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Novantrone

Novantrone I'm keen not to overstate the case on Novantrone. It works, and for people with agressive MS, it is often the best drug currently available. However, for people with mild or early RRMS, it's probably not the drug of choice. Each person should weigh up these decisions for themselves armed with all the facts and their doctors advice. It's certainly not a cut-and-dried case although, like Julie, I am happy that it is working for you. However, just to get technical with you, Rob ...

Mitoxantrone (also known as dihydroxyanthracenedione) is a chemotherapeutical drug branded under the name Novantrone. Mitoxantrone is used in low-doses for multiple sclerosis and at much higher doses for several types of cancer.

Mitoxantrone is one of a group of chemicals called antineoplastics which act as DNA intercalators. This means that they inproduce breaks in the DNA during cell divisiion. They also inhibit the enzyme topoisomerase II (one of a class of biochemicals involved in the regulation of DNA coiling) which further inhibits cell division.

This means that, at a high dose, they prevent almost all cell division and that includes bacterial mitosis as well as that of the bodies own cells. So yes, they will probably reduce the population of mycoplasmas. Whether that has anything to do with MS is an open question, but there are probably better, less toxic ways to rid oneself of a bacterial infection than through chemotherapy.

Additionally, ridding oneself of a bacteria that promotes autoimmunity doesn't end the autoimmune process. Chlamydia is a good case in point. Part of the effects of sexually transmitted Chlamydia (different but similar to Chlamydia Pneumonia) is to produce an autoimmune response in the genitals and this response continues even after the Chlamydia has been completely removed from the body!

As I said before, in immunological terms mitoxantrone and other DNA intercalators stop T- and B-cell (lymphocyte) division. One of the first things that lymphocytes do when their receptors recognise their target antigen (e.g. a myelin protein) is to clone themselves. Some of these clones shed their receptors as antibodies (in the case of B-cells), others release pro-inflammatory messenger molecules (in the case of helper T-cells) and still others leave the site of inflammation and become memory cells to recognise that same antigen later on (one of the reasons that MS is a chronic disease). These effects will reduce or stop inflammation (depending on the dose) because T- and B-cells are crucial to it. What they will not do is prevent axonal degeneration because it is very clear that inflammation is the sole cause of this. In fact, and purely in hypothetical terms, they may make it worse since they prevent the bodies own stem cells from mitotic replication and this will include O2A oligodendrocyte precursor cells.

Mitoxantrone is a relatively non-toxic chemotherapy which is rather like saying that the rattle snake is a relatively non-poisonous snake - it's very poisonous but not as bad as the Taipan of Australia. One of the reasons that mitoxantrone is relatively non-toxic is because it produces a relatively small amount of free radicals and also because some of its effects are reversible. All chemotherapies work by interferring with mitosis at the DNA level. Some actually bind to the DNA itself. These means that they prevent all growth including liver regeneration, hair growth and sperm production.

Mitoxantrone is quite a simple organic molecule, those with a basic grounding in chemistry will understand this diagram of its structure:

Chemical diagram of mitoxantrone

In time, I believe that monoclonal antibodies or designer vaccines will replace chemotherapies. These have the potential to be far less toxic and to be much more precisely targetted - eliminating a specific cell type rather than shutting down all cell replication. For example, Campath-1H only attacks cells that express the CD52 leukocyte antigen - chiefly the inflammation causing leukocytes. Antegren is another powerful but specific anti-inflammatory which attacks cells expressing the alpha-4-beta 1 (VLA-4) and alpha-4-beta-7 integrins thus interferring with leukocytes crossing the blood-brain-barrier into the central nervous system.

http://www.albany.net/~tjc/mitoxantrone.html

Chemical Name: Mitoxantrone for injection concentrate (mye-toe-ZAN-trone)
Brand Name: Novantrone (U.S. and Canada)

Generic Available: No
 
 

Description: Novantrone belongs to the general group of medicines called antineoplastics. Prior to its approval for use in MS, it was used only to treat certain forms of cancer.  It acts in MS by suppressing the activity of T cells, B cells, and macrophages that are thought to lead the attack on the myelin sheath.
 
