Mitoxantrone: bluebeard for malignancies.
Mitoxantrone, an anthracenedione derivative, has been used for preclinical and clinical studies from the end of the 1970s. Several working mechanisms are suggested such as intercalation and electrostatic interactions with DNA with or without involvement of topoisomerase II, immunosuppressive effects and inhibition of prostacyclin synthesis. Efficacy of mitoxantrone alone or in combination with other chemotherapeutic drugs has been especially demonstrated in patients with breast cancer, leukemia and lymphoma. Locoregional (but not intrathecal) therapy with this drug is possible because it is not a vesicant. It has an improved tolerability profile compared with doxorubicin. Dose-limiting toxicity is myelotoxicity and mucositis. Therefore this drug has recently also been used in high doses with bone marrow support and in combination with hematopoietic growth factors. Cardiotoxicity is less frequent than after doxorubicin and daunorubicin. However, cardiac function tests are warranted after cumulative doses greater than 160 mg/m2 or earlier if additional risk factors, namely previous mediastinal irradiation, anthracycline therapy or cardiovascular disease, are present.
van der Graaf
W T
WT
Department of Internal Medicine, University Hospital, Groningen, The Netherlands.
de Vries
E G
EG
D000818:Animals; D006801:Humans; D015201:Meta-Analysis as Topic; D008942:Mitoxantrone / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
D008942:Mitoxantrone