cancer-related anemia improves quality
of life and may have other potential therapeutic
benefits for cancer patients, according
to speakers at a cancer-related
anemia symposium presented in conjunction
with the 28th Annual Congress of the
Oncology Nursing Society. The expert
panel also discussed the need for earlier
intervention with flexible dosing regimens
and outlined potential future applications
of erythropoietic agents.
Changing Transfusion Guidelines
"Before 1980, red blood cell transfusions
were given frequently because there
wasn't much worry about transfusions.
We would give people transfusions at a
hemoglobin level under 10 g/dL," said
David H. Henry, MD, clinical associate
professor of medicine at the University of
Pennsylvania School of Medicine in Philadelphia.
In the 1980s, concerns about
transfusion-related diseases and the scarce
blood supply were responsible for changing
transfusion guidelines to 8 g/dL.
"Now we're starting to think about
early intervention, perhaps under 12
g/dL, and treating up to and including 12
g/dL, as well as the potential therapeutic
efficacy in cognitive functioning and possible
links to survival," Dr. Henry added.
The impact of fatigue on quality of life
has been documented. Based on data cited
by Dr. Henry, 30% of patients experience
daily fatigue, 57% have difficulty in socializing
with family and friends because
of fatigue, and 75% have to alter their
work status because of their fatigue.
In 2002, Crawford and colleagues
showed that quality of life improves with
increasing hemoglobin levels (Figure 1).
"When you take hemoglobins from 6 g/dL
all the way up to 12 g/dL, quality of life
steadily improves," Dr. Henry suggested.
The greatest functional improvement occurred
among patients at 10 g/dL or higher,
and most of the improvement was at
11, 12, and up to 13 g/dL. "Females are
supposed to be at 12 g/dL and above, and
males are supposed to be at 13.5 g/dL and
above, so there must be a reason that
nature wants us at that set point," Dr.
Today, agents such as epoetin alfa
(Procrit) and darbepoetin alfa (Aranesp)
can reduce the need for transfusions and
significantly improve fatigue and quality
of life among cancer patients. Approved
in 1993, epoetin alfa significantly reduces
the need for transfusions, causes a rapid
rise in hemoglobin level by about 1 g or
more by week 4 (Figure 2), can be titrated
for early dose escalation after 4 weeks, and
improves quality of life independent of
Approved in 2002, darbepoetin alfa
also reduces the need for transfusions,
causes a rise in hemoglobin levels (Figure
3), and improves quality of life in responders.
It has a longer half-life than
epoetin alfa but less epoetin alfa-receptor
binding. Titration can be undertaken after
6 weeks. In addition, therapy may improve
tumor response rate, patient survival,
and cognitive function.
However, Dr. Henry noted that about
one-third of patients do not respond to
erythropoietic agents, and the reason for
this lack of response is unknown.
Dosing Issues, Prognostic Significance
Lillian M. Nail, PhD, RN, professor
and senior scientist at the Oregon Health
and Science University School of Nursing
in Portland, explored dosing issues and
reviewed research on the effects of epoetin
alfa on quality of life, patient response,
and treatment outcome. The approved
of patients with head and neck cancer
(91% of whom were men) who were treated
with neoadjuvant chemoradiation followed
In their secondary analysis, researchers
divided the population into three
groups. Group 1 consisted of patients with
pretreatment hemoglobin levels of at least
14.5 g/dL. These patients did not receive
epoetin alfa because it had not been approved.
Group 2 included patients with a
pretreatment hemoglobin level of less than
14.5 g/dL. These patients received epoetin
alfa during all or part of their therapy,
whenever their hemoglobin levels dropped
below 12.5 g/dL. Group 3 had a pretreatment
hemoglobin level of less than 14.5
g/dL but did not receive epoetin alfa because
it had not been approved.
The 2-year survival for the group with
the high pretreatment hemoglobin levels
was 81%, compared with 60% for the
group with the lower pretreatment hemoglobin
levels who did not receive epoetin
alfa. Group 2 also had a significantly longer
median survival than did group 3, and
the 2-year survival for group 2 was 88%.
These results suggest that low pretreatment
hemoglobin levels are a negative
prognostic factor for survival, although a
larger prospective trial is needed for firm
conclusions about the data, Dr. Barsevick
There is also evidence to suggest that
epoetin alfa can attenuate or prevent cognitive
dysfunction in cancer patients undergoing
chemotherapy. "Even at standard
doses, adjuvant chemotherapy
appears to have distressing effects on some
aspects of cognitive functioning, including
concentration and memory, as well as
attention, speed of information processing,
and motor speed," Dr. Barsevick explained.
These effects are independent of
mood changes or self-reported problems.
O'Shaughnessy and colleagues examined
the effects of epoetin alfa in breast
cancer patients undergoing anthracycline
treatment. They found that 18% of patients
receiving epoetin alfa experienced
improvement in cognitive function before
the fourth cycle of chemotherapy,
compared with only 2% of the placebo
group. Moreover, only 4.5% of the epoetin
alfa group experienced deterioration
in cognitive function, compared with almost
14.0% of the placebo group. These
results demonstrate that for breast cancer
patients receiving chemotherapy, treatment
with weekly epoetin alfa improved
or prevented decline in cognitive function
in comparison to a placebo control.
Furthermore, epoetin alfa may have a
neuroprotective effect, shielding the brain
from the negative effects of chemotherapy.
Animal studies of induced brain
ischemia and preliminary studies of
patients suffering acute ischemic stroke
also support a direct neuroprotective effect
of epoetin alfa, concluded Dr.