DALLASResponding to a growing body of research that suggests
cognitive dysfunction and asthenia are prevalent side effects of adjuvant
chemotherapy for breast cancer, Joyce O’Shaughnessy, MD, of US Oncology is
investigating recombinant human erythropoietin as a neuroprotective agent.
One hundred women with early stage breast cancer have been
recruited for a randomized trial at US Oncology centers. All are receiving an
anthracycline regimen such as doxorubicin/cyclophosphamide (Cytoxan, Neosar)
during the 4-month pilot study. Half will also receive epoetin alfa (Procrit,
Eprex, Erypo); the other half will receive a placebo.
"Asthenia and cognitive dysfunction may be significant
consequences of adjuvant chemotherapy for breast cancer," explained Dr. O’Shaughnessy,
director of the cancer prevention program and co-director of the breast cancer
research program at Baylor-Charles A. Sammons Cancer Center. The purpose of the
study, she said, is to "determine whether Procrit prevents cognitive
dysfunction and decreases the fatigue associated with adjuvant
Often Goes Undetected
Impaired memory and decreased ability to concentrate appear to
be the most significant cognitive effects in breast cancer patients undergoing
adjuvant chemotherapy, according to Dr. O’Shaughnessy. Yet cognitive
dysfunction often goes undetected, she said, for two reasons.
1. Few physicians evaluate patients for cognitive dysfunction.
2. Depression and menopausal symptoms, both common in breast
cancer patients, can also lead to impaired memory and concentration.
Dr. O’Shaughnessy questioned whether asthenia might be a
manifestation of cognitive dysfunction. Feeling fatigued even at rest, a
hallmark of asthenia, might show "loss of executive control function,
which is the ability to process simple ideas into complex goal-oriented
behavior," she stated.
Dr. O’Shaughnessy cited several published studies that found
breast cancer patients had measurable cognitive impairment after adjuvant
chemotherapy, as compared to a control group. For example, in one trial
reported in the Journal of the National Cancer Institute (90:210-218,
neuropsychological examinations 2 years after completion of adjuvant therapy
found impairment in 32% of patients in a high-dose arm, 17% of patients in a
standard-dose arm, and 9% of patients in a control arm.
Evidence that epoetin might have neuroprotective effects comes
primarily from research with animal models. It has been shown to prevent
glutamate-induced neuronal death in vitro and protect against ischemia-induced
cell death in vivo.
Taken together, these studies "suggest that this peptide
growth factor may have both neuroprotective and cognitive function-enhancing
effects," Dr. O’Shaughnessy summarized.