At the 28th Annual Congress of the Oncology Nursing Society, many presentations addressed fatigue and anemia. Topics presented included impact on patient and caregiver quality of life, risk factors, and the role of Aranesp® (darbepoetin alfa) in symptom management.

Fatigue and the Cancer Patient

Approximately 75% of patients undergoing cancer therapy suffer from fatigue, with anemia being a common underlying etiology. Sixty-one percent of patients believe that fatigue affects their ability to work ¹ and recent research indicates that fatigue plays a very important role in the cancer patient's overall quality of life (QOL). ² Furthermore, research suggests that fatigue, as well as pain and sleep disturbances, affect cancer treatment outcomes. ³ Therefore, researchers continue to investigate possible causes of fatigue and potential therapeutic interventions that may lessen its severity.

Results presented from patient questionnaires emphasized the degree to which fatigue negatively impacts patient QOL. In a clinical study involving breast cancer patients who received adjuvant therapy, higher levels of fatigue were associated with reduced mental functioning, social functioning, physical functioning, vitality, general health, and increased pain. ⁴ In this group of women, fatigue was also correlated with an impact on mood and symptoms. ⁵

Researchers evaluating data collected from patients in several studies have identified risk factors that tend to increase the severity and/or incidence of fatigue. The most common of these include low quality sleep, night awakenings, higher number of symptoms from therapy, sleep latency, anxiety, depression, and low physical functioning status. ^6,3 By understanding the impact that these risk factors have on fatigue, nurses and caregivers can take appropriate measures to lessen the severity of fatigue and improve QOL for their patients.

Energy conservation and activity management (ECAM) is an approach that was proposed to help alleviate fatigue. ECAM includes delegating tasks, priority setting, pacing oneself, and planning activities at times of peak energy. In a study involving approximately 400 cancer patients, ECAM was beneficial in decreasing fatigue and distress, as well as decreasing the impact of these symptoms on daily life. Patients who were treated with chemotherapy alone experienced the most improvement of fatigue symptoms from ECAM. ⁷

Another approach to lessening the impact of fatigue is to treat or prevent the common underlying cause, anemia. Prevention and/or early intervention of anemia with an erythropoiesis-stimulating agent versus treatment of anemia once it has occurred will help resolve the issue of fatigue for many patients.

Anemia

Anemia is defined as a hemoglobin (Hb) count of less than 11.5 g/dL. 8 Anemia occurs in 20% to 60% of cancer patients and is most commonly associated with cancers of the lung, breast, ovary, head and neck, and non-Hodgkin’s lymphoma.

The effects of anemia on a cancer patient may be extensive. Anemia can cause fatigue, cognitive dysfunction, decreased QOL, and result in dose reductions or delays in chemotherapy and lower overall treatment intensity. Patient compliance with treatment may also be affected by anemia because treatment becomes less tolerable for the anemic patient, resulting in the delivery of suboptimal regimens. In addition, tumor hypoxia caused by anemia may restrict the effectiveness of oxygen-dependent treatment modalities, such as radiation and some chemotherapy agents. Furthermore, some studies have indicated that tissue hypoxia may promote metastatic properties. ^9,10

Since the maturation of red blood cells from stem cells takes approximately 24 days, treatment for anemia is not immediately effective. Therefore, current clinical efforts are focusing on the prevention and early intervention rather than treatment after anemia has occurred. Caregivers should perform an initial assessment for risk factors and be especially alert to the symptoms in patients with one or more risk factors. These patients are then candidates for early intervention treatment.

Risk factors for developing anemia:

• Elderly patients
• Presence of comorbid conditions
• Type of cancer, especially lung, breast, ovary, head and neck, and non-Hodgkin’s lymphoma
• Advanced stage of cancer
• Prior treatment
• Treatment regimen that includes paclitaxel, carboplatin, cisplatin, topotecan, or CHOP

The current guidelines of ASH-ASCO for evidence-based clinical practice in anemia are as follows: 

• Erythropoiesis-stimulating therapy for Hb<10 g/dL
• Erythropoiesis-stimulating therapy for Hb<12 g/dL if clinically indicated

The current guidelines of the National Comprehensive Cancer Network (NCCN) for anemia recommend intervention when Hb is less than 11 g/dL, in order to increase Hb to at least 12 g/dL.

In order to prevent or treat anemia with early intervention, caregivers need to focus on trends versus single-day measurements of hemoglobin/hematocrit. Changes in a patient’s function and symptoms may be indicative of the onset of anemia. ¹

Aranesp®

Aranesp® (darbepoetin alfa) is a long-acting erythropoiesis-stimulating agent. It was approved by the FDA in 2002 for the treatment of anemia in patients receiving concomitant chemotherapy for nonmyeloid malignancies. Compared with epoetin alfa, Aranesp® has 2 additional N-linked carbohydrate chains that allow for the addition of up to eight sialic acid molecules from 14 to 22. ¹¹ Although receptor-binding affinity decreases with the increased carbohydrate content of Aranesp®, serum half-life increases and in vivo activity increases compared to epoietin alfa. The recommended dosing regimen on the package insert of Aranesp® is 2.25 mcg/kg/wk as a subcutaneous (SC) injection. The minimally effective dose for reduction in number of RBC transfusions is 1.5 mcg/kg. However, the current practice dosing for Aranesp® tends to be 200 mcg/kg SC every other week.

