Cancer patients often experience fatigue, a pervasive and persistent sense of tiredness that is not alleviated by rest or sleep. The causes of cancer-related fatigue are multi-factorial, which makes identification of underlying mechanisms difficult. Thus, there is a lack of targeted treatments for cancer-related fatigue, and managing this symptom remains largely empirical. To gain better understanding of the most promising treatments for cancer-related fatigue, a recent study reviewed randomized trials in the Cochrane register of control trials, Medline, and EMBASE to assess the efficacy of various drug treatments for this symptom.

The review utilized the following inclusion criteria for studies and trials: 1) randomized controlled trials designed to test a drug versus placebo and 2) trials using a robust measure of fatigue as an outcome. Of the 5,841 titles and abstracts screened, 27 met the inclusion criteria and were subsequently divided by drug type for ease of analysis.

Two types of studies that showed favorable outcomes in the treatment of cancer-related fatigue focused on methylphenidate and hematopoietic growth factors. Two methylphenidate studies showed significant reduction in fatigue when compared to placebo treatment. In terms of hematopoietic treatments, erythropoietin and darbepoetin treatment also showed significant improvements in fatigue over placebo treatments. Studies of antidepressants and progestational steroids were also reviewed, but no significant treatment benefits were found. Finally, a high rate of adverse events was found in all of the studies that were reviewed, but these events were not related to medication type.

This review of literature is the first to assess the effects of common pharmacological treatments on cancer-related fatigue. Although methylphenidate and hematopoietic treatments seem to be beneficial, several limitations must be taken into account. For example, due to a lack of complete availability for data from certain trials, reporting bias may exist. Also, the overall size of the reviewed trials is small, and therefore, implications for further research should be tempered until more comprehensive reviews are done. However, the evidence thus far points the way to studies that examine the optimization of methylphenidate and hematopoietic treatments, as well as to research in the basic science of fatigue itself. Eventually, these types of studies could be combined with tailored exercise programs and cognitive behavioral therapy to provide the best possible treatment for cancer-related fatigue.

Minton O, Richardson A, Sharpe M, Hotopf M, Stone P. A systematic review and meta-analysis of the pharmacological treatment of cancer-related fatigue. J Natl Cancer Inst. 2008 Aug 20;100(16):1155-66.

NAAC Expert Commentary:
Fatigue is a distressing symptom of many diseases, and is very prevalent among cancer patients. In addition to compromising one’s quality of life, fatigue interferes with the patient’s social activities and personal relationships, and can negatively effect the patient’s caregivers as well. The mechanism of fatigue is still elusive and the treatment unsatisfactory. This well documented meta-analysis demonstrates that two forms of treatment have proven effective in cancer patients: metilphenidate (Provigil), and ESAs, that is epoetin α and darbepoetin α. The latter were effective mainly in patients with Hb levels lower than 12 g/dL.

This meta-analysis provides solid evidence to support the current practices for managing cancer-related fatigue. Unfortunately, the study leaves a number of questions unresolved. The first and most important is whether the management of fatigue improves the patient and his/her caregiver’s social activity and personal relationships. If it does not, one may question the benefit of these expensive forms of treatment promoted.

The second question concerns the safety of the ESAs, which has been debated in recent studies. The increased incidence of deep vein thrombosis and the potential risk of stimulating cancer growth may be too high a price to pay if the benefit of treatment is limited to the relief of a symptom.

Another conclusion of the meta-analysis which deserves commenting was the fact that the treatment with paroxetine was ineffective in a randomized controlled study does not mean that antidepressants should not play an important role in the management of fatigue. It may simply mean that the studies did not have adequate power, or the patients were inadequately screened for depression.

In conclusion, it is encouraging to know that the correction of anemia and the use of psychostimulants may improve fatigue. However, studies are still needed to determine the mechanism of fatigue and the benefits of treating this symptom.

Last Updated: February 4, 2009