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Medicinal Research Reviews Mar 2016Mitoxantrone is a synthetic anthracenedione originally developed to improve the therapeutic profile of the anthracyclines and is commonly applied in the treatment of... (Review)
Review
Mitoxantrone is a synthetic anthracenedione originally developed to improve the therapeutic profile of the anthracyclines and is commonly applied in the treatment of breast and prostate cancers, lymphomas, and leukemias. A comprehensive overview of the drug's molecular, biochemical, and cellular pharmacology is presented here, beginning with the cardiotoxic nature of its predecessor doxorubicin and how these properties shaped the pharmacology of mitoxantrone itself. Although mitoxantrone is firmly established as a DNA topoisomerase II poison within mammalian cells, it is now clear that the drug interacts with a much broader range of biological macromolecules both covalently and noncovalently. Here, we consider each of these interactions in the context of their wider biological relevance to cancer therapy and highlight how they may be exploited to further enhance the therapeutic value of mitoxantrone. In doing so, it is now clear that mitoxantrone is more than just another topoisomerase II poison.
Topics: Animals; Antineoplastic Agents; Clinical Trials as Topic; Drug Discovery; Drug Resistance, Neoplasm; Humans; Mitoxantrone; Topoisomerase II Inhibitors
PubMed: 26286294
DOI: 10.1002/med.21364 -
Molecules (Basel, Switzerland) Oct 2016Mitoxantrone is a synthetic anticancer drug used clinically in the treatment of different types of cancer. It was developed as a doxorubicin analogue in a program to... (Review)
Review
Mitoxantrone is a synthetic anticancer drug used clinically in the treatment of different types of cancer. It was developed as a doxorubicin analogue in a program to find drugs with improved antitumor activity and decreased cardiotoxicity compared with the anthracyclines. As the cell membrane is the first barrier encountered by anticancer drugs before reaching the DNA sites inside the cells and as surfactant micelles are known as simple model systems for biological membranes, the drugs-surfactant interaction has been the subject of great research interest. Further, quantitative understanding of the interactions of drugs with biomimicking structures like surfactant micelles may provide helpful information for the control of physicochemical properties and bioactivities of encapsulated drugs in order to design better delivery systems with possible biomedical applications. The present review describes the physicochemical aspects of the interactions between the anticancer drug mitoxantrone and different surfactants. Mitoxantrone-micelle binding constants, partitions coefficient of the drug between aqueous and micellar phases and the corresponding Gibbs free energy for the above processes, and the probable location of drug molecules in the micelles are discussed.
Topics: Antineoplastic Agents; Cell Membrane; Micelles; Mitoxantrone; Models, Biological; Models, Molecular; Surface-Active Agents
PubMed: 27754390
DOI: 10.3390/molecules21101356 -
Clinical Pharmacy Aug 1988The chemistry, pharmacology, pharmacokinetics, clinical efficacy, dosage and administration, and adverse effects of mitoxantrone are reviewed. Mitoxantrone, an... (Clinical Trial)
Clinical Trial Review
The chemistry, pharmacology, pharmacokinetics, clinical efficacy, dosage and administration, and adverse effects of mitoxantrone are reviewed. Mitoxantrone, an aminoanthraquinone that was synthesized in 1979, belongs to a new chemical class of agents known as the anthracenediones. It possesses antiviral, antibacterial, immunomodulatory, and antitumor activity. The drug's antitumor activity is attributed to its interaction with DNA topoisomerase II, and its interaction with human cells may also involve nonintercalary, electrostatic interactions. Mitoxantrone is poorly absorbed orally and is most commonly administered intravenously. The drug is rapidly distributed into the red blood cells, white blood cells, and platelets, followed by deep-tissue sequestration. Mitoxantrone has demonstrated clinical efficacy in the treatment of leukemia, lymphoma, and breast cancer. As a single agent, mitoxantrone has a response rate of roughly 30% in acute nonlymphocytic leukemia or acute myeloid leukemia. In combination with other standard agents (cytarabine, vincristine, and prednisone), the response rate may reach 60%. In breast cancer, mitoxantrone's response rate as a single agent is 25-30%, while combination regimens produce response rates of 60% or more. The drug can cause cardiotoxicity with cumulative doses. Other adverse effects include myelosuppression, nausea and vomiting, stomatitis, mucositis, and alopecia. The cost of mitoxantrone is comparable to that of doxorubicin, but it is substantially more expensive than daunorubicin. Mitoxantrone is an important new agent with antitumor activity in leukemia, lymphoma, and breast cancer. In most situations, mitoxantrone will be considered second-line treatment or a restricted-use item because of its high cost and because of the lack of FDA approval for indications other than acute nonlymphocytic leukemia.