 

The use of Novantrone for the treatment of MS has been evaluated in a series of European studies over a period of ten years.  In a recent randomized, placebo-controlled, multi-center clinical trial involving patients with secondary-progressive or progressive-relapsing disease, participants received 12mg/m2 of Novantrone by short IV infusion once every three months for 24 months.  Novantrone was found to delay the time to first treated relapse and time to disability progression.  It also reduced the number of treated relapses and number of new lesions detected by magnetic resonance imaging.
 
 

Based on findings from these studies, the FDA approved Novantrone in October, 2000 for reducing neurologic disability and/or the frequency of clinical relapses (attacks) in:

1.                  patients with secondary progressive MS (disease that has changed from relapsing-remitting to progressive at a variable rate)

2.                  progressive-relapsing MS (disease characterized by gradual increase in disability from onset with clear, acute relapses along the way);

3.                  worsening relapsing-remitting MS (disease characterized by clinical attacks without complete remission, resulting in a step-wise worsening of disability.

Novantrone has not been approved for the treatment of primary-progressive MS (characterized by progression from disease onset with no acute attacks or remissions).
 
 

Proper Usage
·        Evaluation of cardiac output is necessary before treatment is started.  The drug should be used only in those with normal cardiac function, once every three months at a dose of 12mg/m2.  Periodic cardiac monitoring is required throughout the treatment period.·

·        The lifetime cumulative dose is limited to 140 mg/m2 (approximately 8-12 doses over two to three years) because of possible cardiac toxicity.·

·        Because Novantrone can increase the risk for infection by decreasing the number of protective white blood cells, blood counts and liver function should be evaluated prior to each dose.
 
 

Precautions·

·        It is important that your doctor check your progress at regular intervals to make sure that this medicine is working properly and to check for unwanted effects.·

·        While being treated with this medication, and during the period following treatment, do not have any immunizations (vaccinations ) with live virus vaccines without your doctor’s approval.  Mitoxantrone may lower your body’s resistance to infection, making you susceptible to the infection that the immunization is designed to help you avoid.  Neither you nor anyone in your household should take the oral polio vaccine. ·

·        If possible, avoid people with infections.  Contact your physician if you think you are getting an infection, or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.·

·        When receiving Novantrone, it is important for your physician to know if you are taking any of the following:

o       Amphotericin B by injection

o       Antithyroid agents

o       Azathioprine

o       Chloramphenicol

o       Colchicine

o       Flucytosine

o       Ganciclovir

o       Plicamycin

o      Probenecid

o       Sulfinpyrazone

o       Zidovudine

or if you have previously been treated with:

o       radiation

o       other cancer medications·

·        The presence of other medical problems may affect the use of Novantrone.  Let your doctor know if you have any of the following:

o       chicken pox or recent exposure to it-

o       herpes zoster (shingles)

o       gout or history of gout

o       kidney stones

o       heart disease

o       liver disease·

·        The fluid for infusion is dark blue and may cause your urine to become blue-green in color for a period of 24 hours after each administration.  The whites of the eyes may also appear bluish in color.

·        Tell your doctor if you are pregnant or intending to have children.  This medicine may cause birth defects if either the man or woman is receiving it at the time of conception.  A pregnancy test is recommended prior to each treatment for women of child-bearing age.  Many medications of this type can cause permanent sterility.  Be sure you have discussed this with your physician before taking this medication.·

·        Novantrone is excreted in human milk.  Breast-feeding should be discontinued before a woman starts treatment.·

·        A higher incidence of leukemia has been reported in cancer patients, previously treated with chemotherapy, who were then treated with higher doses of Novantrone than is prescribed for treating MS.
 
 

Possible Side Effects·

·        Side effects that may go away as your body adjusts to the medication and do not require medical attention unless they continue or are bothersome: nausea, temporary hair loss, and menstrual disorders in females.

·        Side effects that should be reported to your physician as soon as possible: fever or chills, lower back or side pain; painful or difficult urination; swelling of feet and lower legs; black, tarry stools, cough or shortness of breath; sores in mouth and on lips, stomach pain.
 

Mitoxantrone links:
Medications Used in MS
Mitoxantrone
Other Anthrcycline Derivatives
ANTHRACENEDIONES (Mitoxantrone)


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