Abstract
Objective
Older adults with acute myeloid leukemia (AML) tend to have worse complete remission
(CR) rates and overall survival compared to their younger counterparts. At least one
reason for this is increased expression of the multidrug resistance gene (MDR1). Dose
dense, high intensity chemotherapy may overcome the MDR1 effect, possibly when combined
with anti-CD33 monoclonal antibody gemtuzumab ozogamicin (GO,Mylotarg™), which has
been studied in older adults with relapsed AML. This phase I study was aimed at establishing
safety by defining a maximum tolerated dose (MTD) by treating older AML patients with
two cycles of dose-dense therapy with high dose cytarabine (HiDAC) combined with targeted
therapy using GO.
Materials and methods
Nine patients ≥60 years with newly diagnosed, untreated CD33+ AML with adequate renal and hepatic function,
and ECOG PS 0-2 were eligible. HiDAC was administered at two dose levels: 3000 mg/m2 every 12 h for 6 doses (cohort 1), or 9 doses (cohort 2). GO was administered at 6 mg/m2 on days 1 and 8.
Results
The MTD was HiDAC 3000 mg/m2 for six doses along with GO 6 mg/m2. All patients had grades 3–4 pancytopenia, and two patients developed reversible
grade 2 neurotoxicity. There were no cases of veno-occlusive disease. Seven of nine
patients had a complete response (CR or CRp).
Conclusions
There was no difference in relapse-free survival in our patients when compared to
historical data. However, despite high toxicity, two of nine patients treated in this
dose-dense fashion remained in CR for >60 months.
Keywords
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Article info
Publication history
Published online: March 14, 2012
Accepted:
February 7,
2012
Received in revised form:
January 12,
2012
Received:
October 8,
2011
Identification
Copyright
© 2012 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
