O’Shaughnessy, J.A., Vukelja, S.J., Holmes, F.A., Savin, M., Jones, M., Royall, D., . . . & Von Hoff, D. (2005). Feasibility of quantifying the effects of epoetin alpha therapy on cognitive function in women with breast cancer undergoing adjuvant or neoadjuvant chemotherapy. Clinical Breast Cancer, 5(6), 439–446.

The study's primary aim was to evaluate the effects of erythropoietin (epoetin alfa) on cognitive function and mood in patients with breast cancer. Its secondary aim was to evaluate the effects of erythropoietin on fatigue and quality of life of patients with breast cancer.

At the beginning of 4 weeks of chemotherapy, patients were randomly assigned to receive 40,000 units of epoetin alfa subcutaneously once weekly or a placebo, as administered over 12 weeks.

• All participants were female and had breast cancer.
• The number of participants was 94.
• There were 47 participants in the erythropoietin group and 47 in the placebo group.
• The average participant age was 53.3 ± 9.7 years in the erythropoietin group and 54.3 ± 12.0 in the placebo group.
• All participants were scheduled to receive four cycles of anthracycline-based adjuvant or neoadjuvant chemotherapy with or without a taxane.
• All participants had a Karnofsky performance score of ≥ 70% and an estimated life expectancy of ≥ 1 year.

The study took place at 13 sites in the United States.

The study utilized a longitudinal, exploratory, double-blind, randomized, placebo-controlled design.

• The Executive Interview (EXIT-25) measured executive function.
• The Clock Drawing Task (CLOX) measured executive function.
• The Functional Assessment of Cancer Therapy (FACT)-Anemia measured cancer-related quality of life specific to the symptom of anemia.
• The Karnofsky Performance Status scale (KPS) measured general well-being. Scores range from 0 (death) to 100 (perfect health with no complaints or signs of disease).
• Quality of life was measured by a linear analogue scale assessment.
• The Profile of Mood States (POMS) was also utilized. 

Although patients in the treatment arm had a greater improvement in executive function between baseline and after completion of the treatment phase, this difference was not significant. The mean change over time in executive function was similar between the two groups at the six month follow-up assessment.

The study was unable to demonstrate an effect of erythropoietin on executive cognitive functioning.

• The number of doses of erythropoietin given in the treatment group was unclear.
• The authors stated that the CLOX test was found to be an insensitive measure for detecting cognitive changes.
• There was a lack of alternate forms for repeated administration with the EXIT-25 and CLOX tests.
• The results were confounded by chemotherapy treatment variations and the eventual administration of epoetin to the placebo group after the initial treatment phase.