Evidence and Efficacy
This regimen has a very limited role in the treatment of acute myeloid leukaemia (AML), probably only in patients over the age of 60 or patients in whom there is a contraindication to high dose cytarabine regimens (e.g. previous significant cerebellar toxicity).
The pivotal CALGB trial of Mayer et alr in patients up to the age of 60 compared 100 mg/m2, 400 mg/m2 and 3 g/m2 doses of cytarabine in consolidation and showed a statistically significant chance of complete remission at 4 years for the 3 g/m2 dosing (Q12H days 1,3,5 IVI 3 hours) compared to the lower doses of cytarabine. Current best practice would be to consolidate with high dose cytarabine containing regimens in the patient population up to the age of 60.r
The optimal management of patients age greater than 60 is not clear however consolidation with an anthracycline and conventional dose cytarabine appear a reasonable option, at least up to the age of 74.r Wiernik et alr included adults of all ages and randomized to two consolidation cycles with standard dose cytarabine (100 mg/m2 D1-5) plus daunorubicin (45 mg/m2) or idarubicin (13 mg/m2) (both for 2 days) and showed a significant survival benefit of idarubicin over daunorubicin. The idarubicin 12 mg/m2 corresponds to the dose used by Berman et al4 in a randomized trial of daunorubicin (50 mg/m2) versus idarubicin (12 mg/m2), showing a survival superiority of idarubicin in patients up to the age of 60.
In summary, the main place of this regimen is in consolidation chemotherapy (typically two cycles) in patients over the age of 60. It usually should not be used in the younger patient population where more intensive consolidation regimens are indicated in most cases. Randomised trial data comparing this regimen to other consolidation strategies is limited.
A search of the literature found limited evidence to support the use of cytarabine and idarubicin 5-2 in the consolidation treatment of AML. The expert reference panel supported publication of the protocol on the basis of the information summarised below. The committee was most strongly influenced by the study by Wiernik et al3 and Berman et al.r
Source |
Study & Year Published |
Supports Use |
Is the dose and regimen consistent with the protocol? |
Comments |
Randomised trials |
Wiernik et al. 1992 |
Yes |
No |
Idarubicin 13 mg/m2 days 1-2 and cytarabine 100 mg/m2 days 1-5 for 2 cycles |
|
Berman et al. 1991 |
Yes |
No |
Idarubicin 12 mg/m2 days 1-2 and cytarabine 200 mg/m2 days 1-4 for 2 cycles |
Observational studies |
N/A |
N/A |
N/A |
- |
Case series |
N/A |
N/A |
N/A |
- |
Guidelines |
Date published/revised |
Supports Use |
Is the dose and regimen consistent with the protocol? |
Comments |
NCCN |
Mar 2014 |
Yes |
N/A |
- |
BCCA |
N/A |
N/A |
N/A |
- |
ESMO |
2013 |
N/A |
N/A |
- |
Toxicity
There was an increased incidence of dysphagia occurring in 15% of patients receiving idarubicin versus 0% in patients receiving daunorubicin but otherwise toxicity was similar in both groups during consolidation therapy in the Wiernik study.r There was an increased incidence of diarrhoea, hyperbilirubinaemia, elevation of transaminases, alkaline phosphatase and urea, infections and more prolonged myelosuppression in idarubicin arm compared to daunorubicin arm in consolidation therapy in the Vogler study.
Haematological toxicity during consolidation therapy:r

© Blood 1992