Iron Plus Darbepoetin Increases Hemoglobin Levels Better and Faster Than Darbepoetin Alone

Click here to view as PDF.

PHASE II

Previous studies have suggested that 20% to 30% of patients with chemotherapy-induced anemia (CIA) do not benefit from erythropoiesis- stimulating agents (ESAs) because they have functional or absolute iron deficiency anemia. At the 33rd Congress of ESMO in Stockholm, Sweden, Auerbach et al presented findings from a recent study that found administration of intravenous (IV) iron intensified and accelerated cancer patients’ response to darbepoetin alfa (Aranesp).

The trial enrolled 238 patients who underwent chemotherapy for ≥8 weeks for a nonmyeloid malignancy; had a hemoglobin level ≤10 g/dL; and had no deficiency in baseline B₁₂, folate, or iron. Patients were randomized to 1 of 4 groups: one group received darbepoetin 300 mcg plus 400 mg IV iron dextran, another received the same dose of darbepoetin without iron, a third group received darbepoetin 500 mcg with 400 mg IV iron dextran, and a fourth group received the same dose of darbepoetin but without iron. Treatment was administered every 3 weeks, with the percentage of patients to achieve a hemoglobin level of 11 g/dL at 15 weeks as the primary end point. Researchers halted darbepoetin treatment for patients when their hemoglobin level surpassed 13 g/dL, but IV administration of iron was continued.

Data from the 2 iron groups were pooled, and data from the no-iron groups were similarly pooled; 82% of patients who received iron attained primary end point versus 72% of patients not treated with iron. Patients whose therapy included IV iron achieved the target end point at a median of 8 weeks, compared with 10 weeks for those who received darbepoetin alone.

Hematopoietic response, defined as an increase of 2 g/dL in hemoglobin level or achieving a hemoglobin level of ≥12 g/dL from baseline to treatment completion, was 63% in the darbepoetin-only group and 82% for those given darbepoetin plus iron. Michael Auerbach, MD, clinical professor of medicine at Georgetown University, Washington, DC, and lead author of the study, said that “This finding is consistent with results from 5 previous published studies with no contradictory data.” Dr. Auerbach suggested that routinely adding IV iron to ESA treatments in patients with CIA could amount to “a savings of over a billion dollars a year.”

Note that the FDA warns against the use of ESAs “in patients undergoing myelosuppressive therapy when the anticipated outcome is cure.”

Auerbach M, Silberstein P, Webb RT, et al. Darbepoetin alfa 500 mcg or 300 mcg once every three weeks with or without iron in patients with chemotherapyinduced anemia. Paper presented at: 33rd annual meeting of the European Society for Medical Oncology; September 15, 2008; Stockholm, Sweden.