Mitoxantrone

Abstract

Mitoxantrone is a dihydroxyanthracenedione derivative which as intravenous mono- and combination therapy has demonstrated therapeutic efficacy similar to that of standard induction and salvage treatment regimens in advanced breast cancer, non-Hodgkin's lymphoma, acute nonlymphoblastic leukaemia and chronic myelogenous leukaemia in blast crisis; it appears to be an effective alternative to the anthracycline component of standard treatment regimens in these indications. Mitoxantrone is also effective as a component of predominantly palliative treatment regimens for hepatic and advanced ovarian carcinoma. Limited studies suggest useful therapeutic activity in multiple myeloma and acute lymphoblastic leukaemia. Regional therapy of malignant effusions, hepatic and ovarian carcinomas has also been very effective, with a reduction in systemic adverse effects. Mitoxantrone inhibits DNA synthesis by intercalating DNA, inducing DNA strand breaks, and causing DNA aggregation and compaction, and delays cell cycle progression, particularly in late S phase. In vitro antitumour activity is concentration- and exposure time-proportional, and synergy with other antineoplastic drugs has been demonstrated in murine tumour models. Leucopenia may be dose-limiting in patients with solid tumours, whereas stomatitis may be dose-limiting in patients with leukaemia. Other adverse effects are usually of mild or moderate severity although cardiac effects, particularly congestive heart failure, may be of concern, especially in patients with a history of anthracycline therapy, mediastinal irradiation or cardiovascular disease. Mitoxantrone displays an improved tolerability profile compared with doxorubicin and other anthracyclines, although myelosuppression may occur more frequently. Thus, mitoxantrone is an effective and better tolerated alternative to the anthracyclines in most haematological malignancies, in breast cancer and in advanced hepatic or ovarian carcinoma. Further studies may consolidate its role in the treatment of these and other malignancies.

Effects of Mitoxantrone on Multiple Sclerosis Patients’ Lymphocyte Subpopulations and Production of Immunoglobulin, TNF-alpha and IL-10

“…It demonstrated therapeutic efficacy in the treatment of a wide range of solid tumours, such as breast cancer, and haematological malignancies [1]. Based on beneficial results from the experimental allergic encephalomyelitis (EAE) animal model of multiple sclerosis (MS), where mitoxantrone suppressed relapses and lesions 10–20 times more effectively than cyclophosphamide [5, 6, 7], pilot studies showed positive effects on relapse and progression rate in heterogeneous groups of patients who had an unfavourable course of disease not responsive to other established immunotherapies [9, 10].…”

Reversible and formaldehyde-mediated covalent binding of a bis-amino mitoxantrone analogue to DNA

“…9,10 However, it has also been proposed that anthracenedione drugs containing side chain amine groups can induce apoptosis in cancer cells through formation of a covalent adduct with the N-2 amino group of a guanine residue at CpG sites after activation by formaldehyde. [14][15][16] The results of this study confirm that daunorubicin, mitoxantrone and pixantrone can form covalent adducts with duplex DNA.…”

Investigation of the Interaction between Nitrite Ion and Bovine Serum Albumin Using Spectroscopic and Molecular Docking Techniques

“…In contrast, increasing temperature is likely to result in the decreased stability of the complex, and thus lowers the value of the static quenching constant. 34,35 In order to test this view, the fluorescence quenching data were analyzed by the well-known Stern-Volmer Eq. (1).…”