Fatigue (PDQ®): Supportive care - Health Professional Information [NCI] - Intervention
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 caused by 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) caused by 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.[15,16] ESAs should be discontinued if there is no response after 6 to 8 weeks (<1-2 g/dL increase in hemoglobin or no 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.
A Cochrane review concluded that ESAs provide a clinically significant reduction in fatigue for anemic patients receiving chemotherapy. However, on the basis of safety concerns raised by the FDA and in view of identified side effects, this review further concluded that ESAs should not be used in clinical practice for fatigue. Clinicians initiate discussions with patients and family members about the risks and benefits of ESAs.