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Is a Longer Schedule of Decitabine More Effective
Than a 5-Day Schedule in Older Patients With AML?
For older patients with treatment-
naïve acute myeloid leukemia
(AML), research has suggested
that a 10-day treatment schedule
of the hypomethylating agent
decitabine is associated with
better responses than a standard,
five-day schedule, but a new phase
II study published in Lancet Hae-
matology suggested no difference
in the safety and efficacy of each
schedule.
“Owing to the short half-life
of decitabine in vivo, treatment
for 10 days rather than five days
might be expected to capture a
larger proportion of leukemic
cells as they asynchronously enter
the S phase,” the authors, led by
Nicholas J. Short, MD, from the
University of Texas MD Ander-
son Cancer Center, explained.
However, based on these results,
either schedule can be consid-
ered “a reasonable, nonintensive
backbone regimen for future
investigational combinations with
novel agents.”
In this study, the investiga-
tors enrolled 71 patients aged 60
years or older who presented with
AML at MD Anderson Cancer
Center and whose disease was
“[Either
treatment
schedule]
can be a
reasonable,
nonintensive
backbone
regimen
for future
investigational
combinations.”
—NICHOLAS J. SHORT, MD
ASHClinicalNews.org
considered unsuitable for
TABLE. Response Rates
intensive chemotherapy
5-Day Decitabine
10-Day Decitabine
p Value
with an anthracycline
CR
8 (29%)
13 (30%)
0.88
plus cytarabine. Par-
CRp
3 (11%)
2 (5%)
--
ticipants were required to
CRi
1 (4%)
2 (5%)
--
have an Eastern Coopera-
CR + CRp + CRi
12 (43%)
17 (40%)
0.78
tive Oncology Group per-
formance status score of
Partial remission
0
1 (2%)
--
0 to 3 and adequate renal
No response
15 (54%)
22 (51%)
--
and hepatic function.
Early death
1 (4%)
3 (7%)
--
Study participants
CR = complete remission; CRp = complete remission without platelet recovery; CRi = complete remis-
were randomly assigned
sion with inadequate hematologic recovery
to receive intravenous
decitabine on one of two
schedules, each of which were
10-day decitabine regimens when
died during the study – three in
administered every four to eight
stratified by any of the following
the five-day group (sepsis, n=1;
weeks for up to three treatment
variables:
hemorrhage, n=1; infection, n=1)
cycles:
and six in the 10-day group (all
• cytogenetics (50% vs. 30%,
from infection).
• decitabine 20 mg/m 2 for
respectively; p=0.39)
Overall, early mortality (with-
in 30 days) was similar between
5 consecutive days over
• adverse-risk cytogenetics
each group: 4 percent (n=1/28)
a 1-hour period each day
(31% vs. 46%; p=0.37)
with the five-day schedule and 9
(n=28)
percent (n=4/43) with the 10-day
• de novo leukemia
schedule.
• decitabine 20 mg/m 2 for
(47% vs. 36%; p=0.50)
The authors concluded that a
10 consecutive days over
five-day schedule should be the
a 1-hour period each day
• secondary or therapy-related
optimum duration of decitabine
(n=43)
AML (38% vs. 44%; p=0.74)
therapy used in future trials of
combination regimens for AML,
The authors noted that patient
• TP53-mutated status
adding that “these results also
characteristics were well balanced
(29% vs. 47%; p=0.40)
have implications for the delivery
between each treatment arm and
of cost-effective care, as they
that substantial portions of pa-
Among the 29 patients who met
suggest that additional doses of
tients in each group had features
the primary endpoint, 19 relapsed
decitabine could raise treatment
associated with poor outcomes,
(8 in the 5-day group and 11 in the costs without providing addi-
including high-risk cytogenetics.
10-day group), for a one-year rate
tional benefit.”
After a median follow-up of
of relapse-free survival of 21 per-
Limitations of the single-
5.3 months (interquartile range
cent and 27 percent, respectively.
center study include the lack of
[IQR] = 2-11 months), there was
The median duration of
younger patients enrolled in the
no difference in the proportion
overall survival (OS), another
trial, as well as the exclusion of pa-
of patients who achieved the
secondary endpoint, was also
tients with relapsed or refractory
composite primary endpoint or
comparable with the two sched-
disease, which may limit the gen-
complete remission (CR), CR
ules: 5.5 months in the five-day
eralizability of the findings. The
with incomplete platelet recovery
group (IQR=2.1-11.7 months)
open-label study design also might
(CRp), or CR with incomplete
and 6.0 months in the 10-day
introduce bias. The study also was
hematologic recovery (CRi) be-
group (IQR=1.9-11.7 months). In
not adequately powered to identify
tween the treatment groups (43%
each group, researchers observed
differences in subgroups.
in the 5-day schedule vs. 40% in
a one-year OS rate of 25 percent.
The authors report financial
the 10-day schedule; p=0.78). Re-
Each treatment schedule
relationships with Pfizer, Janssen,
sponse information is presented
had a similar safety profile, the
Novartis, Abbvie, Seattle Genetics,
in the TABLE .
authors reported. Most of the
and others.
Patients who experienced
adverse events (AEs) were grade
CR, CRi, or CRp then received
REFERENCE
1 or 2, and the most common
consolidation therapy with
Short NJ, Kantarjian HM, Loghavi S, et al. Treatment with
grade 3 and 4 AEs in both groups
decitabine 20 mg/m 2 for five days
a 5-day versus a 10-day schedule of decitabine in older
were neutropenic fever (25%
for up to 24 cycles.
patients with newly diagnosed acute myeloid leukaemia:
a randomised phase 2 trial. Lancet Haematol. 2018
in the 5-day group and 33% in
Achievement of the primary
December 10. [Epub ahead of print]
the 10-day group) and infection
endpoint was not significantly
different between the five-day and (18% and 37%). Nine patients
ASH Clinical News
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