LOS ANGELESMany, if not most, oncologists agree that erythropoietic
therapy can lower the need for transfusions and improve quality-of-life.
This is especially true when cancer patients who suffer from fatigue have
their hemoglobin levels raised from 10 g/dL or less to 12 g/dL or more. Why
then are less than 30% of patients who should receive erythropoietic therapy being treated with it?
(See Table 1.)
There are several reasons for this (if reimbursement were not an issue),
according to John A. Glaspy, MD, MPH, of the University of California School
of Medicine in Los Angeles.
- The significant numbers of non-responders blunt enthusiasm for
erythropoietic therapy in the oncology community and weaken its
cost-effectiveness as a treatment strategy.
- Physicians may not be receptive to quality of life as an endpoint.
- Erythropoietic therapy has not always been easy to administer.
Recombinant human erythropoietin (rHuEPO) is made up of several isoforms
that differ in the number of glycosylation sites and sialic acids present,
from 9 to 14. The greater the number of sialic acid molecules present in an
isomer, the greater the potency of the agent in vivo (see Figure 1).
"That led to an effort that spanned years, through site-directed
mutagenesis, to develop new erythropoietin genes that added glycosilation
sites," Dr. Glaspy explained. "That search ended in darbepoetin
alfa (Aranesp), which has two additional glycosylation sites and up to eight
additional sialic acids (see Figure 2). So instead of a maximum of 14, there
are a maximum number of 22 that are added to the protein." Compared to
rHuEPO, darbepoetin alfa is more potent in vivo.
Meaningful comparison of study results requires agreement on how outcomes
Hemoglobin response is defined as a hemoglobin increase greater than 2 g/dL
(from baseline) in the absence of red blood cell transfusions within the
preceding 28 days. But what about a baseline hemoglobin of 11 that rose to
12? Although that gain would put the hemoglobin at a normal level, it didn’t
fit the definition of a hemoglobin response because the hemoglobin level
only rose 1 g/dL. That change is classified as a hemoglobin correction,
defined as hemoglobin greater than 12 g/dL in the absence of red blood cell
transfusions within the preceding 28 days. Together, the hemoglobin response
and the hemoglobin correction can be used to calculate the hematopoietic
response, defined as a hemoglobin increase greater than 2 g/dL (from
baseline) or hemoglobin greater than or equal to 12 g/dL. The mean change in
hemoglobin refers to the mean change from baseline, in the absence of any
red blood cell transfusion within the previous 28 days.