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Mitoxantrone (INN, BAN, USAN; also known as Mitozantrone in Australia; trade name Novantrone) is an anthracenedione antineoplastic agent.

Uses

Mitoxantrone is used in the treatment of certain types of cancer, mostly metastatic breast cancer, acute myeloid leukemia, and non-Hodgkin's lymphoma. It was also shown to improve the survival rate of children suffering from first relapse of acute lymphoblastic leukemia.^[1]

The combination of mitoxantrone and prednisone is approved as a second-line treatment for metastatic hormone-refractory prostate cancer. Until recently this combination has been the first line of treatment; however, a combination of docetaxel and prednisone has been shown to improve survival rates and lengthen the disease-free period.^[2]

Mitoxantrone is also used to treat multiple sclerosis (MS), most notably the subset of the disease, known as secondary-progressive MS. As no cure for multiple sclerosis exists yet, it must be understood mitoxantrone will not cure the disease, but rather 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.^[3]

Side effects

Mitoxantrone, as other drugs in its class, may cause several adverse reactions of varying severity, such as nausea, vomiting, hair loss, heart damage, and immunosuppression, which may also have a delayed onset. Cardiomyopathy is a particularly concerning effect as it is irreversible; thus regular monitoring with echocardiograms or MUGA scans is recommended for people taking mitoxantrone.

Because of the risk of cardiomyopathy, mitoxantrone carries a limit on the cumulative lifetime dose (based on body surface area) in patients with multiple sclerosis.^[4]

Mechanism of action

Human topoisomerase iibeta in complex with DNA and mitoxantrone. PDB entry 4g0v.^[5] Detail showing mitoxantrone (spheres) intercalated with DNA.

Mitoxantrone is a type II topoisomerase inhibitor; it disrupts DNA synthesis and DNA repair in both healthy cells and cancer cells, by intercalation^[6] between the DNA bases.

References

^ 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 (2010). "Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial". Lancet 376 (9757): 2009–2017. doi:10.1016/S0140-6736(10)62002-8. PMC 3010035. PMID 21131038.
^ Katzung, Bertram G. (2006). "Cancer Chemotherapy". Basic and clinical pharmacology (10th ed.). New York: McGraw-Hill Medical Publishing Division. ISBN 0-07-145153-6. OCLC 157011367.
^ Fox E (2006). "Management of worsening multiple sclerosis with mitoxantrone: a review". Clin Ther 28 (4): 461–74. doi:10.1016/j.clinthera.2006.04.013. PMID 16750460.
^ "Mitoxantrone Hydrochloride (marketed as Novantrone and generics) - Healthcare Professional Sheet text version". U.S. Food and Drug Administration. Retrieved 19 September 2014.
^ Wu, C. -C.; Li, Y. -C.; Wang, Y. -R.; Li, T. -K.; Chan, N. -L. (2013). "On the structural basis and design guidelines for type II topoisomerase-targeting anticancer drugs". Nucleic Acids Research 41 (22): 10630–10640. doi:10.1093/nar/gkt828. PMID 24038465. edit
^ Mazerski J, Martelli S, Borowski E (1998). "The geometry of intercalation complex of antitumor mitoxantrone and ametantrone with DNA: molecular dynamics simulations". Acta Biochim. Pol. 45 (1): 1–11. PMID 9701490.
^ Baron M, Giorgi-Renault S, Renault J et al. (1984). "Heterocycles with a quinone function.5.An abnormal reaction of butanedione with 1,2-diaminoanthraquinone - Crystalline structure obtained from naphto(2,3-f) quinoxaline-7,12 dione". Can. J. Chem. (in French) 62 (3): 526–530. doi:10.1139/v84-087.

UpToDate Contents

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1. アントラサイクリン系薬剤による心毒性の予防とマネージメント prevention and management of anthracycline cardiotoxicity
2. 去勢抵抗性前立腺癌（CRPC）の治療法の概要 overview of the treatment of castration resistant prostate cancer crpc
3. 去勢抵抗性前立腺癌への化学療法 chemotherapy in castration resistant prostate cancer
4. 成人における進行性多発性硬化症の治療 treatment of progressive multiple sclerosis in adults
5. 成人の再発寛解型多発性硬化症への疾患修飾療法 disease modifying treatment of relapsing remitting multiple sclerosis in adults

English Journal

Cationic drug-based self-assembled polyelectrolyte complex micelles: Physicochemical, pharmacokinetic, and anticancer activity analysis.

Ramasamy T1, Poudel BK1, Ruttala H1, Choi JY1, Hieu TD1, Umadevi K2, Youn YS3, Choi HG4, Yong CS5, Kim JO6.
Colloids and surfaces. B, Biointerfaces.Colloids Surf B Biointerfaces.2016 Oct 1;146:152-60. doi: 10.1016/j.colsurfb.2016.06.004. Epub 2016 Jun 5.
Nanofabrication of polymeric micelles through self-assembly of an ionic block copolymer and oppositely charged small molecules has recently emerged as a promising method of formulating delivery systems. The present study therefore aimed to investigate the interaction of cationic drugs doxorubicin (D
PMID 27318960

Activity of ABCG2 Is Regulated by Its Expression and Localization in DHT and Cyclopamine-Treated Breast Cancer Cells.

