Fatigue (PDQ®): Supportive care - Health Professional Information [NCI] - Intervention
Table 2. Centrally Acting Stimulants for Adult Cancer Patients continued...
Treatment of Anemia
Anemia in patients with cancer is best managed by treatment of the underlying cause. When the cause is obscure or there is no specific remedy, then treatment is supportive. Nutritional interventions, including the intake of nutrient-rich foods and supplements should be considered in addition to other treatment modalities. Transfusion of packed red blood cells is the most widely used and most rapid way to alleviate symptoms in cancer patients with symptomatic anemia. The likelihood of success in raising the level of hemoglobin is very high with transfusion, and the risks of complications are low. Nevertheless, repeated transfusions can be cumbersome, and the risks of blood-borne infection can be worrisome for patients. Other risks include an acute transfusion reaction, transfusion-associated graft-versus-host disease, subtle immune modulation that occurs with transfusion, and iron overload for those with repeated transfusions.
Several large, community-based studies have examined the effectiveness of epoetin alfa and darbepoetin alfa [Level of evidence: I];[Level of evidence: I] in the treatment of cancer-related anemia in patients undergoing chemotherapy.[Level of evidence: II];[Level of evidence: III];[Level of evidence: I] A few of the studies of epoetin alfa employed an open-label, nonrandomized design and included objective endpoints (hemoglobin response, transfusion requirements) and subjective evaluation of fatigue and quality of life. In this setting, epoetin alfa has been effective at increasing hemoglobin levels and decreasing transfusion requirements. In addition, epoetin alfa was associated with improvement in functional status and quality of life, independent of tumor response. Several studies of epoetin alfa and darbepoetin alfa employed a randomized, controlled design. These studies varied in terms of dosing and frequency of medication administration. A review and meta-analysis of randomized and open-label studies concluded that these agents are effective in the management of CRF  but also raises serious concerns about safety data and adverse outcomes associated with these agents. The review concludes that these agents should not be used for the treatment of fatigue in patients with cancer. The authors argue that the risks associated with these agents outweigh their benefits for the treatment of CRF.
The FDA has conducted a comprehensive review of safety information from studies of these agents. The review showed that in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers, erythropoiesis-stimulating agents (ESAs) shortened overall survival and/or increased the risk of tumor progression or recurrence. The review also showed that ESAs increase the risk of serious cardiovascular and thromboembolic events when they are administered to target higher hemoglobin levels (13.5–14 g/dL).
On the basis of these findings, the FDA mandated revised ESA labeling to include an updated warning, a new boxed warning, and modifications to the indications and dosing instructions. The boxed warning includes information on the higher mortality risks due to cardiovascular/thromboembolic events and tumor progression or recurrence. The 2010 American Society of Clinical Oncology (ASCO)/American Society of Hematology (ASH) guidelines recommend the following:
- In accordance with the FDA-approved label, the use of these agents should be restricted to the treatment of anemia (hemoglobin level <10 g/dL) due to concomitant palliative myelosuppressive chemotherapy and should be discontinued upon completion of a course of chemotherapy. (The above does not hold for low-risk myelodysplastic syndrome.)
- In accordance with the FDA-approved label, the lowest possible dose should be used, with the goal of avoiding red blood cell transfusions, because the higher doses increase the risk of cardiovascular and thromboembolic events.
- Initial dose and modification should follow FDA-approved labeling.[26,27] ESAs should be discontinued if there is no response after 6 to 8 weeks (<1–2 g/dL increase in hemoglobin or decrease in transfusion requirements).
- The FDA-approved label states that ESAs are not indicated for patients receiving curative myelosuppressive chemotherapy. However, the 2010 ASCO/ASH recommendations state that clinical judgment, goals of therapy, and patient preference should guide ESA use in the curative and palliative settings.