Iconomou, G., Koutras, A., Karaivazoglou, K., Kalliolas, G.D., Assimakopoulos, K., Argyriou, A.A., . . . & Kalofonos, H.P. (2008). Effect of epoetin alpha therapy on cognitive function in anemic patients with solid tumors undergoing chemotherapy. European Journal of Cancer Care, 17(6), 535–541.

The study's primary aim was to assess whether erythropoietin (epoetin alfa) would improve cognitive performance in a group of patients with cancer who were anemic and receiving chemotherapy. Its secondary aim was to confirm the positive impact of erythropoietin on hematologic parameters and quality of life.

Participants were treated with 40,000 units of erythropoietin weekly for 12 weeks. After the first four weeks of therapy, if the increase in hemoglobulin (Hgb) was less than 1 g/dL over the baseline value, the dose of erythropoietin was increased to 60,000 units weekly. In patients whose Hgb level exceeded 13.0 g/dL, erythropoietin was withheld until Hgb decreased to less than 12.0 g/dL, and resumed at that point to 75% of the previous dose. All participants also received 200 mg of oral elemental iron daily throughout the study. Questionnaires were administered prior to epoetin alfa therapy and at the study's completion.

• The number of participants was 55, with 50 completing the study.
• The average participant age was 58.9 ± 9.9 years.
• 63.6% of the participants were female and 36.4% were male.
• 30.8% of the participants had breast cancer, 21.8% had colorectal cancer, 18.2% had lung cancer, 18.2% had genitourinary cancer, and 11.0% had another form of cancer.
• The average participant years of education attained was 8.7 ± 4.2. 
• The average participant Hgb level was 10.35 ± 0.50 g/dL.

This was a single-site study in Greece.

The study utilized a prospective, longitudinal, single-arm design. 

• The Mini-Mental State Examination (MMSE) measured global cognitive function.
• The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-30 (EORTC QLQ-C30) measured global and functional quality of life using six subscales (global, physical, role, cognitive, emotional, social functioning) and three symptom scales (for fatigue, pain and nausea/vomiting). Scores range from 0–100, with higher scores indicating higher quality of life for the global and functional scales. The Greek version was employed. 

There were no significant differences in cognitive function between erythropoietin responders and non-responders. Sixteen percent of patients had cognitive impairment at baseline measurement (MMSE score < 24). MMSE mean scores increased from 27.24 at baseline to 27.90 at week 12 (p < 0.016). Change in Hgb levels were associated with the magnitude of improvement in quality-of-life parameters such as fatigue (p < 0.01), social function (p < 0.01), and role function (p < 0.01). MMSE changes were not associated with changes in Hgb levels. 

The study failed to demonstrate a clinical benefit of erythropoietin on cognitive function during treatment.

• The study had a small sample size.
• There was no control or comparison group.
• The MMSE is not sensitive enough to detect subtle cognitive changes and has ceiling effects; overall, patients had high baseline scores.
• There was a lack of alternate forms for repeated administration.