Biology Reference
In-Depth Information
transfusions. In part because anemia was assumed to be relatively asympto-
matic in patients with cancer, the potential benefit to patients of these higher
hemoglobin concentrations was not initially explored.
In the first large, open-label, uncontrolled, study of rHuEPO done in the
United States, chemotherapy patients receiving epoetin alfa at a starting dose
of 150 U/kg three times a week completed a simple linear analog scale assess-
ment of their energy level,ability to do daily activities, and overall quality of
life at the initiation and termination of epoetin therapy [22]. The observed
mean score for each of these domains increased significantly during epoetin
alfa therapy over a time frame in which the mean hemoglobin concentration
for these patients was increasing from approximately nine to approximately
11 g/dL. Simultaneously, the results of a large survey of patients with cancer
suggested that fatigue was as great a contributor to symptom burden in these
patients as was pain, and that fatigue impaired several domains of quality of
life [34, 35]. Both observations, that fatigue decreased and quality of life
increased when mild and moderate anemias were successfully treated in this
patient population and that fatigue was an unappreciatedly important cause of
functional decline in cancer patients, were subsequently confirmed in similar
studies [23, 27, 36]. These findings led to a paradigm shift in the approach to
erythropoietic therapy. Severe anemia (hemoglobin concentration <8 g/dL) is
often treated with transfusions; because erythropoeitic agents decrease trans-
fusion risk,they can be thought of as alternatives to transfusions. If improve-
ments in hemoglobin concentration in the range of mild and moderate anemias
(<8 to <11 g/dL), which are not treated with transfusions, are associated with
improvements in functional status and a symptom important to patients, ery-
thropoietic agents are much more than alternatives to red cell transfusion and
their use may be beneficial even to patients whose anemia will not become
severe enough to warrant transfusion.
The effects of erythropoietic therapy on fatigue level and quality of life have
been assessed in several appropriately powered randomized trials in patients
with cancer receiving chemotherapy [20, 21, 29]. In these studies, erythropoi-
etic therapy has been associated with a significant improvement in quality of
life and decrease in fatigue compared with the cohorts receiving placebo. In
general, the magnitude of the quality of life improvement has correlated with
the magnitude of the improvement in hemoglobin value. A retrospective analy-
sis of data from two large, community-based trials in the United States demon-
strated that, although quality of life is measurably improved for each incre-
mental increase in hemoglobin concentration, the greatest increases are
observed with the treatment of mild as opposed to moderate or severe anemia.
The greatest improvements in quality of life were predicted to occur as hemo-
globin concentration increased from 11 to 12 g/dL [37]. Because quality of life
improvements are observed particularly with the treatment of mild anemia,
where transfusion is infrequently an issue, these observations are potentially
much more important in terms of the number of patients benefited than the
transfusion data.
