塩酸ミトキサントロン

関: mitoxantrone

WordNet

a complex consisting of an organic base in association with hydrogen chloride

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/10/12 18:24:27」(JST)

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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.
^ 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.

UpToDate Contents

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1. 播種性前立腺癌に対する治療の概要 overview of the treatment of disseminated prostate cancer
2. Chemotherapy in castration-resistant prostate cancer
3. 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
4. 再発性または難治性の濾胞性リンパ腫の治療 treatment of relapsed or refractory follicular lymphoma
5. アントラサイクリン系化学療法剤の心毒性 cardiotoxicity of anthracycline like chemotherapy agents

English Journal

Epidermal growth factor receptor (EGFR) inhibitor PD153035 reverses ABCG2-mediated multidrug resistance in non-small cell lung cancer: In vitro and in vivo.

Zhang GN1, Zhang YK1, Wang YJ1, Gupta P1, Ashby CR Jr.2, Alqahtani S3, Deng T1, Bates SE4, Kaddoumi A3, Wurpel JND1, Lei YX5, Chen ZS6.
Cancer letters.Cancer Lett.2018 Jun 28;424:19-29. doi: 10.1016/j.canlet.2018.02.040. Epub 2018 Mar 5.
PMID 29518481

Long-term efficacy and toxicity of rituximab plus fludarabine and mitoxantrone (R-FM) for gastric marginal zone lymphoma: a single-center experience and literature review.

Cencini E1,2, Fabbri A3, Lauria F4, Bocchia M3,4.
Annals of hematology.Ann Hematol.2018 May;97(5):821-829. doi: 10.1007/s00277-018-3243-7. Epub 2018 Jan 16.
PMID 29340761

Hyaluronic acid/polyethylene glycol nanoparticles for controlled delivery of mitoxantrone.

Sargazi A1, Kamali N1,2, Shiri F3, Heidari Majd M1.
Artificial cells, nanomedicine, and biotechnology.Artif Cells Nanomed Biotechnol.2018 May;46(3):500-509. doi: 10.1080/21691401.2017.1324462. Epub 2017 May 14.
PMID 28503952

Japanese Journal

Ｐａｃｌｉｔａｘｅｌ，Ｍｉｔｏｘａｎｔｒｏｎｅ，ＩＦＮ‐α，Ｃｅｐｈａｒａｎｔｈｉｎの併用による進行期悪性黒色腫に対する治療の試み

安西三郎,内林義知,佐藤俊宏,寺師浩人,高安進,藤原作平,在永光行,中城正夫,三浦隆,山口都美子
西日本皮膚科 64(4), 483-486, 2002
… cepharanthin, interferon-<I>α</I>(IFN-<I>α</I>), paclitaxel, mitoxantroneの4剤を投与したところ転移巣は全て消退した。 …
NAID 130004474817

5'-Deoxy-5-Fluorouridine, Medroxyprogestrone Acetate and Mitoxantrone Hydrochloride for Advanced or Recurrent Breast Cancer

SATA Kazuhiko,HIRAIDE Hoshio,TAMAKUMA Shoetsu,TABEI Toshio,MARUYAMA Masashige,TOUMA Mituyuki,OKAMURA Haruaki,MATSUMOTO Fumio,AKAO Shuichi,ISHIKAWA Hiroshi,YAGI Yoshihiro,MOCHIZUKI Hidetaka
Breast cancer : the journal of the Japanese Breast Cancer Society 8(1), 58-62, 2001-01-25
NAID 10007066457

「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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　　[★]

英: mitoxantrone, MIT
化: 塩酸ミトキサントロン, mitoxantrone hydrochloride
商: ノバントロン, Novantrone

「hydrochloride」

　　[★] 塩酸塩、ハイドロクロライド　

[Parker-1] 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.

[2] 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-3] 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.

[FDA_Postmarket_Drug_Safety-4] "Mitoxantrone Hydrochloride (marketed as Novantrone and generics) - Healthcare Professional Sheet text version". U.S. Food and Drug Administration. Retrieved 19 September 2014.

[5] 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.

[pmid-6] 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.

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案内

案内

mitoxantrone hydrochloride