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Anti-cancer Drugs Oct 2018The extravasation of chemotherapeutic agents is a challenge for oncologic care teams. The management of nonliposomal (conventional) anthracyclines is well established in... (Review)
Review
The extravasation of chemotherapeutic agents is a challenge for oncologic care teams. The management of nonliposomal (conventional) anthracyclines is well established in clinical practice guidelines, including general measures and specific antidotes, such as dexrazoxane. However, there is little scientific evidence on the management of liposomal and pegylated liposomal anthracyclines. The aim of this paper was to review the scientific literature on the extravasation of liposomal and pegylated liposomal anthracyclines and determine the clinical impact of this type of extravasation, focusing on dexrazoxane. The literature was searched using two databases: PubMed and Embase. Three searches were conducted, using liposomal anthracycline extravasation, pegylated liposomal anthracycline extravasation, and liposomal doxorubicin extravasation as keywords, respectively. Seven articles fulfilled the study eligibility criteria and included seventeen cases in humans. Extravasation occurred with three drugs: liposomal doxorubicin in nine (53%) patients, liposomal daunorubicin in four (23.5%) patients, and pegylated liposomal doxorubicin in four (23.5%) patients. General measures for extravasations were applied in all patients, but only three patients received dexrazoxane. All cases were completely resolved at 2-3 months, except for one patient, in whom dexrazoxane was not used. In animals, dexrazoxane decreased both the frequency of wounds produced by pegylated liposomal doxorubicin and their extent. The pharmacokinetic profiles of liposomal and pegylated liposomal anthracyclines differ from those of conventional anthracyclines, modifying their effectiveness and safety. General measures may be inadequate to heal areas affected by extravasation, which may require the administration of dexrazoxane. However, each case should be evaluated individually for the administration of dexrazoxane in off-label use until scientific evidence is available on its effectiveness and safety as an antidote for these formulations of anthracyclines.
Topics: Animals; Anthracyclines; Antibiotics, Antineoplastic; Daunorubicin; Dexrazoxane; Doxorubicin; Extravasation of Diagnostic and Therapeutic Materials; Humans; Liposomes; Polyethylene Glycols
PubMed: 30036190
DOI: 10.1097/CAD.0000000000000672 -
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 -
British Journal of Pharmacology Jul 2020Retraction: Spagnuolo, R., Recalcati, S., Tacchini, L., and Cairo, G. (2011), Role of hypoxia-inducible factors in the dexrazoxane-mediated protection of cardiomyocytes...
Retraction: Spagnuolo, R., Recalcati, S., Tacchini, L., and Cairo, G. (2011), Role of hypoxia-inducible factors in the dexrazoxane-mediated protection of cardiomyocytes from doxorubicin-induced toxicity. British Journal of Pharmacology, 163: 299-312. https://doi.org/10.1111/j.1476-5381.2011.01208.x The above article, published online on January 14, 2011, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal's Editor-in-Chief, Professor Amrita Ahluwalia, the British Pharmacological Society, and John Wiley & Sons Ltd. The retraction has been agreed due to the duplication of Figures 1A and 3A, which overlap with figures appearing in another article published by the authors in the Journal of Leukocyte Biology in 2008. The authors state that due to the time elapsed, they are unable to provide evidence of the original data.
PubMed: 32512636
DOI: 10.1111/bph.15097 -
La Clinica Terapeutica 1998We performed a randomized trial to evaluate the cardioprotective effect of dexrazoxane (DEX) in advanced breast cancer patients (ABC) treated with high single-dose... (Clinical Trial)
Clinical Trial Randomized Controlled Trial Review
PURPOSE
We performed a randomized trial to evaluate the cardioprotective effect of dexrazoxane (DEX) in advanced breast cancer patients (ABC) treated with high single-dose epirubicin (EPI). A secondary objective was to determine the role of radioimmunoscintigraphy (RIS) in the assessment of epirubicin cardiotoxicity.
PATIENTS AND METHODS
Ninety-five patients with ABC were treated with EPI 160 mg/m2 by i.v. bolus every 3 weeks with or without DEX, 1,000 mg/m2 i.v. Cardiac monitoring included multigated radionuclide (MUGA) scan with determination of resting left ventricular ejection fraction (LVEF), and RIS with 111-Indium antimyosin monoclonal antibodies.
