Adding the erythropoiesis-stimulating agent (ESA) epoetin alfa to the chemotherapy regimen for high-risk breast cancer improved hemoglobin levels for patients, but it also resulted in increased thrombosis, according to a recent study.

Previous research had shown epoetin alfa to be effective in the treatment and prevention of chemotherapy-induced anemia in persons with breast cancer, but some studies indicated an associated increased risk for death and serious adverse events, including thromboembolic events.

The latest investigation, conducted by Volker Moebus, MD, of the Klinikum Frankfort Höchst in Frankfurt, Germany, and colleagues and published in Journal of the National Cancer Institute (2013;105:1018-1026), involved 658 persons with high-risk breast cancer. These patients had been randomized to receive intense dose-dense sequential chemotherapy with epirubicin, paclitaxel, and cyclophosphamide every 2 weeks. Nearly half the group (324 patients) was further randomized to receive epoetin alfa as well.

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Moebus and team found that median baseline hemoglobin levels decreased for both groups over the first three cycles of chemotherapy. However, no decline was seen from baseline to cycle 9 among patients who received epoetin alfa (12.4 g/dL at both cycle 1 and cycle 9). By comparison, the patients who did not receive epoietin alfa exhibited a 2.20 g/dL reduction in hemoglobin from baseline to cycle 9.

In another benefit, fewer epoetin alfa users than control subjects required red blood cell transfusions (12.8% vs 28.1%). However, the incidence of thrombotic events was 7% in the epoetin alfa arm, compared with 3% in the control arm.

After a median follow-up of 62 months, epoetin alfa treatment did not affect overall survival, relapse-free survival, or intramammary relapse.

After approximately 5 years of follow-up, the investigators confirmed that their study showed a beneficial effect of epoetin alfa in the adjuvant treatment of persons with breast cancer who were undergoing intense dose-dense chemotherapy, without deleterious effects on disease progression or mortality.

However, they acknowledged, the study was too small to detect any negative effects on survival between users and nonusers of epoetin alfa, and the results confirmed the known detrimental effects epoetin alfa has on thrombotic complications.

Nevertheless, concluded the authors, “With the exception of this [thrombotic] risk, ESAs appear to be safe drugs for the treatment of chemotherapy-induced anemia or the primary prevention of anemia in patients with [intense dose-dense] chemotherapy regimens.”