Journal of the National Cancer Institute Advance Access originally published online on August 11, 2008
JNCI Journal of the National Cancer Institute 2008 100(16):1155-1166; doi:10.1093/jnci/djn250
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Published by Oxford University Press 2008.
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A Systematic Review and Meta-Analysis of the Pharmacological Treatment of Cancer-Related Fatigue
Affiliations of authors: St George's University of London, London, UK (OM, PS); Kings College London, London, UK (AR); University of Edinburgh, Edinburgh, UK (MS); Institute of Psychiatry Kings College London, London, UK (MH)
Correspondence to: Ollie Minton, Clinical Research Fellow, Division of Mental Health, St George's University of London, Cranmer Terrace, London SW17 ORE (e-mail: ominton{at}sgul.ac.uk).
Background: Cancer-related fatigue is an important clinical problem. It is common, distressing, and often difficult to treat. There is a role for drug treatment of cancer-related fatigue, but no consensus has been reached on which drugs are useful. This systematic review and meta-analysis aims to review the available evidence and make recommendations for practice and research.
Methods: We searched the Cochrane register of controlled trials (through the second quarter 2007), Medline (January 1, 1966, through August 1, 2007), and EMBASE (January 1, 1980, through August 1, 2007) by use of a predetermined list of search terms. Cochrane Collaboration meta-analysis review methodology was used for this study. The change in fatigue score on the instrument used in each study and other outcomes of interest (adverse events and withdrawal rates) were compared between treatment and control arms by use of the standardized mean difference (SMD) with 95% confidence intervals (CIs). All statistical tests were two-sided.
Results: We identified 27 eligible trials of drug treatments for cancer-related fatigue (with a total of 6746 participants). The overall effect size for all drug classes was small. A meta-analysis of two studies (n = 264 patients) indicated that methylphenidate (a psychostimulant) was superior to placebo (standardized mean difference [SMD] in change in fatigue score = –0.30, 95% confidence interval [CI] = –0.54 to –0.05; P = .02) for treating cancer-related fatigue. A meta-analysis of 10 studies (n = 2226 patients) evaluating erythropoietin in anemic cancer patients who were undergoing chemotherapy indicated that erythropoietin was superior to placebo (SMD = –0.30, 95% CI = –0.46 to –0.29; P = .008). Among anemic patients (four studies with n = 964 patients), improvement in fatigue was associated with darbepoetin treatment compared with placebo treatment (SMD = –0.13, 95% CI = –0.27 to 0.00; P = .05). Progestational steroids and paroxetine were no better than placebo in the treatment of cancer-related fatigue.
Conclusions: There is some evidence that treatment of cancer-related fatigue with methylphenidate appears to be effective. More robust evidence indicates that treatment with hematopoietic agents appears to relieve cancer-related fatigue caused by chemotherapy-induced anemia. Further confirmatory trials are required for both observations.
| CONTEXT AND CAVEATS Prior knowledge Cancer-related fatigue is an important clinical problem, but which drugs are useful for treatment remains unclear. Study design Systematic review and meta-analysis of 27 randomized trials of drug treatments for cancer-related fatigue that met prospective criteria for review (n = 6746 participants). Contribution Limited evidence was found that treatment of cancer-related fatigue with methylphenidate appears to be effective. Somewhat more robust evidence was found that treatment with hematopoietic agents appears to relieve cancer-related fatigue caused by chemotherapy-induced anemia. Overall effects of the treatments on fatigue were small, however. Implications Because overall effect sizes are small, potential implications for treatment should be tempered. Further confirmatory trials are required for both observations. Limitations Some reporting bias may exist. The review did not include nondrug interactions. From the Editors
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Manuscript received October 29, 2007; revised May 16, 2008; accepted June 18, 2008.
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J Natl Cancer Inst 2008 100: 1119.
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