MITOXANTRONE - A REVIEW OF ITS PHARMACOLOGICAL PROPERTIES AND USE IN ACUTE NONLYMPHOBLASTIC LEUKEMIA

Acute nonlymphoblastic leukaemia (ANLL) is a malignant condition stron gly associated with advancing age. Of adult acute leukaemias, 80 to 85 % are classified as ANLL, with more than half of all patients being ag ed over 60 years. Although advancing age has been reported to be a poo r prognostic factor in ANLL, recent clinical trials have shown good re sults 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, n o correlation was found between increasing age and response I-ate. How ever results of a major clinical trial showed age greater than 60 year s to be associated with poorer outcomes. Mitoxantrone as initial induc tion treatment is at least as effective as daunorubicin when either dr ug is given in combination with cytarabine to patients with previously untreated ANLL. Complete response rates in randomised comparative tri als were 53 to 67% after mitoxantrone with cytarabine and 37 to 70% af ter daunorubicin with cytarabine. In a major US study, significantly m ore patients achieved a complete response after I treatment cycle of m itoxantrone and cytarabine than after daunorubicin and cytarabine. Mit oxantrone has also been effective in inducing complete remissions in p atients with relapsed or refractory ANLL, mainly in combination with o ther antineoplastic agents. Overall survival appears similar after tre atment with regimens containing either mitoxantrone or daunorubicin in patients with ANLL, although there have been reports of trends toward s increased survival rates with mitoxantrone. The incidence of cardiot oxicity appears low in patients with ANLL who have received mitoxantro ne. Lower cardiotoxicity of mitoxantrone relative to daunorubicin has not been conclusively demonstrated in patients with ANLL, although tri als in patients,vith breast cancer have shown mitoxantrone to cause fe wer cardiac adverse effects than doxorubicin. This is of particular in terest in the elderly, as this group of patients is especially suscept ible to the effects of anthracycline-induced cardiac toxicity. Thus, m itoxantrone is a suitable first-line agent for the induction of remiss ion in patients with ANLL, with clearly demonstrated efficacy in patie nts aged 60 years and over.