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

Mitoxantrone
Mitoxantrone skeletal.svg
Mitoxantrone ball-and-stick.png
Clinical data
Trade namesNovantrone
AHFS/Drugs.comMonograph
MedlinePlusa608019
Pregnancy
category
  • US: D (Evidence of risk)
Routes of
administration
Mainly intravenous
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailabilityn/a
Protein binding78%
MetabolismHepatic (CYP2E1)
Elimination half-life75 hours
ExcretionRenal
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC22H28N4O6
Molar mass444.481 g/mol g·mol−1
3D model (JSmol)
  (verify)

UsesEdit

Mitoxantrone is used to treat certain types of cancer, mostly metastatic breast cancer, acute myeloid leukemia, and non-Hodgkin's lymphoma. It improves the survival rate of children suffering from acute lymphoblastic leukemia relapse.[1]

The combination of mitoxantrone and prednisone is approved as a second-line treatment for metastatic hormone-refractory prostate cancer. Until recently this combination was the first line of treatment; however, a combination of docetaxel and prednisone improves survival rates and lengthens 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. 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.[3]

Side effectsEdit

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.[4]

Mechanism of actionEdit

 
Human topoisomerase II beta 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][7] between DNA bases. It is also classified as an antibiotic.[8]

See alsoEdit

ReferencesEdit

  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.
  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.
  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. PMC 3905874. PMID 24038465.
  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.
  7. ^ Kapuscinski J, Darzynkiewicz Z. (1985) Interactions of antitumor agents Ametantrone and Mitoxantrone (Novatrone) with double-stranded DNA.Biochem Pharmacol. 1985;34:4203-13, PMID 4074383
  8. ^ "Mitoxantrone".