Mitoxantrone: a review of its pharmacological properties and use in acute nonlymphoblastic leukaemia

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.