SAN FRANCISCOThe anemia drug darbepoetin alfa (ARANESP)
effectively alleviates anemia, boosting hemoglobin counts and reducing the need
for red blood cell transfusions, according to the results of two separate
In a study conducted among 177 patients with solid tumors,
darbepoetin raised hemoglobin more than 2 g/dL. Weekly doses of darbepoetin
were tested for 12 weeks at five different doses concurrently with
chemotherapy. Darbepoetin is a supersialated protein that binds to the
erythropoietin receptor and stimulates erythropoiesis by the same mechanism as
rHuEPO. The control group received rHuEPO for 6 weeks, along with chemotherapy.
"The bottom line is that darbepoetin worked. It increased
the blood counts of patients significantly. And the higher the dose of
darbepoetin, the more the blood counts improved," said lead researcher
John Glaspy, MD, MPH, director of the Bowyer Oncology Center at the University
of California at Los Angeles.
Darbepoetin was given in doses of 0.5, 1.0, 1.5, 2.25, and 4.5
µg/kg/week starting with the first cycle of chemotherapy. At the lowest dose
(5 µg/kg), darbepoetin boosted hemoglobin by a mean of .96 g/dL. The mean
change in hemoglobin counts at the highest dose (4.5 µg/kg) was 2.6 g/dL.
The study showed dose-dependent trends in the mean change of
hemoglobin and the proportion of patients achieving a hemoglobin response and
correction. At 2.25 µg/kg, 50% of patients achieved a hemoglobin correction
and at 4.5 µg/kg, this rose to 70%.
As part of the study, participants answered questions on a
Health Related Quality of Life (HRQOL) survey at 1 week, and again at 4, 8, and
12 weeks after chemotherapy and anemia therapy had begun. Selected domains of
HRQOL were measured by the Functional Assessment of Cancer Therapy (FACT)
Anemia and FACT-General scale. The results revealed that the patients’
functional abilities and fatigue score increased as their hemoglobin went up
with darbepoetin therapy. At 0 change in hemoglobin, the average fatigue score
was -1.5, while at more than 2 g/dL change in hemoglobin, the score improved
The number of red blood cell transfusions needed by patients on
each drug was also dramatically different22% of patients on rHuEPO compared
to only 2% to 7% of patients on darbepoetin. Yet, as Dr. Glaspy noted:
"The object of the study was not to compare darbepoetin with rHuEPO. We
need to find out if darbepoetin is effective and maintain a database on
Although not yet approved by the Food and Drug Administration,
darbepoetin has been shown to have a two- to threefold longer serum terminal
half-life than rHuEPO in patients with chronic renal failure. Dr. Glaspy’s
work has also shown that darbepoetin has an extended serum terminal half-life
in oncology patients receiving chemotherapy. In this study, darbepoetin was
given only once weekly, while rHuEPO has to be administered 1 to 3 times
Darbepoetin was well tolerated by most patients in the study.
"Our data showed that darbepoetin is a safe drug," Dr. Glaspy said.
The type and frequency of adverse events in patients receiving darbepoetin were
consistent with those experienced by patients with cancer receiving cytotoxic
chemotherapy and comparable to those of patients receiving rHuEPO. The most
frequently reported adverse events in both treatment groups included fatigue,
nausea, vomiting, diarrhea, and fever. No anti-darbepoetin antibodies were
All the patients in the study were anemic at outset, had more
than a 6-month life expectancy, had solid tumors, were iron replete, and had
adequate renal and liver function. None had more than two red blood cell
transfusions within 4 weeks of randomization, and no rHuEPO therapy within 8
weeks of randomization.
Anemia is generally considered an underreported diagnosis in
cancer patients. Yet the incidence of anemia in cancer patients may be as high
as 50% to 60%. Cancers associated with the highest incidence of anemia include
lymphomas, lung cancer, and ovarian or genitourinary tumors. There currently
are no universal guidelines for the treatment of anemia in cancer patients.
The results of the study indicate that darbepoetin may be
effective in treating the anemia in cancer patients, according to Dr. Glaspy.
"We know that darbepoetin works in the setting of our study. Additional
data with higher doses of the drug should give us an even better picture of
darbepoetin’s safety and efficacy," Dr. Glaspy concluded.
Reduction in Dosing
In a multicenter international study, darbepoetin was shown to
be effective when given just once every 3 weeks to patients with solid tumors.
This represents a substantial reduction in the dosing schedule compared to
rHuEPO, administered 1 to 3 times every week.
"The potential for being able to treat anemia in cancer
patients with injections substantially less often than currently given could
dramatically increase the number of anemia patients treated for this
underrecognized disease," said lead researcher Dusan Kotasek, MD, of the
Ashford Cancer Centre in Ashford, Australia. Only about one third of anemic
cancer patients on chemotherapy receive treatment for anemia, Dr. Kotasek
In the double-blind placebo-controlled study of 163 patients
(131 received darbepoetin, 32 received placebo), there was a dose-dependent
response to darbepoetin when compared with placebo. The incidence of red blood
cell transfusions also decreased as the dose of darbepoetin was increased.
Patients receiving darbepoetin were treated at doses of 4.5,
6.75, 9, or 13.5 µg/kg over 12 weeks. At the highest dose, hemoglobin counts
rose an average of 1.5 g/dL, and in some patients, hemoglobin counts went up as
much as 2 or 2.5 g/dL. The frequency of blood transfusions in the darbepoetin
group was 22% to 25%; half that seen in placebo patients (44%).
"You have to achieve a fairly high dose to see a real
benefit, especially in hemoglobin response," Dr. Kotasek stated. "We
believe that we haven’t yet reached the most effective dose. If we gave
higher doses, we could probably get even better results." Dr. Kotasek said
he and fellow researchers will aim to increase the darbepoetin dose given to
patients in continuing studies.
More than two thirds of the study participants were female with
a wide range of cancers, including breast, gynecologic, and gastrointestinal
cancers. All patients were receiving chemotherapy and had developed anemia.
None of the patients had received rHuEPO therapy within 8 weeks of
randomization, and none had more than two red blood cell transfusions within 4
weeks of randomization.
Dr. Kotasek and fellow scientists revealed that darbepoetin was
very well tolerated by patients when given once every 3 weeks. There were no
unusual side effects, and adverse events were consistent with those experienced
by patients with cancer undergoing chemotherapy, and comparable to those of
patients receiving rHuEPO. No darbepoetin antibodies were detected, and trough
concentrations of the drug indicated no evidence of accumulation over time.
The use of darbepoetin could make it much easier for patients
to receive anemia therapy, Dr. Kotasek said. "They would be getting fewer
injectionsand avoiding any unneeded jabs. There wouldn’t be the need for
additional supervision at more frequent anemia therapy sessions. And
darbepoetin could be given in a timely manner during the patient’s
chemotherapy appointments. It would be very convenient," Dr. Kotasek
"Giving darbepoetin to cancer patients with anemia is
certainly an effective way of maintaining hemoglobin and avoiding blood
transfusions, and our research indicates that it’s very safe," he added.