Clinical Assessment and Management of Cancer-Related Fatigue

Although many scales are available, the validity of self-reporting on simple fatigue-rating scales is equal to or better than most complex, lengthy scales [36]. Therefore, unidimensional tools such as the numeric rating scale of 0–10 are commonly used in clinical practice. Mild fatigue (0–3) requires periodic re-evaluation, and moderate and severe fatigue need further evaluation and management [37].

Primary Evaluation

This phase involves a focused history and physical examination and assessment of concurrent symptoms and contributing factors.

History and Physical Examination

A detailed history of the patient’s malignancy and type of previous and current treatment may help reveal the cause of fatigue. New-onset fatigue or increase in fatigue may be related to the progression of disease in patients with active malignancy or recurrence of cancer in survivors. These patients may require appropriate testing to assess the underlying disease pattern. A detailed review of systems may help identify some of the contributing factors, which are discussed below. A detailed history regarding medications, including over-the-counter drugs, complementary agents, and past and prior cancer therapies, is helpful as medications can contribute to fatigue. For example, opioids may cause drowsiness and fatigue, which could be improved by dose adjustments. A focused history of fatigue should be obtained in all patients with moderate to severe CRF, which includes the onset, pattern, duration, associated or alleviating factors, and interference with functioning, including activities of daily living [37]. Physical examination should focus on identifying signs of organ dysfunction and features of substance or alcohol abuse which may cause poor sleep and fatigue.

Assessment of Contributing Factors

The management of fatigue should be multifactorial, with a comprehensive assessment and treatment plan to address all modifiable fatigue etiologies. The Table lists potential contributing factors to fatigue that should be considered when evaluating patients for CRF; several common conditions are discussed below.

Anemia. Anemia has been correlated with fatigue and quality of life. In a study of 4382 cancer patients receiving chemotherapy, quality-of-life measures using FACT-Anemia scores improved with increased hemoglobin levels [38]. Cancer patients may have anemia due to marrow-suppressing effects of chemotherapy and may also have iron deficiency anemia due to blood loss or autoimmune hemolytic anemia. Therefore, a detailed work-up is required to identify the etiology of anemia. Patients with CRF whose anemia is related to chemotherapy or anemia of chronic disease may benefit from red blood cell transfusion or erythropoiesis-stimulating agents (ESAs). ESAs have been studied extensively; however, their use is controversial because of concerns about thromboembolic side effects leading to adverse outcomes [39]. Also, ESA therapy is not recommended in patients with hematologic malignancies. ESA use should be restricted to patients with chemotherapy-related anemia with hemoglobin below 10 mg/dL and should be discontinued in 6 to 8 weeks if patients do not respond [40]. Other patients may benefit from blood transfusions, which were shown to help in patients with hemoglobin levels between 7.5 and 8.5 g/dL [41].

Sleep disturbance. Poor sleep is common in fatigued cancer survivors [42]. Pro-inflammatory cytokines can disrupt the sleep–wake cycle, causing changes in the HPA axis and neuroendocrine system, which in turn may lead to increasing fatigue. Heckler et al showed that improvement in nighttime sleep leads to improvement of fatigue [43]. Cognitive behavioral therapy and sleep hygiene are important in caring for patients with CRF and poor sleep [44]. Taking a warm bath and/or drinking a glass of milk before bedtime, avoiding caffeinated drinks, and avoiding frequent napping in the day might help. Some patients may require medications such as benzodiazepines or non-benzodiazepine hypnotics (eg, zolpidem) to promote sleep [45]. Melatonin agonists are approved for insomnia in the United states, but not in Europe [46].