Evaluation of mitoxantrone for the treatment of multiple sclerosis.
Mitoxantrone (Novantrone((R))), an antineoplastic agent, has been approved for treating patients with secondary progressive multiple sclerosis (MS). Mitoxantrone, which is usually categorised as an immunosuppressant drug, is now also considered to be a specific immunomodulator. Autoimmune mechanism of pathogenesis of MS is the basis of immunosuppressive therapeutic approaches to MS whereas immunoregulatory abnormalities including defective IFN-alpha production provide the rationale for immunomodulating therapies. Clinical trials have shown that mitoxantrone had a statistically significant impact on reduction of relapse rate and delay in disability progression in these patients. Advantages of mitoxantrone as therapy for MS are: (1) considerable information is available about its pharmacokinetics, metabolism and toxicology from previous use in oncology; (2) it requires administration only once in three months which is not only convenient for the patient but also cost-effective; (3) mitoxantrone is one of the two drugs to be approved for secondary progressive MS (the other is IFN-beta1) which offers an advantage over IFN-beta1a preparations and glatiramer acetate which are indicated only for relapsing remitting MS. However, the duration of therapy is usually limited to two to three years because the maximum cumulative dose recommended is 120 mg/m(2) due to concern for possible cardiotoxicity. Potential market value of the mitoxantrone, based on the cost of treatment per patient and the number of patients likely to be treated in the first year of introduction, is US$210 million.
Jain
K K
KK
Jain PharmaBiotech, Bläsiring 7, CH-4057 Basel, Switzerland. jain@pharmabiotech.ch
D000818:Animals; D005260:Female; D006801:Humans; D008942:Mitoxantrone / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy* / Q000503:physiopathology; D011247:Pregnancy
D008942:Mitoxantrone