RESULTS
The overall response rate was 69% in the EPI arm and 67% in the EPI + DEX arm; median time to response and median time to progression were identical in both arms, being 2 and 8 months, respectively. Median survival was 19 months versus 29 months (p 0.21), respectively. DEX did not appear to contribute to extracardiac EPI toxicity. Congestive heart failure occurred only in the EPI arm (2 instances). LVEF significantly decreased from baseline only in the EPI group. An abnormal tracer uptake at RIS was observed early in both arms, but the increase in heart to lung ratio was much more evident in the control group.
CONCLUSIONS
DEX significantly protects against the development of high dose epirubicin cardiotoxicity apparently without evidence of an adverse impact on antitumor activity and non cardiac toxicity. RIS is a very sensitive technique in detecting anthracycline cardiac damage, but its specificity is low and cannot be considered alone a primary test for guiding anthracycline treatment.
Topics: Aged; Aged, 80 and over; Angiocardiography; Antibiotics, Antineoplastic; Breast Neoplasms; Cardiovascular Agents; Dose-Response Relationship, Drug; Epirubicin; Female; Heart; Heart Diseases; Humans; Neoplasm Staging; Radionuclide Imaging; Razoxane
PubMed: 9621483
DOI: No ID Found -
Seminars in Oncology Aug 1998Dexrazoxane is a synthetic bisdiketopiperazine two-ringed compound which hydrolyzes to an EDTA analog. These rings undergo intracellular hydrolysis to form the single... (Review)
Review
Dexrazoxane is a synthetic bisdiketopiperazine two-ringed compound which hydrolyzes to an EDTA analog. These rings undergo intracellular hydrolysis to form the single and double (ICRF-198) chelating forms of the compound by both enzymatic and non-enzymatic catalysis. These dexrazoxane metabolites are efficient at stripping the cations from the iron:anthracycline complex. The disruption of the complex prevents the oxidative damage from free radicals promoted by this anthracycline complex. Pharmacologic studies of single agent dexrazoxane (originally studied as an antineoplastic agent) demonstrates an alpha half-life of approximately 30 minutes and a beta half-life of 2 to 4 hours. When given in combination with anthracyclines (e.g. doxorubicin or epirubicin) the pharmacokinetics of dexrazoxane are unchanged. Additional studies of anthracycline metabolism when given in combination with dexrazoxane, both in single arm and randomized cross-over studies, have generally shown no change in anthracycline metabolism, including pharmacokinetic parameters of alpha, beta, and gamma half-lives, area-under-the-curve, or clearance. There is no pharmacokinetic interaction of dexrazoxane on anthracycline metabolism and, therefore, pharmacokinetics cannot account for the cardioprotective effects described for dexrazoxane.
Topics: Animals; Anthracyclines; Antineoplastic Agents; Cardiovascular Agents; Clinical Trials as Topic; Evaluation Studies as Topic; Humans; Iron Chelating Agents; Razoxane
PubMed: 9768822
DOI: No ID Found -
Seminars in Oncology Aug 1998Dexrazoxane prevents the dose-limiting cardiotoxicity of the anthracyclines without reducing their antitumor efficacy and without new adverse side effects. Dexrazoxane... (Review)
Review
Dexrazoxane prevents the dose-limiting cardiotoxicity of the anthracyclines without reducing their antitumor efficacy and without new adverse side effects. Dexrazoxane reduces the severity of gastrointestinal symptoms of the anthracycline containing combination doxorubicin, 5-fluorouracil, cyclophosphamide and most surprisingly and importantly, dexrazoxane increases the median survival time of advanced breast cancer responders to the doxorubicin, 5-fluorouracil, cyclophosphamide regimen. The median survival time is doubled as compared to controls to nearly 3 years.
