Anthracycline Dose Intensification in Acute Myeloid Leukemia (AML)
Slides from the journal article and transcribed comments from recent interviews with
Gail J Roboz, MD (10/6/09) and Steven D Gore, MD (10/8/09) below
Presentation discussed in this issue:
Fernandez HF et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med 2009;361(13):1249-59. Abstract
GAIL J ROBOZ, MD: This was a beautifully done study, which clearly shows that the higher daily dose of anthracycline at 90 mg/m2 is better than the 45 mg/m2 dose. The only problem with the study is that it uses a control arm of 45 mg/m2, which is a lower dose than a lot of people use for AML. It has been standard for several years to use 60 mg/m2 as the induction dose of daunorubicin. Many physicians question whether daunorubicin 90 mg/m2 is better than 60 mg/m2, and unfortunately, this study did not answer that question. Physicians who have been using 45 mg/m2 as their standard dose should change to 90 mg/m2. For those who have been using 60 mg/m2 as their off-study treatment dose for induction, they do not know what to do. I would say that the experts are divided as to whether or not this represents a new standard.
STEVEN D GORE, MD: This is an important study, which demonstrates that a higher dose of anthracycline had an effect on overall survival in patients, particularly those with favorable or intermediate cytogenetics. However, it did not have an effect in patients with high-risk cytogenetics or in patients who had FLT3 mutations or MLL partial tandem duplication. I believe that this is a bit of a game changer, potentially, for patients with intermediate- or lower-risk AML who are receiving standard induction regimens. The problem, of course, is that you do not always have all of this cytogenetic and mutational analysis information before therapy is initiated. I believe the default will be that everybody should probably receive the higher dose until proven otherwise. If you find out the patients are in one of these groups that do not benefit, you would not necessarily continue with the higher dose during consolidation.
Dr Roboz is Associate Professor of Medicine and Director of the Leukemia Program at Weill Medical College of Cornell University at NewYork-Presbyterian Hospital in New York, New York.
Dr Gore is Professor of Oncology at Johns Hopkins University in Baltimore, Maryland.