EVANSTON, Illinois-Anemia is the most treatable cause of fatigue in cancer patients and aggressively managing anemia could significantly improve the quality of life of cancer patients and may also impact survival, according to David Cella, PhD. Anemia has been associated with poor prognosis and increased mortality among cancer patients, although a causal relationship has not yet been established, he noted.
EVANSTON, IllinoisAnemia is the most treatable cause of fatigue in cancer patients and aggressively managing anemia could significantly improve the quality of life of cancer patients and may also impact survival, according to David Cella, PhD. Anemia has been associated with poor prognosis and increased mortality among cancer patients, although a causal relationship has not yet been established, he noted.
Dr. Cella is Director of the Center on Outcomes Research and Education at Evanston Northwestern Healthcare and professor of psychiatry and behavioral science at Northwestern University School of Medicine in Evanston, Illinois.
Targets of Therapy
Hemoglobin is the major target of erythropoietic therapy and available data show that such therapy is effective in raising hemoglobin levels. Hemoglobin would be the bull’s eye in an erythropoietic therapy outcomes target. As you go outside the center, outcome targets such as fatigue, physical functioning, mood and general well-being are impacted to a lesser extent (see Figure 1).
Symptoms of Anemia
At hemoglobin levels of less than 8 g/dL, anemia is severe with "markedly reduced exercise capacity, difficulty breathing even at rest, rapid or irregular heartbeat at rest, an increased risk of angina, myocardial infarction, and transient ischemic events. This is the point where most people would clearly have a transfusion trigger," Dr. Cella said. A transfusion can achieve an immediate turnaround, while erythropoietic therapy might be used when time is not so crucial.
"Anemia," Dr. Cella said will directly reduce your activity level, require more rest, reduce your productivity, probably reduce your cognitive efficiency either directly or indirectly, and lead to a general functional decline. That in turn, if not reversed and if it becomes chronic, can lead to reduced self-esteem, compromised social roles in relationships, and even place patients at risk for depression and withdrawal."
Studies show that 80% of patients with cancer will experience significant fatigue at some point in time. Between 60% and 100% of cancer patients being treated with radiation and chemotherapy experience fatigue. "It is also very common after surgery or treatment with biologic response modifiers. Fatigue is associated with the disease itself and other comorbid conditions, so it is not only related to anemia," Dr. Cella said. "It gets worse as people’s disease gets worse. It also ties in with depression, cachexia, pain, and insomnia."
Clinical Trials With Erythropoietic Therapy
A pivotal phase III randomized, controlled European trial in lung cancer patients showed that darbepoetin alfa (Aranesp) reduced the need for transfusions (see Figure 2).
In addition, patients receiving darbepoetin alfa reported greater decreases in fatigue than those receiving placebo (see Figure 3).
Several other studies have demonstrated that human recombinant erythropoietin also reduces the need for transfusion, increases hemoglobin, and ameliorates fatigue, thereby improving quality of life, Dr. Cella noted. These studies were reviewed using quality-of-life measurements to interpret the results.
Changes of 10 or more points on the Functional Assessment of Cancer Therapy indicate that patients have reported significant increases in activity levels and the ability to do work, better energy and better performance status. In a randomized placebo-controlled study, Littlewood and associates found that patients treated with erythropoietin alfa reported positive changes on several FACT measures, including those for anemia and fatigue. The FACT scores for the placebo group worsened by nearly the same magnitude. "So it’s not just the benefit of the erythropoietin but also the inexorable decline that one sees in solid tumor oncology in this group of patients," Dr. Cella commented.
"Taken alone you wouldn’t see clinical meaningfulness of one group or the other. But taken together, comparing the peak of the treatment group to the trough of the placebo group, you see change scores that are above the threshold of what we consider to be clinically meaningful."