Fernandez, H. F. et al. Anthracycine dose intensification in acute myeloid leukemia. N. Engl. J. Med. 361, 1249–1259 (2009).

The current induction therapy for patients with acute myeloid leukemia (AML) is anthracycline plus cytarabine. Complete remission is achieved in 50–75% of patients and the addition of other drugs or dose intensification has not improved survival. Whether dose intensification for induction therapy in patients (<60 years of age) with AML might improve survival has not been addressed. In a randomized phase III trial by the Eastern Cooperative Group (ECOG), Fernandez and colleagues compared standard-dose and high-dose daunorubicin in young adults with AML.

The researchers randomly assigned 582 patients with AML, who had not been treated, to receive three once-daily doses of daunorubicin at the standard dose (45 mg/m2) or a higher dose (90 mg/m2), combined with cytarabine. Allogeneic hematopoeitic stem-cell transplantation, with or without a single dose of gemtuzumab ozogamicin, was offered to patients who experienced complete remission. Overall survival was the primary end point of the study and the median follow-up time was 25.2 months.

Patients treated with high-dose daunorubicin had a significantly higher rate of complete remission (70.6% versus 57.3%) and improved median overall survival (23.7 months versus 15.7 months) compared with patients who received standard-dose daunorubicin. Moreover, serious adverse events were similar in both groups, indicating that administration of high-dose daunorubicin has a similar safety profile as the standard-dose.

The researchers conclude that intensifying induction therapy with high-dose daunorubicin in young patients with AML significantly improved the rate of complete remission and the duration of overall survival; therefore, this treatment strategy should be considered as a standard of care in these patients.