Mitoxantrone

Uses

Mitoxantrone is used to treat certain types of cancer, mostly acute myeloid leukemia. It improves the survival rate of children suffering from acute lymphoblastic leukemia relapse.

The combination of mitoxantrone and prednisone is approved as a second-line treatment for metastatic hormone-refractory prostate cancer. This combination was once the first line of treatment; however, a combination of docetaxel and prednisone improves survival rates and lengthens the disease-free period.

Mitoxantrone is also used to treat multiple sclerosis (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, vomiting, hair loss, heart damage and immunosuppression, possibly with delayed onset. Cardiomyopathy is a particularly concerning effect as it is irreversible; thus regular monitoring with echocardiograms 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 inhibitor; it disrupts DNA synthesis and DNA repair in both healthy cells and cancer cells by intercalation between DNA bases. It is also classified as an antibiotic.

References

References

1. (December 2010). "Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial". Lancet.
2. (2006). "Basic and clinical pharmacology". McGraw-Hill Medical Publishing Division.
3. (April 2006). "Management of worsening multiple sclerosis with mitoxantrone: a review". Clinical Therapeutics.
4. "Mitoxantrone Hydrochloride (marketed as Novantrone and generics) – Healthcare Professional Sheet text version". U.S. Food and Drug Administration.
5. (1998). "The geometry of intercalation complex of antitumor mitoxantrone and ametantrone with DNA: molecular dynamics simulations". Acta Biochimica Polonica.
6. (December 1985). "Interactions of antitumor agents Ametantrone and Mitoxantrone (Novatrone) with double-stranded DNA". Biochemical Pharmacology.
7. "Mitoxantrone".
8. (December 2013). "On the structural basis and design guidelines for type II topoisomerase-targeting anticancer drugs". Nucleic Acids Research.