Mitoxantrone

Abstract

Acute nonlymphoblastic leukaemia (ANLL) is a malignant condition strongly associated with advancing age. Of adult acute leukaemias, 80 to 85% are classified as ANLL, with more than half of all patients being aged over 60 years. Although advancing age has been reported to be a poor prognostic factor in ANLL, recent clinical trials have shown good results in patients aged 60 years and over after coadministration of the anthracenedione antineoplastic agent mitoxantrone with cytarabine. In 1 study in particular, which involved patients aged 60 to 81 years, no correlation was found between increasing age and response rate. However results of a major clinical trial showed age greater than 60 years to be associated with poorer outcomes. Mitoxantrone as initial induction treatment is at least as effective as daunorubicin when either drug is given in combination with cytarabine to patients with previously untreated ANLL. Complete response rates in randomised comparative trials were 53 to 67% after mitoxantrone with cytarabine and 37 to 70% after daunorubicin with cytarabine. In a major US study, significantly more patients achieved a complete response after 1 treatment cycle of mitoxantrone and cytarabine than after daunorubicin and cytarabine. Mitoxantrone has also been effective in inducing complete remissions in patients with relapsed or refractory ANLL, mainly in combination with other antineoplastic agents. Overall survival appears similar after treatment with regimens containing either mitoxantrone or daunorubicin in patients with ANLL, although there have been reports of trends towards increased survival rates with mitoxantrone. The incidence of cardiotoxicity appears low in patients with ANLL who have received mitoxantrone. Lower cardiotoxicity of mitoxantrone relative to daunorubicin has not been conclusively demonstrated in patients with ANLL, although trials in patients with breast cancer have shown mitoxantrone to cause fewer cardiac adverse effects than doxorubicin. This is of particular interest in the elderly, as this group of patients is especially susceptible to the effects of anthracycline-induced cardiac toxicity. Thus, mitoxantrone is a suitable first-line agent for the induction of remission in patients with ANLL, with clearly demonstrated efficacy in patients aged 60 years and over.

Cancer immunotherapy via combining oncolytic virotherapy with chemotherapy: recent advances

“…Mitoxantrone (MTX) is a synthetic anthracenedione antineoplastic agent derived from the anthraquinone dye ametantrone,158 which is frequently used to manage prostate, leukemia, and breast cancer 159,160. It is structurally similar to Dox, with both drugs having a planar aromatic ring structure that enables them to interact with DNA by intercalation between base pairs.…”

Design, synthesis, and antiproliferative activity of some novel aminosubstituted xanthenones, able to overcome multidrug resistance toward MES-SA/Dx5 cells

“…1). 2,3 Numerous analogues of this agent are studied to eliminate its side effects, mainly cardiotoxicity 4 and the development of multidrug resistance (MDR). 5 Cumulative cardiotoxicity has limited the prolonged use of quinone derivatives and led to the development of anthrapyrazoles, 6 which due to the presence of a quasi-iminoquinone group, possess reduced cardiotoxicity.…”

A New Method for the Preparation of Intermediates for 2,6‐Substituted Anthrapyridazones

“…However, the attempts to directly transfer the published reaction conditions to the alkylation of 3 by 2-(dimethylamino)ethyl chloride hydrochloride (4a) failed. Initial experiments were performed in DMF or toluene in the presence of NaH, KOH, or NaOH ( 16,17), only traces of the product were observed. During our systematic modifications of reaction conditions, followed by the examination of the substrate conversion and the purity of the alkylation processes, it was revealed that chloroform may be the most promising medium for this type of reaction (Table 2; entry 18).…”