Biology Reference
In-Depth Information
(see Chapter 2), the anemia of renal failure has been successfully treated with
rHuEPO [51, 52]. In fact, rHuEPO represents a routine treatment for patients
receiving regular hemodialysis or peritoneal dialysis and for many patients not
receiving dialysis (i.e., predialysis patients) [53, 54]. Biologically, this use rep-
resents a form of hormone replacement therapy,although the benefits to the
patient extend beyond the reduced need for transfusions and the associated
risks of iron overload, incompatibility reactions, and viral infections and
include the benefits of increased exercise tolerance, cognitive and psychomo-
tor changes, and relief from hyperdynamic cardiac states. In total, these
changes produce a significant impact on the quality of life of patients [55].
Beyond the surprisingly wide ramifications of correction of anemia in these
patients, the biologic basis for rHuEPO therapy in patients with renal disease
remains replacement of a hormone deficiency secondary to failure of the organ
that produces the hormone. Other uses for rHuEPO, for instance in anemia of
cancer, anemia of chronic disorders, or in chronic heart failure, have lead to
extensive use outside the dialysis clinic.
Anemia in oncology
Anemia in patients with cancer results from a complex interaction of various
factors that make treatment somewhat less predictable than the hormone
replacement-like use in renal failure states. Included in the list of contributing
factors are hemodilution, bleeding, hypersplenism (and hemophagocytosis),
hemolysis, nutritional deficiencies, marrow damage, chemotherapy and radio-
therapy, and the anemia of cancer itself (included in the broader classification
of anemia of chronic disorders [ACD]) [56-59].
Addressing any one of these factors alone represents a significant challenge,
yet the perceived benefits of managing anemia in patients with cancer has led
to a number of successful therapeutic strategies. Perhaps the most obvious
rationale for rHuEPO use in anemic cancer patients is in patients with docu-
mented low endogenous serum EPO concentrations. Concentrations of
endogenous EPO are inherently variable and use of the data is further con-
founded by a phenomenon widely documented in ACD where the absolute
EPO concentration is within the normal range and is low only when consid-
ered relative to the degree of anemia - the so-called “blunted” EPO production
[60]. For the most part, studies of endogenous EPO concentrations in animals
have not illustrated principles to be applied to clinical practice. For instance,
inappropriately low EPO concentrations in tumor-bearing mice did not con-
firm the earlier observations made in tumor-bearing rats [61, 62]. Later work,
however, showed that endogenous EPO concentrations were predictable and
consistent with the degree of anemia [63]. In addition, the effects of
chemotherapy on endogenous EPO concentrations have been variously report-
ed to increase, decrease, or remain unchanged [64-66].
Patients with cancer frequently have circulating endogenous EPO amounts
that are lower than would be expected for the degree of anemia. In early stud-
ies in patients with cancer, inappropriately low endogenous EPO concentra-
