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Meta-Analysis
. 2010 Jul 7;2010(7):CD006704.
doi: 10.1002/14651858.CD006704.pub3.

Drug therapy for the management of cancer-related fatigue

Ollie Minton  1 , Alison Richardson, Michael Sharpe, Matthew Hotopf, Patrick Stone
Affiliations
Meta-Analysis

Drug therapy for the management of cancer-related fatigue

Ollie Minton et al. Cochrane Database Syst Rev. .

Abstract

Background: This is an updated version of the original Cochrane review published in issue 1 2008 (Minton 2008). Cancer-related fatigue (CRF) is common, under-recognised and difficult to treat. There have been studies 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.

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

Search strategy: We searched the Cochrane Central Register of Controlled Trials (from Issue 2 2007) MEDLINE and EMBASE from January 2007 to October 2009 and a selection of cancer journals. We searched references of identified articles and contacted authors to obtain unreported data.

Selection criteria: Studies 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: Fifty studies met the inclusion criteria. Six additional studies were identified since the original review. Only 31 of these studies involving 7104 participants were judged to have used a sufficiently robust measure of fatigue and thus were deemed suitable for detailed analysis. The drugs were still analysed by class (psychostimulants; haemopoietic growth factors; antidepressants and progestational steroids). Methylphenidate showed a small but significant improvement in fatigue over placebo (Z = 2.83; P = 0.005). Since the publication of the original review increased safety concerns have been raised regarding erythropoietin and this cannot now be recommended in practice.There was a very high degree of statistical and clinical heterogeneity in the trials and the reasons for this are discussed.

Authors' conclusions: There is increasing evidence that psychostimulant trials provide evidence for improvement in CRF at a clinically meaningful level. There is still a requirement for a large scale RCT of methylphenidate to confirm the preliminary results from this review. There is new safety data which indicates that the haemopoietic growth factors are associated with increased adverse outcomes. These drugs can no longer be recommended in the treatment of CRF. Readers of the first review should re-read the document in full.

PubMed Disclaimer

Conflict of interest statement

Dr Stone previously received an unrestricted (£15k) educational grant from Orthobiotech (UK) in 2001 to undertake a small research project on erythrocyte function in patients with cancer.

Figures

1
1
Forest plot of comparison: 5 Psychostimulants versus placebo, outcome: 5.1 Fatigue score change.
2
2
Forest plot of comparison: 1 Erythropoetin versus no intervention (sub analysis versus placebo), outcome: 1.1 Difference in fatigue score.
3
3
Forest plot of comparison: 2 Darbopoetin versus placebo, outcome: 2.1 Fatigue score change.
4
4
Forest plot of comparison: 4 Antidepressants versus placebo, outcome: 4.1 Fatigue score change.
5
5
Forest plot of comparison: 3 Progestational steroids versus placebo, outcome: 3.1 Fatigue score change.
6
6
Forest plot of comparison: 7 Adverse events, outcome: 7.1 Adverse events (grouped).
7
7
Forest plot of comparison: 8 Withdrawals, outcome: 8.1 Withdrawals.
1.1
1.1. Analysis
Comparison 1 Erythropoetin versus no intervention (subanalysis versus placebo), Outcome 1 Difference in fatigue score.
2.1
2.1. Analysis
Comparison 2 Darbopoetin versus placebo, Outcome 1 Fatigue score change.
3.1
3.1. Analysis
Comparison 3 Progestational steroids versus placebo, Outcome 1 Fatigue score change.
4.1
4.1. Analysis
Comparison 4 Antidepressants versus placebo, Outcome 1 Fatigue score change.
5.1
5.1. Analysis
Comparison 5 Psychostimulants versus placebo, Outcome 1 Fatigue score change.
6.1
6.1. Analysis
Comparison 6 Haemopoetic growth factors versus no intervention, Outcome 1 Erythropoetin or darbopoetin versus no treatment.
6.2
6.2. Analysis
Comparison 6 Haemopoetic growth factors versus no intervention, Outcome 2 Studies with FACT F.
7.1
7.1. Analysis
Comparison 7 Adverse events, Outcome 1 Adverse events (grouped).
8.1
8.1. Analysis
Comparison 8 Withdrawals, Outcome 1 Withdrawals.
See this image and copyright information in PMC

Update of

References

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References to studies excluded from this review

Barton 2009 {published data only}
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Heras 2009 {published data only}
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References to ongoing studies

Bauer 2007 {unpublished data only}
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Cruciani 2007 {unpublished data only}
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Dagnelie 2007 {unpublished data only}
    1. Dagnelie P. Application of adenosine‐5‐triphosphate infusions in palliative home care. www.clinicaltrials.gov Accessed 1 August 2007. [CTN97280223]
Drappatz 2009 {unpublished data only}
    1. Drappatz J. A Randomized Placebo‐Controlled Trial of Armodafinil (Nuvigil) for Fatigue in Patients With Malignant Gliomas. www.clinicaltrials.gov accessed 1.10.09. [NCT 00766467]
Duffy 2009 {unpublished data only}
    1. Duffy P. Study With Modafinil in Patients Treated With Docetaxel‐Based Chemotherapy for Metastatic Breast or Prostate Cancer (MOTIF. www.clinicaltrials.gov clinicaltrials.gov.
Frizell 2007 {unpublished data only}
    1. Frizell B. Co‐enzyme Q10 in relieving treatment related fatigue in women with breast cancer. www.clincialtrials.gov Accessed 1 August 2007. [NCT00096356]
Hutson 2007 {unpublished data only}
    1. Hutson P. Methylphenidate in treating patients with melanoma. www.clinicaltrials.gov Accessed 1 August 2007. [NCT00003266]
Morrow 2007 {published data only}
    1. Morrow G. modafinil for treating fatigue in patients receiving chemotherapy for cancer. www.clinicaltrials.gov Accessed 1 August 2007. [NCT00042848]
Roth 2007 {published data only}
    1. Roth A. Psychostimulants for fatigue in prostate cancer. www.clinicaltrials.gov Accessed 1 August 2007. [NCT00138138]
Sood 2006 {published data only}
    1. Sood A, Dakhill S. Methylphenidate in treating fatigue caused by cancer. www.clinicaltrials.gov Accessed 1 August 2007. [NCT00376675]
Thomas 2007 {unpublished data only}
    1. Thomas CR. Etanercept versus placebo with radiation therapy to combat fatigue and anorexia. www.clinicaltrials.gov Accessed 1 August 2007. [NCT00127387]
Wee 2009 {unpublished data only}
    1. Wee B. modafinil for the treatment of fatigue in advanced lung cancer. www.clinicaltrials.gov. [NCT 008829322]

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