Chua VY1,2, Larma I3, Harvey J2, Thomas MA1, Bentel JM1.
Journal of cellular biochemistry.J Cell Biochem.2016 Oct;117(10):2249-59. doi: 10.1002/jcb.25523. Epub 2016 Apr 7.
Elevated expression of the efflux transporter, ATP-binding cassette subfamily G isoform 2 (ABCG2) on the plasma membrane of cancer cells contributes to the development of drug resistance and is a key characteristic of cancer stem cells. In this study, gene expression analysis identified that treatme
PMID 26917208

Consolidation therapy with mitoxantrone, ifosfamide and etoposide with or without rituximab before stem cell transplantation in relapsed diffuse large B-cell lymphoma patients failing second-line treatment.

Amorim S1,2, Fleury I1, Mounier N3, Harel S1,2, Brice P1, Thieblemont C1,2.
Leukemia & lymphoma.Leuk Lymphoma.2016 Oct;57(10):2425-8. doi: 10.3109/10428194.2015.1135437. Epub 2016 Jan 11.
PMID 26750643

Japanese Journal

肝生検が診断に有用であった血管内リンパ腫の2例

星智子,藤井善憲,奥山俊介,田中裕一,木村昇,毛利陽一,髙谷晴夫,梶村幸三
日本消化機病學會雜誌. 乙 111(7), 1433-1440, 2014
38℃台の発熱と肝胆道系酵素の上昇を主訴に紹介され，肝生検から診断に至った血管内リンパ腫（intravascular lymphoma；IVL）の2症例を報告する．症例1は診断に至ったものの化学療法が間に合わず救命できなかったが，症例2は早期診断から早期に化学療法を施行できたため寛解導入に成功した．IVLの早期診断法として肝生検は有用な方法の1つと考える．
NAID 130004776852

濾胞性リンパ腫に対するRFM療法後に発症した治療関連慢性骨髄性白血病

柴崎美緒,住昌彦,武田航 [他],桐原健彦,栗原太郎,佐藤慶二郎,植木俊充,廣島由紀,上野真由美,市川直明,森勇一,小林光
臨床血液 55(8), 970-974, 2014
症例は61歳女性。52歳時に右乳癌に対し乳房温存術・放射線療法の既往あり。2007年に濾胞性リンパ腫を発症しRFM療法（リツキシマブ，フルダラビン，ミトキサントロン）で完全寛解となり経過観察中，2010年に慢性期慢性骨髄性白血病(CML-CP)を発症した。イマチニブで細胞遺伝学的完全寛解(CCyR)となったが，2013年1月に末梢血でリンパ芽球を65%認めリンパ芽球性急性転化と診断，染色体検査でフ …
NAID 130004688012

Asterosaponins from the Starfish Astropecten monacanthus Suppress Growth and Induce Apoptosis in HL-60, PC-3, and SNU-C5 Human Cancer Cell Lines

, , , , , , , , ,
Biological and Pharmaceutical Bulletin 37(2), 315-321, 2014
… Relative to the effects of the postitive control mitoxantrone, the MeOH extract (with IC50 values ranging from 0.84±0.03 to 3.96±0.14 µg/mL) and astrosterioside D (5) (with IC50 values ranging from 4.31±0.07 to 5.21±0.15 µ<span style="font-variant: small-caps;">M</span>) exhibited potent cytotoxic effects against all three tested human cancer cell lines. …
NAID 130003390928

Related Pictures

★リンクテーブル★

リンク元	「ミトキサントロン」「novantrone」
拡張検索	「mitoxantrone hydrochloride」

「ミトキサントロン」

Mitoxantrone
Systematic (IUPAC) name
	1,4-dihydroxy-5,8-bis[2-(2-hydroxyethylamino); ethylamino]-anthracene-9,10-dione
Clinical data
Trade names	Novantrone
AHFS/Drugs.com	monograph
MedlinePlus	a608019
Pregnancy; category	US: D (Evidence of risk);
Legal status	℞ (Prescription only);
Routes of; administration	Mainly intravenous
Pharmacokinetic data
Bioavailability	n/a
Protein binding	78%
Metabolism	Hepatic (CYP2E1)
Biological half-life	75 hours
Excretion	Renal
Identifiers
CAS Registry Number	65271-80-9
ATC code	L01DB07
PubChem	CID: 4212
IUPHAR/BPS	7242
DrugBank	DB01204
ChemSpider	4067
UNII	BZ114NVM5P
KEGG	D08224
ChEBI	CHEBI:50729
ChEMBL	CHEMBL58
PDB ligand ID	MIX (PDBe, RCSB PDB)
Chemical data
Formula	C22H28N4O6
Molecular mass	444.481 g/mol
	SMILES O=C2c1c(c(NCCNCCO)ccc1NCCNCCO)C(=O)c3c2c(O)ccc3O ;
	InChI InChI=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 ; Key:KKZJGLLVHKMTCM-UHFFFAOYSA-N ;
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