Recombinant human erythropoietin
(epoetin alfa, Epogen, Procrit) administered
to patients with non-small-cell
lung cancer (NSCLC) who are undergoing
chemotherapy has been found
to significantly reduce the incidence of
anemia, compared with best supportive
care, and to improve quality of life.
Robert Milroy, MD, of Stobhill General
Hospital, Glasgow, United Kingdom,
presented the study findings at
the 10th World Conference on Lung
Cancer (abstract O-253).
"The biggest reduction in quality of
life occurs when Hb drops from 12 to
11 g/dL," Dr. Milroy said. "We wanted
to see if it is possible to prevent anemia
in patients by early intervention with
epoetin alfa [to possibly] improve quality
of life and even survival."
The international, phase III study
randomized 380 patients with stage
IIIb (48%) or stage IV (51%) (1%
unspecified) NSCLC who were receiving
cisplatin (Platinol)-based or carboplatin
Eligibility criteria included
hemoglobin of 15 g/dL or less for men
and 14 g/dL or less for women.
Patients were randomized on a 1:1
basis to receive 10,000 IU epoetin alfa
subcutaneously three times weekly or
best supportive care, which included
chemotherapy. Treatment with epoetin
alfa was initiated when hemoglobin
dropped below 13 g/dL in men and
below 12 g/dL in women.
Patients whose hemoglobin levels
were at 13 g/dL (men) and 12 g/dL
(women) at study entry (the immediate
treatment group) received epoetin
alfa immediately. Other patients started
chemotherapy and began epoetin
alfa when their hemoglobin dropped
below the trigger points (the delayed
Epoetin alfa was administered for
up to 4 weeks following the last cycle of
chemotherapy. The study duration was
28 weeks. The mean hemoglobin level
at study baseline was 12.7 g/dL (range
7.7 to 15.3 g/dL). Quality of life was
assessed with the FACT-An (Functional
Assessment of Cancer Therapy-
Results show that overall, 8.9% of
patients treated with epoetin alfa required
blood transfusions, compared
with 24.3% of those receiving best supportive
care (P < .0001). This represents
a transfusion reduction of more
There was also a significant difference
between the active treatment and
best-supportive-care groups with respect
to stabilized hemoglobin. In the
entire study population, patients treated
with epoetin alfa had stabilized hemoglobin
at greater than 12.5 g/dL
throughout the study period, whereas
patients in the best-supportive-care
group experienced a steady decline
(P < .001).
A subgroup analysis of the immediate
and delayed epoetin alfa treatment
groups showed that the strategy of early
use did work, "particularly the early
treatment in patients with low hemoglobin
at the outset," Dr. Milroy said.
Immediate epoetin alfa treatment
maintained hemoglobin levels during
chemotherapy, despite significantly
fewer blood transfusions (P < .001),
Data on the delayed-treatment
group showed a fall in hemoglobin
initially, followed by stabilization. "The
point is that in the treated patients,
epoetin alfa was able to maintain hemoglobin
of between 12.5 and 12.7
g/dL. In the best-supportive-care control
arm, the patients became significantly
anemic," Dr. Milroy said. "The
strategy to prevent anemia worked."
Quality of Life
Immediate epoetin alfa intervention,
but not delayed treatment, reduced
the decline in quality of life.
"This may be because the delayed
group had started with normal hemoglobin
and then drifted down by over
a gram before they could start epoetin
alfa," Dr. Milroy said.
The most striking survival finding,
he said, was that the patients in the
immediate- treatment group, who were
anemic at the study outset, had much
worse survival regardless of epoetin
alfa treatment, compared with patients
in the delayed treatment group. The
results show a highly statistically significant
difference between the immediate
and delayed treatment groups'
survival of 24.8% and 48.1%, respectively
(P < .0001).
"We all know hemoglobin is an individual
prognostic factor, but this is a
striking change," Dr. Milroy said. "We
didn't see any benefits from epoetin
alfa either in the immediate or the
delayed arms in terms of survival benefits.
We were disappointed by that."
However, the data showed a 20% improvement
in overall survival among
patients with baseline hemoglobin of
13 g/dL or more (male) and 12 g/dL or
more (female), compared with patients
who had lower baseline hemoglobin.
"The strategy works; epoetin alfa
was able to keep patients' hemoglobin
levels up and prevent anemia, and that
was consistent for both the immediate
and delayed treatment groups," Dr.