Biology Reference
In-Depth Information
Erythropoietic therapy in the practice of oncology
John Glaspy
Division of Hematology/Oncology, UCLA School of Medicine, 200 UCLA Medical Plaza, Suite 202,
Los Angeles, California 90095-6956, USA
Introduction
It is well recognized that patients with cancer are frequently anemic [1]. The
basic underpinning is the anemia of chronic disease (ACD), with its associat-
ed reduction in endogenous erythropoietin (EPO) concentrations [2]; cytokine-
induced suppression of bone marrow function; disturbances in ferrokinetics,
including both decreased gastrointestinal absorption and increased reticuloen-
dothelial retention of iron; and decreased red cell survival [3]. In addition,
patients with cancer are often subject to other important contributing factors,
including myelosuppressive chemotherapy, radiotherapy, bleeding, hemolysis,
bone marrow tumor infiltration, and poor nutrition. It is not surprising that the
reported frequency of severe anemia (hemoglobin concentration <8 g/dL
and/or red cell transfusion dependence) across a broad spectrum of cancers
and treatment regimens is 5% to 20%, and of mild anemia (hemoglobin con-
centration 8-11 g/dL) is 25% to 45% [1]. Before the introduction into the clin-
ical practice of oncology of recombinant human erythropoietin (rHuEPO) in
1991, the only available treatment for anemia was red blood transfusion, with
all of its inherent disadvantages. Based upon a desire to limit risk to patients
and protect the blood supply,physicians were trained to overlook mild and
moderate anemia and to transfuse only in response to relatively severe, poten-
tially life-threatening symptoms. Implied in this approach was the assumption
that less-profound levels of anemia were clinically insignificant and relatively
asymptomatic. Over the last five years, significant changes have occurred in
our understanding of the impact of anemia on patients with cancer and previ-
ously held beliefs have been challenged or disproven. To a significant extent,
this discovery process has paralleled the earlier experience of nephrologists
treating patients with chronic renal failure and it is likely that we have more to
learn from these colleagues, especially regarding the use of iron in rHuEPO-
treated patients and the role of physicians in advocating for standards of excel-
lence in patient care. (See Chapter 9 for further information.)
Worldwide, several erythropoietic agents are currently available for the
treatment of anemia in oncology practice. (See Chapter 15 for further infor-
mation.) Two forms of rHuEPOs, epoetin alfa and epoetin beta, are in clinical
