Pharmacological Interventions for the Management of Cancer-Related Fatigue Among Cancer Survivors: Systematic Review and Meta-Analysis

Abstract

Objective: Current guidelines have different recommendations on applying pharmacological interventions for managing cancer-related fatigue (CRF) among cancer survivors. This systematic review aims to synthesize clinical evidence on pharmacological interventions for managing CRF.

Methods: Five databases were searched for potential randomized controlled trials (RCTs) from their inception until October 2020. RCTs assessing the effect of pharmacological treatments for CRF among cancer survivors were considered eligible. Clinical significance was determined by comparing the estimated effect with that of minimal important difference (MID). The risk of bias of each included RCT was appraised using the Cochrane risk of bias tool for randomized trials 2. Data were synthesized using random-effect pairwise meta-analyses.

Results: A total of 15 RCTs (1238 participants) were included. The majority presented some concerns of bias arising from the randomization process and selection of the reported results. Meta-analysis showed that psychostimulant and wakefulness agents had statistically significant while clinically insignificant effects on the treatment of CRF (pooled weighted mean difference [WMD]: 2.8, 95% confidence interval [CI]: 0.2-5.4, I²: 0%, 3 RCTs, MID: 3.0-6.0). Three natural products, including Renshen Yangrong Tang (mean difference [MD]: -16.1, 95% CI: -8.9 to -23.3, MID: -17.3 to -11.4), Tualang honey (MD: 11.2, 95% CI: 7.1-15.3, MID: 3.0-6.0), and Shenmai injection plus Peptisorb (MD: -1.6, 95% CI: -2.1 to -1.1, MID: -1.1 to -0.8) demonstrated statistically and clinically significant effect in reducing CRF.

Conclusions: Existing evidence showed promising effects of 3 natural products in reducing CRF among cancer survivors. The results from this study need to be further confirmed with well-designed and adequately powered RCTs that use validated instruments for the measurement of CRF.

Keywords: cancer survivors; drug therapy; fatigue; meta-analysis; systematic review.

Figure 1.

PRISMA flow diagram for literature search and selection.

Figure 2.

Risk of bias among included randomized controlled trials. I, bias arising from the randomization process; II, bias due to deviations from intended interventions; III, bias due to missing outcome data; IV, bias in the measurement of the outcome; V, bias in the selection of the reported result.

Figure 3.

Psychostimulants and wakefulness agents versus placebo in reducing fatigue among cancer survivors: meta-analysis. Follow-up duration: trials used FACIT-F: 4 to 8 weeks; trial used MFI-20: 13 weeks; trial used CIS: 6 weeks. Abbreviations: FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue Scale; MD, mean difference; MFI-20, Multidimensional Fatigue Inventory; CIS, checklist individual strength.