Anemia, a frequent complication of cancer, is also induced or exacerbated by chemotherapy. Generally defined as a hemoglobin concentration of < 12 g/dL, anemia is estimated to affect about 50% of cancer patients. The incidence of anemia can, however, vary substantially depending on tumor type, extent of disease, and whether the patient is receiving myelosuppressive therapy.
Anemia is associated with many symptoms, including exhaustion, weakness, impaired concentration, dyspnea, respiratory distress, lethargy, and fatigue. Fatigue is the symptom generally identified as the most significant contributory factor to poor quality of life in patients with cancer.[3-7] In addition, some studies suggest that anemia may reduce the efficacy of anticancer therapy.[8-12] An association between anemia and poorer therapeutic outcome and survival following radiotherapy and/or chemotherapy has been documented in patients with some malignancies.[8,9,11,13]
The etiology of anemia in the oncology setting is multifactorial. The release of cytokines in response to the inflammatory or neoplastic process reduces the erythrocyte lifespan and impairs erythroid colony formation, erythropoietin(Drug information on erythropoietin) production, and iron reutilization. Anemia may also be induced by acute and chronic blood loss, particularly among patients with gastrointestinal, head and neck, genitourinary, and uterine cancers.[2,14] Other factors, such as replacement of active bone marrow in advanced metastatic carcinoma or hematologic malignancies, may destroy progenitor cells, induce fibrotic or fatty replacement, and contribute to anemia.
Both chemotherapy and radiotherapy can induce or further exacerbate anemia by suppressing erythropoiesis.[2,14] In addition, chemotherapy can reduce erythropoietin production by direct effects on the renal tubules, decrease the sensitivity of the hematopoietic system to erythropoietin, and cause stem cell damage, or destroy mature hematopoietic cells. Chemotherapy may also lead to long-term myelodysplasia or microangiopathy. Radiotherapy may damage bone marrow stem cells, and lead to transient or sustained anemia as these cells have a limited capacity to repair such damage.
Until recently, anemia that was not severe or life-threatening was considered of little consequence and was frequently untreated. However, increasing recognition that the treatment of mild-to-moderate anemia can yield clinically significant improvements in patient health-related quality of life has resulted in advances in the palliative management of cancer. The statistically significant correlation of hemoglobin increase and improved quality of life, independent of the tumor response to therapy, clearly demonstrates the impact of improving hemoglobin levels in anemic patients with cancer.[6,15,16]
Current treatment options for patients with anemia and malignant disease include red blood cell transfusions, iron supplementation for iron deficiency, or erythropoietic agents, including epoetin alfa (Epogen, Procrit) and darbepoetin alfa(Drug information on darbepoetin alfa) (Aranesp).[2,17] Red blood cell transfusions provide an immediate benefit in the case of life-threatening or severe symptomatic anemia, but are associated with inherent risks and inconvenience. Although associated with a slower onset of efficacy, erythropoietic agents are safer than transfusion, and are effective and widely used to treat chemotherapy-induced anemia.
Recombinant human erythropoietin (rHuEPO) was initially studied in anemic cancer patients receiving chemotherapy based on the observation that endogenous erythropoietin concentrations are inadequate for the degree of anemia, and that the administration of chemotherapy may blunt the erythropoietin response to anemia. In one of the first published reports of rHuEPO treatment in anemic cancer patients receiving chemotherapy, Henry and Abels reported results from a series of large, placebo-controlled trials in which rHuEPO was administered at 150 U/kg three times per week for 12 weeks, with dose increases permitted after 8 weeks. The results showed that rHuEPO therapy could alleviate the need for blood transfusions in anemic cancer patients receiving chemotherapy (combined platinum- and nonplatinum-based chemotherapy groups) in the second and third month of therapy. In addition, a statistically significant increase in hemoglobin concentration relative to placebo both in patients receiving non-cisplatin-based chemotherapy as well as in patients receiving cisplatin(Drug information on cisplatin)-based chemotherapy was observed, with 58% and 48% of patients, respectively, achieving a 6-point hematocrit increase from baseline in the absence of a transfusion.
Numerous controlled and uncontrolled studies, including several large US community-based studies, have confirmed these findings. In a study of over 2,000 anemic patients with nonmyeloid malignancies receiving chemotherapy treated with