Postremission Therapy

No randomized trial has ever demonstrated that any amount of postremission therapy in older AML patients provides better outcomes than does no postremission therapy. That being said, the only studies demonstrating that long-term disease-free remission is possible in older AML patients have included remission induction and postremission ther-apy.4'5'7'27-29'32'35'69'83 Standard postremission therapy consists of a repeat of remission induction therapy, single-agent ara-C, or 2 days of an anthracycline or anthracenedione (the same type of drug given at the same doses as with remission induction therapy) combined with 5 days of ara-C, again given at the same dose as with remission induction therapy (frequently referred to as 5 + 2 postremission therapy), for one to two cycles.85

Intensive postremission chemotherapy

Younger adults with AML benefit from intensified doses of ara-C therapy in the postremission setting, while older adults, particularly those with liver or kidney abnormalities, do not (Table 5.3).5 730 The Cancer and Leukemia Group B (CALGB) studied 1088 patients with de novo AML who were randomized in first CR (following daunorubicin/ara-C remission induction therapy) to receive one of three postremission therapies: four courses of ara-C at 100 mg/m2/day for 5 days as a continuous intravenous infusion, at 400 mg/m2/ day for 5 days as a continuous intravenous infusion, and at 3 g/m2 in a 3-h infusion every 12 h on days 1, 3, and 5.7 Three hundred forty-six patients were over 60 years of age. Only 29% of older patients were able to tolerate all four courses of ara-C at 3 g/m2. Neurotoxicity occurred in 32% of older patients in the high-dose arm. Despite the higher rate of toxicity in older adults, disease-free and OS rates in this age group did not differ among the three postremission therapy arms.

A subsequent CALGB study randomized older AML patients in CR following remission induction therapy to one of two postremission regimens: ara-C at 100 mg/m2/day by continuous intravenous infusion over 5 days for four monthly courses, or ara-C at 500 mg/m2 every 12 h in combination with mitoxantrone for six doses, over four monthly courses.5 Although similar numbers of patients in each arm were able to complete all four postremission courses, survival was again similar at a cost of more toxicity in the higher dose ara-C arm. In another study, the mortality rate among older patients receiving high-dose postremission therapy was 57%, compared to a rate of 13% among younger patients.37 Given the toxicity of intensive postremission chemotherapy without a gain in survival, it is difficult to justify such treatment in older AML populations.

Randomized studies defining postremission therapy in older adults
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