Biology Reference
In-Depth Information
The observation that treatment of anemia not sufficiently severe to require
red cell transfusion is associated with measurable improvements in functional
status and quality of life had been previously made in patients with chronic
renal failure undergoing dialysis and had been correlated with measurable
changes in mood,cognitive function, and exercise capacity [38-43]. (See
Chapter 9 for further discussion.) In light of this previous experience, the later
discoveries in the oncology setting were not surprising. Nevertheless, unlike
dialysis physicians, oncologists have not uniformly accepted the importance of
treating anemia to optimize quality of life. Currently <40% of the patients in
the United States who could clearly benefit from an increase in hemoglobin
concentration are treated. The reasons for this disparity are complex, but prob-
ably include both the higher doses (and hence per week cost) of erythropoiet-
ic agents required to treat patients receiving chemotherapy and profound short-
comings in our current approach to treating anemia in oncology (see below)
that need to be addressed.
Safety
In the early experience with rHuEPO in patients with renal failure receiving
dialysis, a rapid rise in hemoglobin concentration was associated with an
increased incidence of diastolic hypertension and, in severe cases, with result-
ant seizures. This syndrome was due to increases in blood volume associated
with increasing red cell mass in the absence of normal volume homeostasis.
The syndrome was found to be preventable by adherence to treatment para-
digms that were associated with gradual rather than rapid increases in hemo-
globin concentration, an appropriate approach in the setting of renal failure.
When erythropoietic agents were developed in patients with human immun-
odeficiency (HIV) infection or cancer, in whom very rapid rises in hemoglo-
bin concentrations are routinely encountered during red cell transfusions
uncomplicated by hypertension or convulsions, no rational basis was found to
assume that the much more modest rates of rise associated with even optimal
therapy would be a problem. Nevertheless, clinical trials of rHuEPO and dar-
bepoetin alfa have usually excluded patients with a history of seizures or
uncontrolled hypertension. In placebo-controlled trials of erythropoietic
agents in patients with cancer, epoetin alfa, epoetin beta, and darbepoetin alfa
have been safe and well tolerated,without a demonstrable increase in the inci-
dence of hypertension, seizures, or thrombotic events. Similarly, pure red cell
aplasia due to the development of cross-reacting antibodies to EPO that has
been observed in some patients on dialysis treated with Eprex-brand of epoet-
in alfa has not been observed in patients with cancer [44]. (See Chapter 14 for
further information on pure red cell aplasia.)
