NEW YORK-Preliminary data from a pilot study show that use of recombinant human erythropoietin (epoetin alfa, Epogen, Procrit) in breast cancer patients receiving adjuvant chemotherapy increases hemoglobin levels and improves quality of life, especially energy and activity.
NEW YORKPreliminary data from a pilot study show that use of recombinant human erythropoietin (epoetin alfa, Epogen, Procrit) in breast cancer patients receiving adjuvant chemotherapy increases hemoglobin levels and improves quality of life, especially energy and activity.
The study is also examining the effects of epoetin on cognitive function in these women, said Joyce O’Shaughnessy, MD, associate director, US Oncology Research, Baylor-Charles A. Sammons Cancer Center, Dallas. She discussed the data in a presentation at the Chemotherapy Foundation Symposium XIX (abstract 74).
The 100 women in the study are being assessed for cognitive function at baseline just before cycle 4 of chemotherapy and 6 months after treatment ends. Two tests are used to evaluate executive control function, a frontal lobe function that involves multitasking or "putting together simple tasks into a complex sequential behavior," she said.
The EXIT 25 test asks 25 questions to determine executive control function, while CLOX is a simpler tool. The rationale for using both was to determine whether the simpler CLOX could substitute for EXIT 25 in future studies. Quality of life was measured with the FACT-An and the Linear Analog Scale, and mood with the Profile of Mood States.
Dr. O’Shaughnessy noted that past studies of cognitive function in breast cancer patients receiving adjuvant chemotherapy failed to stratify for menopausal and hormone therapy status. This is important, she said, because chemotherapy-induced menopause or estrogen-therapy withdrawal can also lead to impaired memory and concentration.
"We stratified the women by menopausal status as well as whether they had recently stopped hormone replacement therapy," she said. "We really tried to control that variable as best we could."
All patients in the study received four cycles of anthracycline-based chemotherapy. Adriamycin/cyclophosphamide (AC) was the most common chemotherapy regimen in the trial, Dr. O’Shaughnessy said. Adriamycin-taxane regimens were also used. Patients were randomized in a double-blind fashion to receive 40,000 units per week of epoetin given subcutaneously from the beginning of chemotherapy or placebo.
Neuroprotective in Animal Studies
Animal studies have shown that epoetin, a glycoprotein that stimulates red blood cell production, crosses the blood-brain barrier and can have a neuro-protective effect. Rodent brain studies showed that neurons express erythropoietin receptors and that glial cells and astrocytes make erythropoietin.
In animal models, she said, the agent was shown to conserve more brain tissue than saline placebo, and in a mouse study, mice receiving erythropoietin learned how to swim a maze more quickly than those receiving saline.
While the cognitive function assessments at 6 months after therapy have not been completed, Dr. O’Shaughnessy was able to report differences in mean hemoglobin levels for the two cohorts. At all time periods, the levels were higher in patients who received epoetin, she noted. "The final difference between the placebo and epoetin alfa groups," she said, "was 2 g/dL."
Assessments are also showing differences in diminution of energy and decreased activity. "It was quite apparent to those of us who took part in this clinical trial who was getting the epoetin alfa," she said, "not only because their hemoglobin levels stayed up, but also because they felt a great deal better than we’re used to seeing with women who are getting AC chemotherapy."