LOS ANGELES—Many, if not most, oncologists agree that erythropoietic therapy can lower the need for transfusions and improve quality-of-life. This is especially true when cancer patients who suffer from fatigue have their hemoglobin levels raised from 10 g/dL or less to 12 g/dL or more. Why then are less than 30% of patients who should receive erythropoietic therapy being treated with it? (See Table 1.)

There are several reasons for this (if reimbursement were not an issue), according to John A. Glaspy, MD, MPH, of the University of California School of Medicine in Los Angeles.

• The significant numbers of non-responders blunt enthusiasm for erythropoietic therapy in the oncology community and weaken its cost-effectiveness as a treatment strategy.
• Physicians may not be receptive to quality of life as an endpoint.
• Erythropoietic therapy has not always been easy to administer.

Recombinant human erythropoietin(Drug information on erythropoietin) (rHuEPO) is made up of several isoforms that differ in the number of glycosylation sites and sialic acids present, from 9 to 14. The greater the number of sialic acid molecules present in an isomer, the greater the potency of the agent in vivo (see Figure 1).

"That led to an effort that spanned years, through site-directed mutagenesis, to develop new erythropoietin genes that added glycosilation sites," Dr. Glaspy explained. "That search ended in darbepoetin alfa (Aranesp), which has two additional glycosylation sites and up to eight additional sialic acids (see Figure 2). So instead of a maximum of 14, there are a maximum number of 22 that are added to the protein." Compared to rHuEPO, darbepoetin alfa(Drug information on darbepoetin alfa) is more potent in vivo.

Defining Terms

Meaningful comparison of study results requires agreement on how outcomes are defined.

Hemoglobin response is defined as a hemoglobin increase greater than 2 g/dL (from baseline) in the absence of red blood cell transfusions within the preceding 28 days. But what about a baseline hemoglobin of 11 that rose to 12? Although that gain would put the hemoglobin at a normal level, it didn’t fit the definition of a hemoglobin response because the hemoglobin level only rose 1 g/dL. That change is classified as a hemoglobin correction, defined as hemoglobin greater than 12 g/dL in the absence of red blood cell transfusions within the preceding 28 days. Together, the hemoglobin response and the hemoglobin correction can be used to calculate the hematopoietic response, defined as a hemoglobin increase greater than 2 g/dL (from baseline) or hemoglobin greater than or equal to 12 g/dL. The mean change in hemoglobin refers to the mean change from baseline, in the absence of any red blood cell transfusion within the previous 28 days.