Topics: Adult; Anthracyclines; Antineoplastic Agents; Breast Neoplasms; Cardiovascular Agents; Child; Clinical Trials as Topic; Heart Diseases; Humans; Razoxane
PubMed: 9768824
DOI: No ID Found -
Dexrazoxane for the prevention of cardiomyopathy in anthracycline treated pediatric cancer patients.Pediatric Blood & Cancer Jun 2005Anthracyclines play a major role in chemotherapeutic regimens for a variety of childhood cancers, but produce dose-related cardiotoxicity. Dexrazoxane, a chelating agent... (Review)
Review
Anthracyclines play a major role in chemotherapeutic regimens for a variety of childhood cancers, but produce dose-related cardiotoxicity. Dexrazoxane, a chelating agent that binds iron intracellularly, has been cautiously included in anthracycline-based regimens. Our understanding of anthracycline and dexrazoxane pharmacokinetics in children is very limited. In addition, the administration schedule used for adults (bolus dexrazoxane prior to bolus anthracycline) may not be the best to attain both short- and long-term cardioprotection. Dexrazoxane could diminish the anti-tumor activity of and/or increase toxicities from anthracyclines. Pediatric oncologists must be assured this intervention does not diminish the success in curing children with cancer.
Topics: Anthracyclines; Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Child; Humans; Neoplasms; Razoxane
PubMed: 15700251
DOI: 10.1002/pbc.20358 -
Postepy Higieny I Medycyny... 2006The nthracycline antibiotics are among the most widely used and effective anticancer drugs. The therapeutic efficacy of this class of drugs is limited by cumulative... (Review)
Review
The nthracycline antibiotics are among the most widely used and effective anticancer drugs. The therapeutic efficacy of this class of drugs is limited by cumulative cardiac toxicity. Dexrazoxane is the only clinically approved cardioprotective agent used in anthracycline-containing anticancer therapy. Its cardioprotective action allows the use of a much higher cumulative dose of anthracyclines and improvement in the effectiveness of treatment. Anthracyclines form complexes with iron ions, which are very active in the production of reactive oxygen species responsible for the lipid peroxidation of mitochondrial and endoplasmatic reticulum membranes. This process seems to be the major cause of anthracycline-induced cardiotoxicity. Dexrazoxane exerts its protective effects by rapid and complete binding of ferric and ferrous ions, even by displacing the metal ions from complexes with anthracyclines. Besides its cardioprotective effect, dexrazoxane also exhibits anticancer properties. Like other derivatives of bisdioxopiperazine, dexrazoxane is a catalytic inhibitor of eukaryotic DNA topoisomerase II, the key enzyme controlling DNA topology and contributing to the replication and transcription processes. Dexrazoxane is able to lock topoisomerase II at the stage of the enzyme reaction cycle where the enzyme forms a closed clamp around the DNA. This phenomenon seems to be the main reason for the generation of DNA double-strand breaks by dexrazoxane as well as its cytotoxicity against quickly proliferating cancer cells. Other effects of its topoisomerase II catalytic inhibition is the induction of cell differentiation and apoptosis. Dexrazoxane may be used not only as a cardioprotective agent, but also as a modulator of action of some anticancer drugs by enhancing their selectivity or by delaying the development of multidrug resistance.
Topics: Anthracyclines; Antibiotics, Antineoplastic; Cardiomyopathies; Cardiovascular Agents; Chelating Agents; Neoplasms; Razoxane
PubMed: 17115008
DOI: No ID Found -
JACC. CardioOncology Apr 2024
PubMed: 38773999
DOI: 10.1016/j.jaccao.2024.02.004 -
Expert Opinion on Investigational Drugs Feb 2008The use of the anthracycline anticancer drugs doxorubicin, daunorubicin, epirubicin and idarubicin sometimes results in accidental extravasation injury and can be a... (Review)
Review
BACKGROUND
The use of the anthracycline anticancer drugs doxorubicin, daunorubicin, epirubicin and idarubicin sometimes results in accidental extravasation injury and can be a serious complication of their use.
OBJECTIVE
The object of this review was to evaluate the preclinical and clinical literature on the use of dexrazoxane in preventing anthracycline-induced extravasation injury.
METHODS
A review of the literature was carried out using PubMed.
RESULTS/CONCLUSIONS
Dexrazoxane, which is clinically used to reduce doxorubicin-induced cardiotoxicity, has been shown in two clinical studies and in several case reports to be highly efficacious in preventing anthracycline-induced extravasation injury. Dexrazoxane is a prodrug analog of the metal chelator EDTA that likely acts by removing iron from the iron-anthracycline complex, thus preventing formation of damaging reactive oxygen species.
Topics: Animals; Anthracyclines; Antineoplastic Agents; Cardiotonic Agents; Extravasation of Diagnostic and Therapeutic Materials; Humans; Razoxane
PubMed: 18230055
DOI: 10.1517/13543784.17.2.217