Mitoxantrone is an anthracenedione (not an anthracycline) antineoplastic agent.

Uses

It is used in the treatment of certain types of cancer, mostly metastatic

Metastasis

Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

 breast cancer

Breast cancer

Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

, acute myeloid leukemia

Acute myeloid leukemia

Acute myeloid leukemia , also known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute...

, and non-Hodgkin's lymphoma. It was also shown to improve the survival of children suffering from first relapse of acute lymphoblastic leukaemia.

The combination of mitoxantrone and prednisone

Prednisone

Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...

 is approved as a second-line treatment for metastatic hormone-refractory prostate cancer

Prostate cancer

Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...

. This combination has been the first line of treatment, until recently, when combination of docetaxel and prednisone has been shown to improve survival and disease-free period.
Mitoxantrone is also used to treat multiple sclerosis

Multiple sclerosis

Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...

 (MS), most notably the subset known as secondary progressive MS. Mitoxantrone will not cure multiple sclerosis, but is effective in slowing the progression of secondary progressive MS and extending the time between relapses in relapsing-remitting MS and progressive relapsing MS.

Mechanism of action

Mitoxantrone is a type II topoisomerase

Type II topoisomerase

Type II topoisomerases cut both strands of the DNA helix simultaneously in order to manage DNA tangles and supercoils. They use the hydrolysis of ATP, unlike type I topoisomerase. In this process, these enzymes change the linking number of circular DNA by +/-2....

 inhibitor

Topoisomerase inhibitor

Topoisomerase inhibitors are agents designed to interfere with the action of topoisomerase enzymes , which are enzymes that control the changes in DNA structure by catalyzing the breaking and rejoining of the phosphodiester backbone of DNA strands during the normal cell cycle.In recent years,...

; it disrupts DNA synthesis

DNA synthesis

DNA synthesis commonly refers to:*DNA replication - DNA biosynthesis *Polymerase chain reaction - enzymatic DNA synthesis *Oligonucleotide synthesis - chemical synthesis of nucleic acids...

 and DNA repair

DNA repair

DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...

 in both healthy cells and cancer cells.

It also engages in intercalation

Intercalation (chemistry)

In chemistry, intercalation is the reversible inclusion of a molecule between two other molecules . Examples include DNA intercalation and graphite intercalation compounds.- DNA intercalation :...

.

Side effects

As other drugs in its class, mitoxantrone may cause several adverse reaction

Adverse drug reaction

An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...

s of varying severity, such as nausea

Nausea

Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

, vomiting

Vomiting

Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...

, hair loss, heart damage, and immunosuppression

Immunosuppression

Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...

. Some side effects may have delayed onset. Cardiomyopathy

Cardiomyopathy

Cardiomyopathy, which literally means "heart muscle disease," is the deterioration of the function of the myocardium for any reason. People with cardiomyopathy are often at risk of arrhythmia or sudden cardiac death or both. Cardiomyopathy can often go undetected, making it especially dangerous to...

 is a particularly concerning effect as it is irreversible; regular monitoring with echocardiograms or MUGA scan

MUGA scan

A MUGA scan is a time-proven yet dated nuclear medicine test designed to evaluate the function of the right and left ventricles of the heart, thus allowing informed diagnostic intervention in heart failure. It is also called radionuclide angiography, as well as gated blood pool imaging...

s is recommended for people taking mitoxantrone.

The medication carries a total lifetime dose based on body surface area.

Synthesis

See also

• Pixantrone
  Pixantrone
  Pixantrone is an experimental antineoplastic drug, an analogue of mitoxantrone with fewer toxic effects on cardiac tissue. It acts as a topoisomerase II poison and intercalating agent...
  
  , a mitoxantrone analogue
  Analog (chemistry)
  In chemistry, a structural analog , also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced...
  
   under development
• Naphtoquinoxalinediones, potential antitumorals, obtained from diamino-1,2 anthraquinones using a regioselective synthesis.
• ametantrone
• piroxantrone