+/-75.0 mg/m(2) in the control group. The dexrazoxane group experienced significantly fewer cardiac events (27.7% vs. 52.4%) and less severe congestive heart failure (6.4% vs. 14.3%) than the control group. Thirteen cardiotoxicities including one cardiac death and 2 congestive heart failures occurred in the dexrazoxane group, and 22 cardiotoxicities including 2 cardiac deaths and 4 congestive heart failures, in the control group. Five year cardiac event free survival rates were 69.2% in the dexrazoxane group and 45.8% in the control group (P=0.04). Dexrazoxane reduces the incidence and severity of early and late anthracycline cardiotoxicity in childhood solid tumors.
Topics: Adolescent; Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Child; Child, Preschool; Cohort Studies; Disease-Free Survival; Doxorubicin; Echocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Infant; Male; Neoplasms; Razoxane; Ventricular Function, Left
PubMed: 20808678
DOI: 10.3346/jkms.2010.25.9.1336 -
JACC. CardioOncology Apr 2024
PubMed: 38774009
DOI: 10.1016/j.jaccao.2024.01.004 -
Clinical Cancer Research : An Official... Jul 2021Doxorubicin cardiac toxicity is widely misunderstood, largely preventable, and starts with the first dose. This article reviews the history of doxorubicin cardiac...
Doxorubicin cardiac toxicity is widely misunderstood, largely preventable, and starts with the first dose. This article reviews the history of doxorubicin cardiac toxicity and strategies for minimizing it. Dexrazoxane cardioprotection can safely be initiated on day 1 without compromising antitumor activity, allowing doxorubicin administration beyond the reported maximum lifetime dose..
Topics: Cardiotoxicity; Dexrazoxane; Doxorubicin; Humans; Razoxane; Sarcoma
PubMed: 33990361
DOI: 10.1158/1078-0432.CCR-21-1376 -
PloS One 2023[This corrects the article DOI: 10.1371/journal.pone.0294848.].
[This corrects the article DOI: 10.1371/journal.pone.0294848.].
PubMed: 38117773
DOI: 10.1371/journal.pone.0296372 -
Medizinische Klinik (Munich, Germany :... Jul 2007Antineoplastic chemotherapy may induce acute or late side effects. Cytostatic-induced cardiomyopathy counts as one of the most dangerous side effects and has major... (Review)
Review
BACKGROUND
Antineoplastic chemotherapy may induce acute or late side effects. Cytostatic-induced cardiomyopathy counts as one of the most dangerous side effects and has major implications for the use of anthracyclines. Since anthracyclines are widely employed and frequently indispensable cytostatics, it is important to elucidate the mechanisms and risk factors of the associated heart failure and develop preventive or interventional strategies.
RESULTS
Anthracycline-induced cardiomyopathy has been reported in up to 85% of treated patients. Known risk factors are younger age, advanced age, female gender, preexisting cardiac illness, cardiac irradiation, and other concomitant cardiotoxic medications. Proposed preventive strategies include the development of new anthracyclines, longer anthracycline infusion times, liposomal anthracycline formulations, the application of the iron chelator dexrazoxane, and identification of predisposing gene variants.
CONCLUSION
Most promising preventive strategies include longer infusion times, liposomal formulations, and the administration of the iron chelator dexrazoxane.
Topics: Anthracyclines; Antineoplastic Agents; Cardiomyopathies; Heart Failure; Humans
PubMed: 17634876
DOI: 10.1007/s00063-007-1071-y