{{Short description|Chemical compound}} {{Drugbox | verifiedrevid = 462252883 | IUPAC_name = 1,4-dihydroxy-5,8-bis[2-(2-hydroxyethylamino)<br>ethylamino]-anthracene-9,10-dione | image = Mitoxantrone skeletal.svg | image_class = skin-invert-image | image2 = Mitoxantrone ball-and-stick.png | image_class2 = bg-transparent <!--Clinical data--> | tradename = Novantrone | Drugs.com = {{drugs.com|monograph|mitoxantrone-hydrochloride}} | MedlinePlus = a608019 | pregnancy_US = D | legal_status = Rx-only | routes_of_administration = Mainly intravenous <!--Pharmacokinetic data--> | bioavailability = n/a | protein_bound = 78% | metabolism = Hepatic (CYP2E1) | elimination_half-life = 75 hours | excretion = Renal <!--Identifiers--> | IUPHAR_ligand = 7242 | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 65271-80-9 | ATC_prefix = L01 | ATC_suffix = DB07 | PubChem = 4212 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB01204 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 4067 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = BZ114NVM5P | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D08224 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 50729 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 58 | PDB_ligand = MIX <!--Chemical data--> | C=22 | H=28 | N=4 | O=6 | SMILES = O=C2c1c(c(NCCNCCO)ccc1NCCNCCO)C(=O)c3c2c(O)ccc3O | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C22H28N4O6/c27-11-9-23-5-7-25-13-1-2-14(26-8-6-24-10-12-28)18-17(13)21(31)19-15(29)3-4-16(30)20(19)22(18)32/h1-4,23-30H,5-12H2 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = KKZJGLLVHKMTCM-UHFFFAOYSA-N }} '''Mitoxantrone''' (INN, BAN, USAN; also known as '''Mitozantrone''' in Australia; trade name '''Novantrone''') is an anthracenedione antineoplastic agent.
==Uses== Mitoxantrone is used to treat certain types of cancer, mostly acute myeloid leukemia. It improves the survival rate of children suffering from acute lymphoblastic leukemia relapse.<ref name="Parker">{{cite journal | vauthors = Parker C, Waters R, Leighton C, Hancock J, Sutton R, Moorman AV, Ancliff P, Morgan M, Masurekar A, Goulden N, Green N, Révész T, Darbyshire P, Love S, Saha V | display-authors = 6 | title = Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial | journal = Lancet | volume = 376 | issue = 9757 | pages = 2009–2017 | date = December 2010 | pmid = 21131038 | pmc = 3010035 | doi = 10.1016/S0140-6736(10)62002-8 }}</ref>
The combination of mitoxantrone and prednisone is approved as a second-line treatment for metastatic hormone-refractory prostate cancer. This combination was once the first line of treatment; however, a combination of docetaxel and prednisone improves survival rates and lengthens the disease-free period.<ref>{{cite book |chapter=Cancer Chemotherapy | vauthors = Katzung BG |title=Basic and clinical pharmacology |publisher=McGraw-Hill Medical Publishing Division |location=New York |year=2006 |isbn=0-07-145153-6 |edition=10th |oclc=157011367}}</ref> Mitoxantrone is also used to treat multiple sclerosis (MS), most notably the subset of the disease known as secondary-progressive MS. In the absence of a cure, mitoxantrone is effective in slowing the progression of secondary-progressive MS and extending the time between relapses in both relapsing-remitting MS and progressive-relapsing MS.<ref name="Fox">{{cite journal | vauthors = Fox EJ | title = Management of worsening multiple sclerosis with mitoxantrone: a review | journal = Clinical Therapeutics | volume = 28 | issue = 4 | pages = 461–474 | date = April 2006 | pmid = 16750460 | doi = 10.1016/j.clinthera.2006.04.013 }}</ref>
==Side effects== Mitoxantrone, as with other drugs in its class, may cause adverse reactions of varying severity, including nausea, vomiting, hair loss, heart damage and immunosuppression, possibly with delayed onset. Cardiomyopathy is a particularly concerning effect as it is irreversible; thus regular monitoring with echocardiograms or MUGA scans is recommended for patients.
Because of the risk of cardiomyopathy, mitoxantrone carries a limit on the cumulative lifetime dose (based on body surface area) in MS patients.<ref name="FDA Postmarket Drug Safety">{{cite web|title=Mitoxantrone Hydrochloride (marketed as Novantrone and generics) – Healthcare Professional Sheet text version|url=https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm126445.htm|archive-url=https://web.archive.org/web/20090603133845/http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm126445.htm|url-status=dead|archive-date=June 3, 2009|publisher=U.S. Food and Drug Administration|access-date=19 September 2014|ref=fdapostmarket}}</ref>
==Mechanism of action== Mitoxantrone is a type II topoisomerase inhibitor; it disrupts DNA synthesis and DNA repair in both healthy cells and cancer cells by intercalation<ref name="pmid">{{cite journal | vauthors = Mazerski J, Martelli S, Borowski E | title = The geometry of intercalation complex of antitumor mitoxantrone and ametantrone with DNA: molecular dynamics simulations | journal = Acta Biochimica Polonica | volume = 45 | issue = 1 | pages = 1–11 | year = 1998 | pmid = 9701490 | doi = 10.18388/abp.1998_4280 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Kapuscinski J, Darzynkiewicz Z | title = Interactions of antitumor agents Ametantrone and Mitoxantrone (Novatrone) with double-stranded DNA | journal = Biochemical Pharmacology | volume = 34 | issue = 24 | pages = 4203–4213 | date = December 1985 | pmid = 4074383 | doi = 10.1016/0006-2952(85)90275-8 }}</ref> between DNA bases. It is also classified as an antibiotic.<ref>{{Cite web | url=https://livertox.nlm.nih.gov/Mitoxantrone.htm | archive-url=https://web.archive.org/web/20150906072207/http://livertox.nlm.nih.gov/Mitoxantrone.htm | url-status=dead | archive-date=September 6, 2015 | title=Mitoxantrone}}</ref> thumb|left|Human topoisomerase II beta in complex with DNA and mitoxantrone. PDB entry {{PDBe|4g0v}}.<ref>{{cite journal | vauthors = Wu CC, Li YC, Wang YR, Li TK, Chan NL | title = On the structural basis and design guidelines for type II topoisomerase-targeting anticancer drugs | journal = Nucleic Acids Research | volume = 41 | issue = 22 | pages = 10630–10640 | date = December 2013 | pmid = 24038465 | pmc = 3905874 | doi = 10.1093/nar/gkt828 }}</ref> Detail showing mitoxantrone (spheres) intercalated with DNA.
== See also == * Pixantrone, a mitoxantrone analogue under development * Losoxantrone
== References == {{Reflist}}
== External links == * {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/mitoxantrone | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Mitoxantrone }}
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Category:Topoisomerase inhibitors Category:IARC Group 2B carcinogens Category:Hydroxyethyl compounds Category:Drugs developed by Merck Category:Aromatic amines Category:Dihydroxyanthraquinones Category:Hydroquinones Category:DNA intercalaters Category:3-Hydroxypropenals within hydroxyquinones