Approval of Mitoxantrone by FDA

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The literal meaning of the term “chemotherapy” is “to treat with a chemical agent,” but the term generally refers to the use of potent cytotoxic (cell-killing) agents that are prescribed for some forms of cancer. These drugs not only kill tumor cells, but can destroy normal cells as well.
The cells that are most vulnerable to cytotoxic agents are those that grow and divide rapidly. Among those affected are cancer cells, hair and intestinal cells, red blood cells, and the white blood cells comprising the immune system.
The rationale for the use of chemotherapy to treat MS stems from the fact that MS is considered to be an autoimmune disease. An abnormal, heightened immune action of certain white blood cells mounts an attack on the myelin of the central nervous system. Destruction of myelin¾the fatty sheath that surrounds and insulates nerves¾causes nerve impulses to be slowed or halted and produces the symptoms of MS. Since administering chemotherapeutic agents diminishes the numbers of white blood cells, it should theoretically slow down or halt this autoimmune destruction.

Approval of Mitoxantrone (Novantrone®) by the FDA

On October 13, 2000, following a multi-center, randomized, placebo-controlled clinical trial, the FDA approved the marketing of mitoxantrone (Novantroneâ) for “reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary-progressive, progressive-relapsing or worsening relapsing-remitting MS.” In addition to being the first drug approved in the U.S. for secondary-progressive MS it offered new treatment options for others experiencing worsening of the disease.

Safety and Side Effects

The short-term safety and tolerability of mitoxantrone were found to be acceptable in the initial trials. Among the more common side effects seen were nausea, hair loss, urinary and upper respiratory tract infections, and menstrual disorders. The longer-term safety of Novantroneâ in MS is more problematic. Dose-related cardiac toxicity has been reported, primarily in cancer patients. Although no clinically significant cardiac problems were seen in the relatively short MS trials, the FDA recommended that Novantroneâ be used only by those with normal cardiac function, and for no more than a total cumulative dose of 140mg/m2 (once every three months at a dose of 12 mg/m2) because of possible cumulative cardiac toxicity.
In May, 2005, the FDA added a “black box warning” to the labeling of Novantrone®. Post-marketing reports of adverse events have shown that impaired cardiac function can occur at any time, even early in the treatment. The risk of cardiotoxicity increases with each dose of medication, and congestive heart failure can occur during or after treatment. To address this cardiac risk, the FDA now recommends cardiac monitoring—beginning with a cardiac evaluation prior to the start of treatment and again before each subsequent dose.
In addition to cardiac toxicity, acute myelogenous leukemia (AML), a type of cancer, has been reported in MS patients and cancer patients treated with Novantrone.