Cancer-related Fatigue

Prevalence, Assessment and Treatment Strategies

Joachim Weis


Expert Rev Pharmacoeconomics Outcomes Res. 2011;11(4):441-446. 

In This Article

Treatment of CRF

Treatment strategies should be designed taking the clinical status of the patient (patient currently under treatment; patients after treatment, but undergoing antihormonal medication; or patients with progressive disease at the end of life) into account.[101,43] Beyond specificities for those subgroups, the following treatment options for CRF are discussed and must be adapted to the individual's needs:

  • Information and counseling of the patient and his or her family;

  • Enhancement of activities, exercise and sports therapy;

  • Psychosocial and psycho-educational interventions;

  • Pharmacological treatment.

Information and education should help patients understand CRF, as a result of cancer, and its treatment. This includes information on the multifactorial nature of CRF and the actual knowledge regarding its potential causes. Counseling should help CRF patients enhance general strategies to plan their activities and cope better with the restrictions due to CRF. Counseling also includes recommending patients to preserve energy, to prioritize and pace their activities or to delegate less important activities.[44,45] There is some evidence that such strategies can improve quality of life and reduce the subjective feeling of fatigue.[46] Information and counseling can be supported by brochures or interactive internet platforms, which are being provided in most countries by scientific cancer societies or pharmaceutical companies.

Interventions to promote (and reinforce) activity, exercise and physical training have proven to be effective strategies against fatigue and the continuing decrease of physical functional status.[47–49] Within the last decade many reviews and meta-analyses have demonstrated substantial evidence that moderate training, in combination with relaxation techniques, as well as body awareness help reduce subjective fatigue levels and improve patients' quality of life. A recently published Cochrane review shows moderate effects of physical training, especially for some subgroups of cancer patients and if applied early during ongoing adjuvant treatment.[50] Although various National Cancer Societies generally recommend physical activity to cancer patients, frequency, as well as intensity of exercise and training, should be carried out in an individualized fashion depending on patients' age, clinical status of cancer and subjective level of fitness.[101,51] Beyond these recommendations, there is only weak evidence for complementary medicine interventions such as acupuncture, massage or others.[52,53]

Recognizing that emotional distress is highly correlated with fatigue, psychoeducational interventions and counseling focus on coping strategies to optimize the patient's ability to deal with anxiety, depression and psychosocial distress. Some of these intervention programs include relaxation techniques[54] or meditation,[55] which may target underlying biologic mechanisms and reduce cancer-related distress by diminishing activation of the hypothalamic–pituitary–adrenal axis. The problem with these studies is that in most cases various outcome measures are addressed and fatigue has not been used as a primary outcome measure. Although there is some evidence that psychosocial interventions are able to decrease fatigue, a recently published Cochrane review shows moderate effects of psychosocial interventions in decreasing CRF.[56] Other reviews have pointed out that among psychosocial treatment approaches, cognitive behavioral interventions have been proven as being most effective against CRF.[57] In addition, it has been demonstrated that exercise training combined with psychoeducational interventions shows better effects than using only one type of intervention.[57] For the future, there is still a need for well-designed and adequately powered intervention studies to evaluate the direct effects of psychosocial interventions on decreasing CRF.

Among pharmacologic agents for the treatment of CRF, besides hematopoietics (only for anemia), corticosteroids and psychostimulants are discussed in particular. There are some randomized controlled trials showing effects of methylphenidate, especially for patients with severe levels of long-lasting fatigue and in progressive disease without psychiatric comorbidity.[58,59] Vertigo, increased blood pressure and dryness of the mouth have been described as possible side effects.[60] Although a recently published paper supports the effectiveness of methylphenidate, study results in general are still discussed controversially.[61] Effects seem to depend on the dosage used, the stage of cancer and treatment setting. In some European countries, methylphenidate is not approved for use in CRF. Against this background, methylphenidate may not be regarded as a standard medication for treating CRF.

Modafinil, which is approved only for the treatment of narcolepsy, has been shown effective for treating CRF in some studies, but a review of the literature analyzing studies up to 2008 concluded that modafinil cannot be recommended as a medication for CRF, owing to shortcomings in most of the studies.[62] A recent randomized study by Jean-Pierre et al. showed significant effects of modafinil for patients with severe fatigue at an early stage of treatment.[63] Against this background, modafinil cannot be regarded as a standard medication. Modafinil should not be used in patients with high arterial blood pressure, cardiac arrhythmia and psychiatric comorbidity.

Although there have been heterogenous results, National Comprehensive Cancer Network guidelines recommend psychostimulants for patients with moderate or high levels of fatigue during and after cancer treatment, when other causes of fatigue have been excluded.[101]

There are some other therapeutic agents that are less well studied for CRF. Those that are currently in the focus of clinical trials include L-carnitine, bupropion and selective serotonin reuptake inhibitors such as paroxetine.[64,65]

Overall, along with the conclusions of the two existing Cochrane reviews,[66,67] psychostimulants and CNS-stimulants are the most promising drugs, but placebo-controlled randomized trials are still lacking.


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