Table 1.

Summary of FDA ESA Label Changes: November 2007 to August 2008

Label Change	Impact of Change on Labeled Indication(s)
November 2007
Added text to state that symptoms of anemia, fatigue, quality of life, or patient well-being have not been shown to improve in patients with cancer who are treated with ESAs	ESAs were never approved by the FDA for these indications in cancer patients; the added language was meant to clarify this position
ESAs should not be used in patients with cancer unless they are receiving myelosuppressive chemotherapy	Any use other than this indication, including for “anemia of cancer,” is an off-label indication
ESAs should be discontinued once the patient's chemotherapy course has been completed	ESAs are not indicated beyond active chemotherapy treatment
ESAs caused tumor growth and shortened survival in patients with advanced breast, head and neck, lymphoid, and non–small-cell lung cancer when they received a dose that attempted to achieve a hemoglobin level of 12 g/dL or greater; no clinical data are available to determine whether there is a similar risk of shortened survival or increased tumor growth for patients with cancer who receive an ESA dose that attempts to achieve a hemoglobin level of < 12 g/dL	This statement did not change any indications, but made explicit the lack of prospective, controlled data on survival and tumor progression in patients whose hemoglobin levels are kept < 12 g/dL with ESA use
March 2008
Revised Boxed Warnings and Warnings Section to change “advanced breast cancer” to “breast cancer” and to add “cervical cancer” to the following sentence: ESAs shortened overall survival and/or time-to-tumor progression in clinical studies in patients with breast, non–small-cell lung, head and neck, lymphoid, and cervical cancers when dosed to target a hemoglobin of ≥ 12 g/dL.	This statement did not change any indications, but added non-advanced breast and cervical cancer to the list of malignancies where studies had shown shortened overall survival and/or time to tumor progression when ESAs were dosed to target a hemoglobin > 12 g/dL
August 2008
ESAs are no longer indicated if anticipated treatment outcome is cure	ESAs are no longer indicated in any patient, regardless of receipt of myelosuppressive chemotherapy and subsequent possible anemia, if the anticipated treatment outcome for that patient is cure
	ESAs are still indicated for patients receiving myelosuppressive chemotherapy when the goal of chemotherapy is palliation, not cure
ESAs should not be initiated at hemoglobin levels ≥ 10 g/dL	There is no approved use for beginning ESA therapy in any patient with a hemoglobin of 10 g/dL or higher
Removes “… or exceeds 12 g/dL” as an upper range for ESA use	Clarifies that 12 g/dL is not a goal or upper range for target hemoglobin; rather, the lowest hemoglobin level needed to avoid transfusion should be the goal
Removes language that allowed earlier initiation of ESAs or treatment to higher hemoglobin targets if the patient cannot tolerate anemia because of a comorbid condition	There is no approved use for beginning ESAs in patients with hemoglobin levels ≥ 10 g/dL, despite any comorbid conditions
Boxed Warning no longer focuses on studies with hemoglobin targets > 12 g/dL	This statement did not change any approved uses, but removes the emphasis on results from studies with hemoglobin targets > 12 g/dL

Abbreviations: FDA, Federal Drug Administration; ESA, erythropoeisis-stimulating agents.