Novantrone
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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 haematopoiesis, normal blood cell production. Sympt ...
. It improves the survival rate of children suffering from
acute lymphoblastic leukemia Acute lymphoblastic leukemia (ALL) is a cancer of the Lymphocyte, lymphoid line of blood cells characterized by the development of large numbers of lymphoblast, immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, ...
relapse. The combination of mitoxantrone and
prednisone Prednisone is a glucocorticoid medication mostly used to immunosuppressive drug, 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 ...
is approved as a second-line treatment for metastatic hormone-refractory
prostate cancer Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...
. This combination was once 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 sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...
(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. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...
,
vomiting Vomiting (also known as emesis, puking and throwing up) is the 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, pre ...
,
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 scarring ...
, 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 react ...
, possibly with delayed onset.
Cardiomyopathy Cardiomyopathy is a group of primary diseases of the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. A ...
is a particularly concerning effect as it is irreversible; thus regular monitoring with
echocardiogram Echocardiography, also known as cardiac ultrasound, is the use of ultrasound to examine the heart. It is a type of medical imaging, using standard ultrasound or Doppler ultrasound. The visual image formed using this technique is called an echo ...
s or
MUGA scan Radionuclide angiography is an area of nuclear medicine which specialises in imaging to show the functionality of the right and left ventricles of the heart, thus allowing informed diagnostic intervention in heart failure. It involves use of a ...
s 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 Inhibitor or inhibition may refer to: Biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotransmi ...
; 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 occu ...
and
DNA repair DNA repair is a collection of processes by which a cell (biology), cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is cons ...
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 ...
, a mitoxantrone analogue under development * Losoxantrone


References


External links

* {{Portal bar , Medicine Topoisomerase inhibitors IARC Group 2B carcinogens Hydroxyethyl compounds Drugs developed by Merck Aromatic amines Dihydroxyanthraquinones Hydroquinones DNA intercalaters 3-Hydroxypropenals within hydroxyquinones