Remission Induction Therapy

The backbone of remission induction therapy in AML patients consists of an anthracycline (daunorubicin or idarubicin) or anthracenedione (mitoxantrone) and cytosine arabinoside (ara-C),6-8,23,32,33,51-58 a regimen that has not changed in over two decades. Typically, daunorubicin is given at a dose of 45 mg/m2/day for 3 days, or idarubicin is given at a dose of 12 mg/m2/ day for 3 days, or mitoxantrone is given at a dose of 12 mg/m2/day for 3 days, in combination with ara-C, which is administered as a continuous infusion at 100 or 200 mg/m2/day for 7 days. (Frequently referred to as 7 + 3 chemotherapy.) In general, studies have compared different anthracyclines and anthracenediones, varied doses and schedules, and added additional agents with some improvement in CR rates, but without any effect on OS rates (Table 5.2). It is reasonable to tailor the aggressiveness of daunorubicin and ara-C administration

Figure 5.1 Approach to treating older AML patients

to the functional age of the older AML patient, with the understanding that, theoretically, some degree of efficacy may be compromised.

Comparing anthracyclines and anthracenediones

A phase III trial of 489 patients over 60 years of age compared an induction regimen consisting of mitox-antrone and ara-C to the standard of daunorubicin and ara-C.4 A CR was achieved by 47% of patients treated with mitoxantrone, compared to 38% of patients treated with daunorubicin, a difference that did not achieve statistical significance. Early and postinduction death rates were similar, as were toxicities, with the exception that those treated with mitox-antrone had a significantly higher rate of severe infections and a trend toward a longer duration of aplasia. OS was similar for both groups.

In older adults with AML, idarubicin may have advantages over daunorubicin that include reduced cardiac toxicity, circumvention of multidrug resistance (MDR), and oral administration.59 A number of trials have compared the two induction regimens,60-63 with the majority demonstrating a CR advantage in the idarubicin arm for younger adults, but no reproducible survival advantage. An overview of trials comparing idarubicin to daunorubicin for induction therapy showed similar overall induction failures in patients over 60 years of age receiving either of the two treatment arms; an improved CR rate in the idarubicin arm when compared to daunorubicin (50.5% vs 46.1%);

Randomized studies defining remission induction therapy in older adults
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