Higher dose of anthracycline improves overall survival of AML patients

Currently, the standard induction therapy for acute myeloid leukemia (AML) is a combination of anthracycline and cytarabine with complete remission rate of about 57% and overall survival of 15.7 months. The standard dose of anthracycline is 45-mg per square meter in patients under 60 years of age. Several studies have looked at efficacy of this drug at higher doses (up to 60-mg per square meter), resulting in improved remission rate with no significant change in overall survival.

The results of a phase-III clinical trial (ClinicalTrials.gov number, NCT00049517) were published in the September 23rd issue of the New England Journal of Medicine. The study involved 657 untreated AML patients between 17 and 60 years of age diagnosed within 6 months of the trial. Patients were given either the standard intravenous 45 mg or 90 mg of daunorubicine per square meter for 3 days and intravenous cytarabine at 100 mg per square meter per day for 7 days, started concurrently.

The findings indicate that intensifying anthracycline (daunorubicine) dose significantly improves complete remission rates (70.6% vs. 57.3%, P<0.001) as well as overall survival (23.7 vs 15.7 months, P=0.003). The high-dose regimen did not result in an increase rate of grade 3 to 5 hematologic and nonhematologic toxic effects, as compared to the standard dose regimen, and the death rate during treatment were essentially the same between the two treatment groups.

This study strongly suggests that a higher dose of anthracycline with cytarabine should be considered for treatment of AML patients under 60 years of age. With concurrent cytokine therapy, doses of up to 90 mg per square meter can be tolerated by young patients.

The published study can be found at NEJM: http://content.nejm.org/cgi/content/full/NEJMoa0905506?query=TOC