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.

Management of Fatigue in Patients with Advanced Cancer

“…A variety of other agents have been investigated for their role in reducing CRF including paroxetine, bupropion, donepezil, thyrotropin-releasing hormone, melatonin, testosterone and ATP. None of these can be recommended due to a lack of good quality evidence of benefit ( 6 , 8 , 50 , 73 , 74 ).…”

Astragalus membranaceus (Huang Qi) for cancer-related fatigue

“…The incidence of CRF varies with tumors, treatments, and evaluation methods, but it is higher than 80% in most reports. [2][3][4] The burden of CRF grows as the incidence of cancer increases year by year. CRF exists in cancer treatment and may last for months or even years.…”

“…It is one of the most common complications of cancer. The incidence of CRF varies with tumors, treatments, and evaluation methods, but it is higher than 80% in most reports [2–4] . The burden of CRF grows as the incidence of cancer increases year by year.…”

“…Its management is also an essential part of cancer treatment. Current intervention methods include exercise, psychology, and mood, anemia, and nutrition treatments [4,6,7] . There is still a lack of effective treatment drugs.…”

Meta-Analysis of Pharmacological, Nutraceutical and Phytopharmaceutical Interventions for the Treatment of Cancer Related Fatigue

“…The most investigated medications among them include psychostimulants, ginseng, corticosteroids, megestrol, mistletoe, guarana, antidepressants specifically selective serotonin receptor reuptake inhibitors (SSRI's). Other agents investigated include Hemopoietin agents [13], Donepezil [14], Testosterone [15,16], Omega 3 polyunsaturated fatty acids [17][18][19], L-carnitine [20][21][22], Astragalus membranaceus [23], Ashwagandha [24], Thyrotropin releasing hormone [25], Microbiome [26], Coenzyme Q10 [27], Micro and macronutrients supplementation such as protein rich diet, vitamin or mineral supplementation [28], and others [29][30][31][32].…”