Benefits of Erythropoietic Agents May Extend Beyond Improving Fatigue and Quality of Life

DENVER, Colorado-Treating cancer-related anemia improves quality of life and may have other potential therapeutic benefits for cancer patients, according to speakers at a cancer-related anemia symposium presented in conjunction with the 28th Annual Congress of the Oncology Nursing Society. The expert panel also discussed the need for earlier intervention with flexible dosing regimens and outlined potential future applications of erythropoietic agents. Changing Transfusion Guidelines
"Before 1980, red blood cell transfusions were given frequently because there wasn't much worry about transfusions. We would give people transfusions at a hemoglobin level under 10 g/dL," said David H. Henry, MD, clinical associate professor of medicine at the University of Pennsylvania School of Medicine in Philadelphia. In the 1980s, concerns about transfusion-related diseases and the scarce blood supply were responsible for changing transfusion guidelines to 8 g/dL. "Now we're starting to think about early intervention, perhaps under 12 g/dL, and treating up to and including 12 g/dL, as well as the potential therapeutic efficacy in cognitive functioning and possible links to survival," Dr. Henry added. The impact of fatigue on quality of life has been documented. Based on data cited by Dr. Henry, 30% of patients experience daily fatigue, 57% have difficulty in socializing with family and friends because of fatigue, and 75% have to alter their work status because of their fatigue. In 2002, Crawford and colleagues showed that quality of life improves with increasing hemoglobin levels (Figure 1). "When you take hemoglobins from 6 g/dL all the way up to 12 g/dL, quality of life steadily improves," Dr. Henry suggested. The greatest functional improvement occurred among patients at 10 g/dL or higher, and most of the improvement was at 11, 12, and up to 13 g/dL. "Females are supposed to be at 12 g/dL and above, and males are supposed to be at 13.5 g/dL and above, so there must be a reason that nature wants us at that set point," Dr. Henry stated. Erythropoietic Agents
Today, agents such as epoetin alfa(Drug information on epoetin alfa) (Procrit) and darbepoetin alfa(Drug information on darbepoetin alfa) (Aranesp) can reduce the need for transfusions and significantly improve fatigue and quality of life among cancer patients. Approved in 1993, epoetin alfa significantly reduces the need for transfusions, causes a rapid rise in hemoglobin level by about 1 g or more by week 4 (Figure 2), can be titrated for early dose escalation after 4 weeks, and improves quality of life independent of tumor response. Approved in 2002, darbepoetin alfa also reduces the need for transfusions, causes a rise in hemoglobin levels (Figure 3), and improves quality of life in responders. It has a longer half-life than epoetin alfa but less epoetin alfa-receptor binding. Titration can be undertaken after 6 weeks. In addition, therapy may improve tumor response rate, patient survival, and cognitive function. However, Dr. Henry noted that about one-third of patients do not respond to erythropoietic agents, and the reason for this lack of response is unknown. Dosing Issues, Prognostic Significance
Lillian M. Nail, PhD, RN, professor and senior scientist at the Oregon Health and Science University School of Nursing in Portland, explored dosing issues and reviewed research on the effects of epoetin alfa on quality of life, patient response, and treatment outcome. The approved of patients with head and neck cancer (91% of whom were men) who were treated with neoadjuvant chemoradiation followed by surgery. In their secondary analysis, researchers divided the population into three groups. Group 1 consisted of patients with pretreatment hemoglobin levels of at least 14.5 g/dL. These patients did not receive epoetin alfa because it had not been approved. Group 2 included patients with a pretreatment hemoglobin level of less than 14.5 g/dL. These patients received epoetin alfa during all or part of their therapy, whenever their hemoglobin levels dropped below 12.5 g/dL. Group 3 had a pretreatment hemoglobin level of less than 14.5 g/dL but did not receive epoetin alfa because it had not been approved. The 2-year survival for the group with the high pretreatment hemoglobin levels was 81%, compared with 60% for the group with the lower pretreatment hemoglobin levels who did not receive epoetin alfa. Group 2 also had a significantly longer median survival than did group 3, and the 2-year survival for group 2 was 88%. These results suggest that low pretreatment hemoglobin levels are a negative prognostic factor for survival, although a larger prospective trial is needed for firm conclusions about the data, Dr. Barsevick added. Cognitive Benefits
There is also evidence to suggest that epoetin alfa can attenuate or prevent cognitive dysfunction in cancer patients undergoing chemotherapy. "Even at standard doses, adjuvant chemotherapy appears to have distressing effects on some aspects of cognitive functioning, including concentration and memory, as well as attention, speed of information processing, and motor speed," Dr. Barsevick explained. These effects are independent of mood changes or self-reported problems. O'Shaughnessy and colleagues examined the effects of epoetin alfa in breast cancer patients undergoing anthracycline treatment. They found that 18% of patients receiving epoetin alfa experienced improvement in cognitive function before the fourth cycle of chemotherapy, compared with only 2% of the placebo group. Moreover, only 4.5% of the epoetin alfa group experienced deterioration in cognitive function, compared with almost 14.0% of the placebo group. These results demonstrate that for breast cancer patients receiving chemotherapy, treatment with weekly epoetin alfa improved or prevented decline in cognitive function in comparison to a placebo control. Furthermore, epoetin alfa may have a neuroprotective effect, shielding the brain from the negative effects of chemotherapy. Animal studies of induced brain ischemia and preliminary studies of patients suffering acute ischemic stroke also support a direct neuroprotective effect of epoetin alfa, concluded Dr. Barsevick.