(ChemotherapyAdvisor) – Treatment with liposomal daunorubicin plus fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG) has resulted in the best outcome for children with relapsed core-binding factor acute myeloid leukemia (AML) to date, results of the first phase 3 randomized trial in this population concluded in the Journal of Clinical Oncology published online January 14, 2013.

Among children with AML, survival rates are greater than 60%. The most frequent type of treatment failure is relapse, with the probability of overall survival of 16% to 34%. Optimal reinduction therapy for this population remains unknown.

Based on studies suggesting liposomal daunorubicin is effective and less cardiotoxic, the International Berlin-Frankfurt-Münster Study Group randomly assigned 394 patients with relapsed or primary refractory non−French-American-British type M3 AML younger than 21 to FLAG or FLAG plus liposomal daunorubicin in the first reinduction course.

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Primary end point was status of the bone marrow sampled shortly before the second course of chemotherapy, defined as day-28 bone marrow. Median follow-up was 4 years.

“The complete remission (CR) rate was 64%, and the 4-year probability of survival was 38%,” Gertjan J.L. Kaspers, MD, PhD, Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, the Netherlands, and colleagues reported.

The day-28 bone marrow status, available in 359 patients, was considered good (≤20% leukemic blasts) in 80% of patients in the FLAG/liposomal daunorubicin arm and 70% for those in the FLAG arm (P=0.04).

The CR rate was 69% with FLAG/liposomal daunorubicin and 59% with FLAG (P=0.07); however, overall survival was similar. When patients were examined by core-binding factor status, those in the FLAG/liposomal daunorubicin arm had a probability of survival of 82% versus 58% for FLAG alone (P=0.04).

Except for a modest increase in skin toxicity, the increased antileukemic activity with FLAG/liposomal daunorubicin was not associated with increased toxicity, the authors reported, although “concerns for late cardiotoxicity associated with higher cumulative doses of anthracyclines and related drugs are valid.” Due to its pharmacology, liposomal daunorubicin might be less cardiotoxic.

The report details guidelines for long-term follow-up, with “special attention to cardiac function.”