A randomized study of intermediate versus conventional-dose cytarabine as intensive induction for acute myelogenous leukaemia.

The optimal dose of cytarabine for induction chemotherapy is unknown. Most studies have utilized doses of 100-200 mg/m2/d, although higher doses have been proposed to increase the concentration of the active metabolite ara-CTP within leukaemia cells. To address this question 101 adults with newly diagnosed acute myeloid leukaemia were randomized to receive treatment with daunorubicin and either conventional-dose cytarabine (200 mg/m2/d by continuous infusion) or an intermediate-dose of cytarabine (500 mg/m2 every 12 h). 36/51 (71%) patients assigned to conventional-dose cytarabine achieved complete remission compared to 37/50 (74%) who achieved remission with intermediate-dose cytarabine (P = 0.9). Patient age significantly affected remission rate. 8/17 patients age greater than 60 assigned to conventional-dose cytarabine and 10/17 assigned to intermediate-dose cytarabine achieved complete remission compared to 27/33 patients under age 60 assigned to the conventional dose and 28/34 patients assigned to the intermediate dose arm (P = 0.004). Actuarial 4-year disease-free survival for patients assigned to conventional-dose cytarabine was 20 +/- 16% versus 28 +/- 17% for patients assigned to intermediate-dose cytarabine (P = 0.9). We conclude that intermediate dose cytarabine did not substantially improve results of induction chemotherapy for acute myeloid leukaemia.