Summary and Introduction
Summary
For cancer patients, anemia can be a debilitating problem that negatively influences their overall quality of life and worsens their prognosis. The condition is caused either by the cancer itself or by cytotoxic treatment. Anemia is the primary indication for transfusion of red blood cells, but the development of recombinant human erythropoietins (epoetins) provides an alternative to red blood cell transfusions. Treatment with epoetins has been shown to reduce transfusion rates and increase hemoglobin response. There is some evidence that epoetins improve quality of life. It remains unclear, however, whether erythropoietin affects tumor growth and survival, and this area requires further investigation. Data from clinical trials suggest that erythropoietin increases the risk of thromboembolic complications. In the management of anemic patients, physicians should follow closely the dosing recommendations in products' package inserts or the ASCO/American Society of Hematology guidelines. Treatment of patients beyond the correction of anemia, however, has to be regarded as experimental and is potentially harmful, so should only be conducted in clinical trials.
Introduction
Anemia is defined as a deficiency in red blood cells (RBCs) and is a widely prevalent complication among cancer patients. The prevalence of anemia varies according to the type of neoplasia. About 50% of patients with solid tumors present with anemia at diagnosis. Hematologic malignancies increase the likelihood of developing anemia; for example, 60-70% of patients with non-Hodgkin's lymphoma are anemic at the time of diagnosis. The National Cancer Institute suggested a classification for anemia based on hemoglobin (Hb) values ( Table 1 ).
The pathophysiology of tumor anemia is multifactorial (Figure 1). Tumor-associated factors such as tumor bleeding, hemolysis, and deficiency in folic acid and vitamin B12, can be acute or chronic. In the advanced stages of hematologic malignancies, bone marrow involvement often leads to progressive anemia. In addition, interaction between tumor cell populations and the immune system can lead to the release of cytokines, especially interferon-γ, interleukin-1 and tumor-necrosis factor-α. This release disrupts endogenous erythropoietin synthesis in the kidney and suppresses differentiation of erythroid precursor cells in the bone marrow. As a result, patients with tumor anemia can have relatively low levels of erythropoietin for the grade of anemia observed. Moreover, activation of macrophages can lead to a shorter erythrocyte half-life and a decrease in iron utilization. Cytostatic therapy and radiation further aggravates anemia in cancer patients. Platinum-based chemotherapy regimens might diminish endogenous erythropoietin production by damaging renal tubular cells, and myelotoxic anticancer drugs can compromise erythroid precursor cells. As a consequence, dose-intensified treatment regimens or shortened treatment intervals, as well as multimodal therapies, are associated with a higher degree of anemia. Mild or moderate (grade 1 and 2) anemia in patients with solid cancers could affect about 60% of patients after platinum-based chemotherapy. Severe (grade 3) anemia in elderly patients with hematologic malignancies can occur in up to 74% of patients with non-Hodgkin's lymphoma after standard CHOP (cyclophosphamide/doxorubicin/vincristine/prednisolone) treatment. In addition, some of the newer chemotherapeutic agents, such as taxanes or vinorelbine, are strongly myelosuppressive and can cause high degrees of anemia.
(Enlarge Image)
Figure 1.
Pathophysiology of anemia. BFU-E, erythropoietic burst formation; CFU-E, erythrocytic colony formation; EPO, erythropoietin; HIF-1, hypoxia-inducible factor-1; IFN-α,β, interferon-α,β IFN-γ, interferon-γ; IL-1, interleukin-1; TNF, tumor-necrosis factor. Figure modified with permission from reference 86 © (1996) Marcel Dekker).