“Our results suggest that the use of a DAC (daunorubicin and cytarabine plus cladribine) regimen as remission induction should be considered a new standard of care,” conclude Dr. Jerzy Holowiecki, with the Comprehensive Cancer Center M. Curie-Sklodowska Memorial Institute in Gliwice, and colleagues.
They note that induction chemotherapy consisting of 3 days of daunorubicin (DNR) and 7 days of cytarabine (AraC) has been the gold standard for treating AML since 1982. One possible way to intensify remission induction treatment, they explain, may be to add a purine analog such as fludarabine or cladribine.
They tested this strategy in 652 adults with untreated AML, who were assigned to receive induction with daunorubicin and cytarabine (DA), DA plus cladribine (DAC) or DA plus fludarabine (DAF).
The complete remission rate was significantly higher in the DAC arm (67.5%) than the DA arm (56%; p=0.01), but not in the DAF arm (59%), the team found.
Similarly, overall 3-year survival rates were 45% in the DAC group compared with 33% in the DA arm and 35% in those receiving the DAF regimen, the report indicates. Median survival was 10 months longer in the DAC group than the DA group.
The authors note that although cladribine and fludarabine have similar characteristics, their mechanisms of action are not the same. “Moreover, in contrast to other purine analogs, cladribine acts against both proliferating and nonproliferating cells,” they explain.
Summing up, Dr. Holowiecki and colleagues conclude, “We demonstrated that the addition of a third component to the standard induction regimen consisting of the combination of DNR and AraC improves the survival of patients age 60 years or younger with newly diagnosed AML. This has been demonstrated with respect to cladribine but not fludarabine.”