Clinical trials with Aranesp® are ongoing to establish optimal dosing and timing in treatment cycles so that anemia may be treated early or prevented altogether. Inclusion of Aranesp® into ASCO/ASH/NCCN guidelines is expected in the future as results from clinical trials mature. ¹

The decreased dosing requirements for Aranesp® compared with Procrit® (epoetin alfa) may have an impact on QOL as frequent medical visits have been reported to negatively impact both patient and caregiver QOL. Many patients with cancer have frequent medical visits for treatment and/or follow-up. Medical visits often involve a significant portion of time during the day, require help from a caregiver, transportation, and require mobility and energy exertion. Since a significant proportion of these patients are plagued with fatigue, nausea, pain and/or other cancer or treatment-related disabilities, researchers conducted a study to evaluate how frequent medical visits may impact cancer patients and their caregivers. Informal interviews with over 50 cancer patients and their caregivers from West Clinic in Memphis, TN indicated that clinic visits negatively affect patients and caregivers and have a significant impact on their lives. Most patients accepted frequent medical visits as necessary for treatment and a part of their life. However, the factors related to medical visits that had the greatest negative impact included:

• The need to take time off from work
• The need to cancel or change social obligations or engagements
• The inability to finish household and other responsibilities due to time limitations
• Expended energy
  

Patients with anemia reported that frequent medical visits were a burden to their energy because of already significantly reduced energy levels. Costs of transportation were also reported to be a financial burden. Furthermore, clinical visits were associated with feelings of anxiety and sadness as patients were reminded of their disease. Based on these findings, it appears important to try and minimize the frequency of clinical visits for patients and allow them to return to as normal a life as possible. ¹² The number of clinical visits may be reduced with the use of Aranesp®, which requires less frequent dosing while maintaining effectiveness in the treatment of anemia.

As previously mentioned, fatigue can greatly impact a patient’s QOL. A clinical trial conducted by researchers at the Pacific Shores Medical Group evaluated the impact of Aranesp® and Procrit® on QOL in the treatment of anemia-related fatigue. The trial involved over 600 patients with anemia (Hb<11 g/dL) who were receiving chemotherapy. Patients were treated with Aranesp®, Procrit®, or placebo. Patients treated with Aranesp® received significantly less frequent dosing than those treated with Procrit®. Patients treated with Aranesp® or Procrit® who had an increase in Hb of 2g/dL or greater reported a significant improvement in fatigue compared to patients with a change in Hb of 2g/dL or less. Furthermore, patients who reported a significant improvement in fatigue had a significant reduction in depression and anxiety. Conversely, patients who did not report a significant change in fatigue had increased depression and anxiety. Clinical improvements in fatigue were also associated with improved emotional well being and overall health scores. ¹³

Conclusion

Anemia and fatigue are associated with a considerable impact on quality of life as well as physical outcomes in patients with cancer. As caregivers, it is important to try to focus on prevention or early intervention of anemia and/or fatigue to ensure a high QOL. As more clinical evidence regarding anemia emerges, more information defining risk assessments and prevention will become available. Less frequent dosing with Aranesp® for treatment/prevention can reduce the burden on both patients and caregivers and potentially lead to a greater QOL. Clinical trials are ongoing to evaluate Aranesp® dosing at 2, 3, and 4 week intervals. If dosing can be linked to patients scheduled treatment visits, anemia and fatigue can be effectively managed and the frequency of patient and caregiver visits reduced.

References

1. Symposium at 2003 annual meeting of the Oncology Nursing Society. Are Oncology Nurses the Strongest Link? Effective management of chemotherapy-associated neuropathy, anemia, and neutropenia. Gillespie, T. presenter of anemia section. May 1, 2003.

2. Cella D, Peterman A, Passik S, et al. Progress toward guidelines for the management of fatigue. Oncology. 1998. 369-377.

3. West C, Paul S, Miaskowkski C, et al. Symptom clusters predict fatigue severity in oncology outpatients. Proceedings from the 2003 annual meeting of the Oncology Nursing Society. Abstract #136.

4. Byar K, Berger A. Women receiving adjuvant chemotherapy for breast cancer: impact on quality of life and fatigue. Proceedings from the 2003 annual meeting of the Oncology Nursing Society. Abstract #142.

5. Dean G, Sama L, Grant M. Factors associated with fatigue in women before and after surgery for breast cancer. Proceedings from the 2003 annual meeting of the Oncology Nursing Society. Abstract #139.

6. Berger A, Piper B, Higginbotham P. Factors influencing fatigue during and after chemotherapy: results of a feasibility sleep intervention study. Proceedings from the 2003 annual meeting of the Oncology Nursing Society. Abstract #140.

7. Barsevick A, Dudley W, Nail L, et al. Who benefits from energy conservation for cancer-related fatigue? Proceedings from the 2003 annual meeting of the Oncology Nursing Society. Abstract #138.

8. NCCN Guidelines. Available at: http://www.nccn.org/patient_gls/asp/ASP_Script_showTree/SVGAframeset.asp?pg=fatigueidchart=6bkg=. Accessed May 10, 2003.

9.Glaspy J. Clin Oncol Updates. 2001.4:1-13.

10. Subarksy P, Hill R. The hypoxic tumour microenvironment and metastatic progression. Clin Exp Metastasis. 2003.20:237-250.

11. Egrie J, Browne J. Development and characterization of darbepoetin alfa. Oncology (Huntingt). 2002;16:13-22.

12. Moore K, Former B. The impact of medical visits on patients with cancer. Proceedings from the 2003 annual meeting of the Oncology Nursing Society. Abstract #73.

13. Amorajabi M, Tchekmedyian S, Kallich J. Patient-reported depression and anxiety in patients with cancer improves following reduction in anemia-related fatigue with darbepoetin alfa therapy. Proceedings from the 2003 annual meeting of the Oncology Nursing Society. Abstract # 118.