Mitoxantrone

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 Number	65271-80-9 Y
ATC code	L01DB07 (WHO)
PubChem	CID: 4212
IUPHAR/BPS	7242
DrugBank	DB01204 Y
ChemSpider	4067 Y
UNII	BZ114NVM5P Y
KEGG	D08224 Y
ChEBI	CHEBI:50729 Y
ChEMBL	CHEMBL58 Y
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 Y Key:KKZJGLLVHKMTCM-UHFFFAOYSA-N Y
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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.

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.

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.

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.

Mechanism of action

Human topoisomerase iibeta in complex with DNA and mitoxantrone. PDB entry 4g0v. 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 between the DNA bases.

See also

• Pixantrone, a mitoxantrone analogue under development
• Losoxantrone