Topics: Animals; Breast Neoplasms; Clinical Trials as Topic; Drug Evaluation; Humans; Leukemia; Lymphoma; Mitoxantrone; Neoplasms
PubMed: 3048848
DOI: No ID Found -
Multiple Sclerosis (Houndmills,... Jul 1996Mitoxantrone, a cytotoxic agent recently developed, was subsequently found a very potent immunosuppressor. Experimental data in experimental allergic encephaloymyelitis... (Review)
Review
Mitoxantrone, a cytotoxic agent recently developed, was subsequently found a very potent immunosuppressor. Experimental data in experimental allergic encephaloymyelitis demonstrated a dramatic suppression of both active and passive forms. Immune effects concern cellular and humoral components and are particularly persistent. B cell subset is preferentially deleted. Suppressor cells are relatively spared and suppression becomes dominant. In cancer therapy, the main advantages of mitoxantrone are a definitely better immediate tolerance and very low delayed adverse reactions (carcinogenicity, teratogenicity, impact on reproductive organs). Given its major immunosuppressive activity and its better tolerance, mitoxantrone was a potential candidate for multiple sclerosis therapy. Several clinical trials have confirmed the remarkable efficacy of mitoxantrone to reduce both attack and progression rates. Unfortunately the cardiotoxicity was found more frequent than expected and limits the maximum cumulative dose to 120 mg/m2. Mitoxantrone, when employed properly, may be useful in patients with frequent and disabling excerbations and/or rapidly progressing disability. It must be kept in mind that multiple sclerosis is a chronic disease, and that the benefit is limited to the period of administration of any treatment.
Topics: Antineoplastic Agents; Clinical Trials as Topic; Encephalomyelitis, Autoimmune, Experimental; Humans; Immunosuppressive Agents; Mitoxantrone; Multiple Sclerosis; Randomized Controlled Trials as Topic
PubMed: 9345411
DOI: 10.1177/135245859600100608 -
The Cochrane Database of Systematic... Oct 2005Mitoxantrone (MX) has been shown to be moderately effective in reducing the clinical outcome measures of disease activity in multiple sclerosis (MS) patients. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mitoxantrone (MX) has been shown to be moderately effective in reducing the clinical outcome measures of disease activity in multiple sclerosis (MS) patients.
OBJECTIVES
The objective was to assess the efficacy and safety of MX in relapsing-remitting MS (RRMS), progressive relapsing MS (PRMS) and secondary progressive MS (SPMS).
SEARCH STRATEGY
We searched the Cochrane MS Group Trials Register (searched April 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2004), MEDLINE (Pub Med) (January 1966 to April 2005), EMBASE (January 1974 to April 2005), and reference lists of articles. We also undertook hand searching and contacting trialists and pharmaceutical companies.
SELECTION CRITERIA
The trials were selected if double-blinded, placebo-controlled, randomised, irrespective of eventual additive therapy (such as steroids).
DATA COLLECTION AND ANALYSIS
Three reviewers independently selected articles for inclusion, assessed trials' quality and extracted data.
MAIN RESULTS
Four trials involving 270 participants were included. MX was found to reduce the progression of disability at 2 years follow-up (proportion of participants with 6-months confirmed progression of disability: Odds Ratios (OR) 0.3, p = 0.05). Similar figures were found regarding the reduction in annualised relapse rate and the proportion of patients free from relapses at 1 and 2 years, as well as the number of patients with active MRI lesions at 6 months/ 1 year only. Side effects reported in the trials were more frequent in treated patients than in controls. Caution must be exercised in drawing conclusions from such data because of the heterogeneous quality and characteristics of the included trials, which are different in terms of treatment schedule and type of enrolled patients. More than half of the included patients came from a single study. Moreover, from the included trials, it was not possible to estimate the long-term efficacy and safety of MX, which may raise concerns about the risk of cardiotoxicity and therapy-related leukemias, which is increasingly reported in the literature.
AUTHORS' CONCLUSIONS
MX is moderately effective in reducing the disease progression and the frequency of relapses in patients affected by RR, PR and SP MS in the short-term follow-up (2 years), even if the results are based on trials heterogeneous in terms of drug dosage and inclusion criteria. No major neoplastic or symptomatic cardiotoxicity related to MX have been reported from the trials. However, longer follow-up studies are highly warranted to better explore the efficacy and safety of the drug, mainly as regards the long-term risk of therapy-related leukemias and cardiotoxicity. As a conclusion, MX has a partial efficacy, but, due to its unclear long-term safety profile, it should be used to treat patients with worsening RR and SP MS with evidence of worsening disability.
Topics: Humans; Immunosuppressive Agents; Mitoxantrone; Multiple Sclerosis; Randomized Controlled Trials as Topic
PubMed: 16235298
DOI: 10.1002/14651858.CD002127.pub2 -
Neurology Dec 2004Patients with worsening relapsing-remitting multiple sclerosis (MS), secondary progressive MS, and progressive relapsing MS are potential candidates for treatment with... (Review)
Review
Patients with worsening relapsing-remitting multiple sclerosis (MS), secondary progressive MS, and progressive relapsing MS are potential candidates for treatment with mitoxantrone. Early identification of these patients is essential because there is emerging evidence that early and aggressive treatment might delay or limit long-term disability. Treatment with mitoxantrone is associated with certain adverse events, such as cardiotoxicity. However, the possible benefits of treatment (e.g., reduction in disease progression) outweigh the risks for patients with aggressive or worsening disease. With the selection of appropriate patients and careful monitoring for adverse events, mitoxantrone can be safely administered.
