This protocol has been superseded because it is not commonly used in clinical practice.
HAM is a regimen that was originally designed to combine an anthracycline which has low dose cardiotoxicity (mitozantrone) with high dose cytarabine in patients with relapsed or refractory AML.r This was based on the principle that cytarabine combined with an anthracycline is effective in AML, that cytarabine may have a conditioning effect for subsequent anthracyclines, that there is in vitro synergy between the two agents and that mitozantrone has antileukaemic effect as a single agent.
As with any second line regimen in AML, there is limited evidence to support a specific dosing regimen of these drugs in combination (given a lack of consistent regimens in published studies) and there is no randomised control trial specifically comparing this regimen alone with any other regimen. The most consistent HAM regimen has been published in a series of German studiesrrr (the dosing schedule in these studies serve as the basis of the current eviQ protocol).
It should be noted, however, that there have been many alternative schedules with respect to the cytarabine dose (low, intermediate and high) and the mitozantrone schedule.rrr There appears to be no superficial difference in outcomes with these varying schedules.
The most recent major study using the HAM regimen was in previously untreated AML patients comparing a TAD regimen of thioguanine (100 mg/m2 days 3 to 9), cytarabine (1200 mg total dose) and daunorubicin (60 mg/m2 on days 3 to 5) and then the HAM regimen of cytarabine (3 g/m2 days 1 to 3) and mitozantrone (10 mg/m2 on days 3, 4 and 5) on recovery to two sequential courses of the HAM regimen.r Patients in both groups were subsequently randomised to receive either 3 years of maintenance or to a busulphan/cyclophosphamide based autograft.
In current practice, it would tend to be used either as a salvage regimen, or in patients in whom a less cardiotoxic anthracycline may be preferred.
A search of the literature found limited evidence to support the use of HAM in the 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 Buchner et alrr and Hiddemann et alr studies.
Source |
Study & Year Published |
Supports Use |
Is the dose and regimen consistent with the protocol? |
Comments |
Phase II trials |
Hiddemann et al 1987 |
Yes |
No |
Cytarabine 3g/m2 days 1 to 4 and mitozantrone 12mg/m2 days 3,4,5. Dose escalation schedule also recommended |
Randomised trials |
Buchner et al 2003 & 2006 |
Yes |
Yes |
For previously untreated patients |
Case series |
N/A |
N/A |
N/A |
- |
Observational studies |
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 |
N/A |
N/A |
- |
BCCA |
N/A |
N/A |
N/A |
- |
ESMO |
2013 |
N/A |
N/A |
- |
Efficacy
The complete response rate was equivalent in both the TAD-HAM and the HAM-HAM groups at 61% versus 60%. The survival curves are indicated in the figure below, with no significant differences in the randomised induction arms (or in the randomised maintenance arms: data not shown).r
© Journal of Clinical Oncology 2006
Toxicity
The toxicity from the above study is indicated in the table below:r
© Journal of Clinical Oncology 2006