Massa, E., Madeddu, C., Lusso, M.R., Gramignano, G., & Mantovani, G. (2006). Evaluation of the effectiveness of treatment with erythropoetin on anemia, cognitive functioning and functions studied by comprehensive geriatric assessment in elderly cancer patients with anemia related to cancer chemotherapy. Critical Reviews in Oncology/Hematology, 57(2), 175–182.

The study's primary aim was to examine the relationship of changes in Hgb levels following erythropoietin treatment to changes in cognitive functioning, as studied in older adult patients with cancer undergoing chemotherapy treatment. Its secondary aim was to assess the relationship of changes in Hgb levels following erythropoietin treatment to changes in functions studied in the Comprehensive Geriatric Assessment.

The study's treatment cycle was 12 weeks. For the first 2 weeks, all patients were treated with 10,000 units of erythropoietin twice daily for 6 days a week. For the following 10 weeks, participants were administered 10,000 units of erythropoietin 3 times a week. Participants were also treated with 125 mg of intravenous sodium ferric gluconate complex weekly, or more than once a week if serum iron values were below the inferior limit of normal range. All assessments, including cognition (as based on the MMSE) were completed at baseline prior to treatment with erythropoietin, and at weeks 4, 8, and 12 of treatment.

• The number of participants was 10.
• The average participant age was 71.4, with a range of 68–75.
• 50% of participants were female and 50% were male.
• 40% of participants had non–small-cell lung cancer, 10% had oral cancer, 10% had ovarian cancer, 10% had breast cancer, 10% had endometrial cancer, 10% had colon cancer, and 10% had stomach cancer.
• All participants had an ECOG performance status of 0–2 and an initial MMSE score of 19 or greater. 

The study took place at a single-site location in Italy. 

The study was a prospective single-arm trial.

The Mini-Mental State Examination (MMSE) measured global cognitive function.

The Comprehensive Geriatric Assessment (CGA) is a multidimensional, interdisciplinary diagnostic process that determines the medical, psychological, and functional capabilities of a frail elderly person. It includes

• Activities of Daily Living Scale (ADL). Scores ranging between 0–8 were used to assess functional status for self-care activities.
• Instrumental Activities of Daily Living Scale (IADL). Scores ranging between 0–8 were used to assess functional status for higher-level activities.
• Geriatric Depression Scale (GDS), a 15-item questionnaire.
• The Mini Nutritional Assessment (MNA).

Nine participants (90%) showed significant improvement in cognitive function compared to baseline (p < 0.005), with eight of these patients also responders to erythropoietin in showing correction of anemia. All of these patients maintained improved MMSE scores after weeks 8 and 12 (p = 0.009 and 0.006). There was significant correlation between changes in Hgb levels and cognitive functioning (p = 0.049). There were no significant changes in ADL, IADL, GDS, or MNA scores as compared to baseline scores.

At baseline, the mean Hgb level was 10.3 g/dL, and 40% of patients displayed cognitive impairment (MMSE score < 24). After four weeks of treatment, Hgb levels increased significantly (p < 0.001). 

The study found that treating anemic patients undergoing chemotherapy significantly improved anemia, and that this improvement was correlated with an improvement in cognitive function. However, definitive conclusions cannot be drawn from this study because of multiple limitations.

• The study had a very small sample size for the participants' multiple types of cancer, regimens, and variability in stage of disease.
• The study lacked a control group as a comparison.
• All patients were anemic at baseline.
• The MMSE is not sensitive enough to detect subtle cognitive changes.
• There was a lack of alternate forms for repeated administration of MMSE, so practice effects may have influenced study outcomes.
• The study followed an atypical erythropoietin dosing schedule.