Topics: Contraindications; Drug Administration Schedule; Humans; Immunosuppressive Agents; Mitoxantrone; Multiple Sclerosis; Patient Education as Topic; Patient Selection
PubMed: 15623666
DOI: 10.1212/wnl.63.12_suppl_6.s25 -
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 -
Biochemical and Biophysical Research... Oct 2022Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a common nutritional metabolic disease in poultry that seriously compromises the health of chickens and...
Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a common nutritional metabolic disease in poultry that seriously compromises the health of chickens and reduces the economic benefits of the industry. In this study, we investigated the therapeutic effect of mitoxantrone (MTX) on hepatic steatosis in broilers. We constructed a steatosis cell model in vitro by adding oleic acid and palmitic acid to chicken hepatocytes (LMH cells), to examine influence of MTX on fat deposition on LMH cells. To determine the effects of MTX on hepatic steatosis in broiler livers in vivo, broilers were fed a high-fat diet to establish a fatty liver model. Our data show that MTX reduced the triglyceride (TG) levels and total cholesterol levels in LMH cells. In the MAFLD chick model, MTX decreased mRNA abundance of hepatic-lipid-synthesis-related gene such as FASN and increased mRNA abundance of fatty-acid-β-oxidation-related genes such as CPT1, PPARα, and reduced hepatic TG levels. MTX also reduced serum lipid and the percentage of abdominal fat. These results suggest that MTX improves hepatic steatosis in broilers as well as reduces circulating lipid levels and fat accumulation in broilers. Our work provides a promising therapeutic strategy for MAFLD and excessive fat accumulation in broiler chickens.
Topics: Animals; Chickens; Diet, High-Fat; Fatty Liver; Lipid Metabolism; Lipids; Liver; Mitoxantrone; RNA, Messenger
PubMed: 36007336
DOI: 10.1016/j.bbrc.2022.08.042 -
Neurological Sciences : Official... Oct 2009Mitoxantrone (MTX) is a synthetic antineoplastic cytotoxic drug, active both on proliferative and non-proliferative cells. The efficacy of MTX has been suggested by many... (Review)
Review
Mitoxantrone (MTX) is a synthetic antineoplastic cytotoxic drug, active both on proliferative and non-proliferative cells. The efficacy of MTX has been suggested by many open-label or observational studies and demonstrated in four randomized controlled clinical trials (RCTs). It is indicated for reducing neurological disability and the frequency of clinical relapses in patients with progressive relapsing and worsening relapsing-remitting MS patients. The short-term most frequent adverse events observed in RCTs have been nausea/vomiting, alopecia, an increased risk of urinary and respiratory tract infections, phlebitis, transitory leukopenia, amenorrhea in female patients and infertility. However, the most serious risks of the drug are represented by potential cardiotoxicity and leukaemia, whose incidence seems to be higher than previously reported. Therefore, all potential serious adverse events should be carefully considered against the potential relevant benefits of MTX treatment on every single MS patient.
Topics: Humans; Magnetic Resonance Imaging; Mitoxantrone; Multiple Sclerosis; Risk Assessment
PubMed: 19882368
DOI: 10.1007/s10072-009-0142-7 -
Expert Review of Neurotherapeutics Jun 2014Mitoxantrone is an immunosuppressive drug approved for aggressive relapsing and progressive multiple sclerosis. In recent years, its use has decreased due to the risk of... (Review)
Review
Mitoxantrone is an immunosuppressive drug approved for aggressive relapsing and progressive multiple sclerosis. In recent years, its use has decreased due to the risk of severe adverse events and the introduction of novel therapies, such as natalizumab or fingolimod. Mitoxantrone is effective in reducing inflammatory activity by decreasing the number of relapses and MRI lesions and simultaneously decreasing the worsening of disability. Apart from its role as a second/third-line therapy, some studies suggest its use as an induction therapy. However, mitoxantrone use is limited because of its potential risk of severe adverse events, such as cardiotoxicity and the induction of therapy-related acute leukemia. Genetic markers are on evaluation to predict side effects and therapeutic efficacy, which is consistent with the direction of personalized treatment. Considering its efficacy and the potential risks, mitoxantrone use is limited to active patients after a careful, individualized evaluation of the risk/benefit balance.
Topics: Disability Evaluation; Humans; Immunosuppressive Agents; Mitoxantrone; Multiple Sclerosis; Treatment Outcome
PubMed: 24834466
DOI: 10.1586/14737175.2014.915742