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Drug therapy for the management of cancer related fatigue

  • Review
  • Intervention




Cancer related fatigue (CRF) is common, under-recognised and difficult to treat. There have been trials looking at drug interventions to improve CRF but results have been conflicting depending on the population studied and outcome measures used. No previous reviews of this topic have been exhaustive or have synthesised all available data.


To assess the efficacy of drugs for the management of CRF.

Search strategy

We searched the Cochrane Central Register of Controlled Trials (Issue 1, 2007), MEDLINE (1966 to March 2007) and a selection of cancer journals. We searched references of identified articles and contacted authors to obtain unreported data.

Selection criteria

Trials were included in the review if they 1) assessed drug therapy for the management of CRF compared to placebo, usual care or a non-pharmacological intervention in 2) randomised controlled trials (RCT) of 3) adult patients with a clinical diagnosis of cancer.

Data collection and analysis

Two review authors independently assessed trial quality and extracted data. Meta-analyses were performed on different drug classes using continuous variable data.

Main results

Forty-five trials met the inclusion criteria. Only 27 of these trials involving 6746 participants were judged to have used a sufficiently robust measure of fatigue and thus were deemed suitable for detailed analysis. The drugs were analysed by class (psychostimulants; haemopoetic growth factors; antidepressants and progestational steroids). Methylphenidate showed a small but significant improvement in fatigue over placebo (Z = 2.40; P = 0.02). Erythropoietin showed a small but significant improvement in fatigue (for anaemic patients receiving chemotherapy) compared to placebo (Z = 2.67; P = 0.008). Darbopoietin also demonstrated a smaller but significant improvement in fatigue over placebo (Z = 1.96; P = 0.05). Paroxetine and progestational steroids demonstrated no superiority over placebo in treating CRF. There was a very high degree of statistical and clinical heterogeneity in the trials and the reasons for this are discussed. It was not possible to determine optimum doses as a result of this review.

Authors' conclusions

Erythropoietin and darbopoetin (for anaemic patients on chemotherapy) and psychostimulant trials provide evidence for improvement in CRF at a clinically meaningful level. There are no data to support the use of paroxetine or progestational steroids for the treatment of CRF. The obvious candidate drug for use in a large scale RCT is methylphenidate to confirm the preliminary results from this review.

Plain language summary

Drug therapy for the management of cancer related fatigue

Fatigue associated with cancer is a significant problem. It can occur because of side effects of treatment or because of the disease itself. It can have a significant impact on a person's ability to function. The causes of fatigue are not fully understood and so it is very difficult to treat appropriately. This review has examined drug treatment for fatigue as it represents one of the ways this problem can be tackled. The review authors looked at trials in all types of cancer and at all stages of treatment. Forty five trials met the inclusion criteria but only 27 (6746 participants) were deemed suitable for detailed analysis as they explored fatigue in sufficent detail. They found mixed results with some drugs showing an effect on fatigue - most notably drugs that stimulate red blood cell production and also drugs that improve levels of concentration. Methylphenidate, a stimulant drug that improves concentration, is effective for the management of cancer related fatigue but the small samples used in the available studies mean more research is needed to confirm its role. Erythropoietin and darbopoetin, drugs that improve anaemia, are effective in the management of cancer related fatigue in patients who are anaemic as a result of chemotherapy. These drugs are not without side effects and they should be used under expert supervision and their effect closely monitored.