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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 to treat certain types of cancer, mostly
acute myeloid leukemia Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may include ...
. It improves the survival rate of children suffering from acute lymphoblastic leukemia relapse. The combination of mitoxantrone and
prednisone Prednisone is a glucocorticoid medication mostly used to suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium due to cancer and adre ...
is approved as a second-line treatment for metastatic hormone-refractory
prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...
. Until recently this combination was the first line of treatment; however, a combination of
docetaxel Docetaxel (DTX or DXL), sold under the brand name Taxotere among others, is a chemotherapy medication used to treat a number of types of cancer. This includes breast cancer, head and neck cancer, stomach cancer, prostate cancer and non-small-cel ...
and prednisone improves survival rates and lengthens the disease-free period. Mitoxantrone is also used to treat
multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This ...
(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.


Side effects

Mitoxantrone, as with other drugs in its class, may cause adverse reactions of varying severity, including
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
,
vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis ...
,
hair loss Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarri ...
, heart damage and
immunosuppression Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reacti ...
, possibly with delayed onset. Cardiomyopathy is a particularly concerning effect as it is irreversible; thus regular monitoring with
echocardiogram An echocardiography, echocardiogram, cardiac echo or simply an echo, is an ultrasound of the heart. It is a type of medical imaging of the heart, using standard ultrasound or Doppler ultrasound. Echocardiography has become routinely used in th ...
s 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.


Mechanism of action

Mitoxantrone is a
type II topoisomerase Type II topoisomerases are topoisomerases that 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 th ...
inhibitor; it disrupts
DNA synthesis DNA synthesis is the natural or artificial creation of deoxyribonucleic acid (DNA) molecules. DNA is a macromolecule made up of nucleotide units, which are linked by covalent bonds and hydrogen bonds, in a repeating structure. DNA synthesis occurs ...
and
DNA repair DNA repair is 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 radiation can cause DNA dama ...
in both healthy cells and cancer cells by intercalation between DNA bases. It is also classified as an antibiotic.


See also

*
Pixantrone Pixantrone ( rINN; trade name Pixuvri) is an experimental antineoplastic (anti-cancer) drug, an analogue of mitoxantrone with fewer toxic effects on cardiac tissue. It acts as a topoisomerase II poison and intercalating agent. The code name BBR ...
, a mitoxantrone analogue under development *
Losoxantrone Losoxantrone (biantrazole) is an anthroquinone anthrapyrazole antineoplastic agent and analog of mitoxantrone. It is also sometimes known as DuP 941. See also *Mitoxantrone Mitoxantrone (INN, BAN, USAN; also known as Mitozantrone in Austra ...


References


External links

* {{Portal bar , Medicine Topoisomerase inhibitors IARC Group 2B carcinogens Primary alcohols Merck brands Aromatic amines Dihydroxyanthraquinones Hydroquinones DNA intercalaters 3-Hydroxypropenals within hydroxyquinones