SIDEBAR: Further Reflections on a Successful Trial

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The authors are to be congratulated for successfully conducting a randomized study of FLAG (fludarabine, cytarabine, and granulocyte colony-stimulating factor [Neupogen]) vs FLAG plus liposomal daunorubicin (DaunoXome) in relapsed pediatric acute myeloid leukemia (AML). The difficulty in conducting such a study must not be underestimated; nearly 400 patients from 20 countries were enrolled over a period of more than 7 years.

Neither the 4-year overall survival rate nor the complete remission rate differed between the two treatments, although early response was better in the FLAG/liposomal daunorubicin arm. Interestingly, however, for patients with favorable cytogenetics, treatment with FLAG/liposomal daunorubicin resulted in an overall survival rate of 82%, vs 58% with FLAG (P = .04). The authors comment that this difference may be the result of patients with a more favorable prognosis benefiting from more-intensive therapy in general.

Critical Lessons

There are two critical lessons from this study. First, we must strive to continue to improve the outcome of front-line treatment of pediatric AML, because the prognosis after relapse remains unsatisfactory. Second, we can and must conduct rigorous studies of new therapies in AML and other diseases, even when such studies are difficult and time-consuming.

For both arms of this study, overall survival was better than would likely have been predicted based on historical controls. Without randomization, the improvement might have been erroneously attributed to the addition of liposomal daunorubicin to FLAG. Thus, although the clinical benefit of liposomal daunorubicin appears to be modest at best in this setting, the study overall should be considered a success because of the important information it provides. ■

Disclosure: Dr. Berg reported no potential conflicts of interest.

Dr. Berg is Professor of Pediatrics at Baylor College of Medicine and Director of Clinical Research at Texas Children’s Cancer Center, Houston.

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