The efficacy of placebo for the treatment of cancer-related fatigue: a systematic review and meta-analysis

  • Pedro Nazareth Aguiar JuniorEmail author
  • Carmelia Maria Noia Barreto
  • Daniel de Iracema Gomes Cubero
  • Auro del Giglio
Original Article



Cancer-related fatigue (CRF) is a common symptom among patients with cancer. The efficacy of placebo, however, was never the main objective of any meta-analysis. Predicting the efficacy of placebo may facilitate researchers in designing future clinical trials for the treatment of CRF.


We performed a systematic review searching for prospective clinical trials comparing any treatment versus placebo for the treatment of CRF. We included studies that enrolled patients with any primary site of neoplasia and any stage of cancer. We excluded all studies that assessed fatigue related to any treatment. The primary endpoint of this study is the mean effect of placebo on fatigue according to the Functional Assessment of Chronic Illness (FACIT-F) and Brief Fatigue Inventory (BFI) scales. The secondary endpoint was the proportion of patients who reported improvement in fatigue (response rate).


We found 520 studies, and 29 studies with 3758 participants were included in the meta-analysis. Placebo had a mean effect of + 4.88 (95%CI + 2.45 to + 7.29) using the FACIT-F scale, although it was statistically worse than the interventions studied (p = 0.005). Using the BFI scale, placebo had an average effect of + 0.64 (95%CI + 0.02 to + 1.30), although it was also worse than the other interventions studied (p = 0.002). In terms of the response rate, 29% (95%CI 25–32%) of patients taking a placebo reported a significant improvement in CRF compared with 36% of patients treated with other interventions (p = 0.030).


Placebo treatments had a significant effect on CRF, and predicting these effects may help design future studies for CRF.


Fatigue Cancer Placebo effect Palliative care 



The authors thank Dr. Ana Luiza Cabrera for her kind advice in developing the search strategy.


This study was funded by Centro de Estudos e Pesquisa de Hematologia e Oncologia. Faculdade de Medicina do ABC, Santo André, Brazil.

Compliance with ethical standards

Conflict of interest

PNAJ has received speaker’s honoraria from Merck Co. All other authors have no conflicts to disclose.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Pedro Nazareth Aguiar Junior
    • 1
    • 2
    Email author
  • Carmelia Maria Noia Barreto
    • 3
  • Daniel de Iracema Gomes Cubero
    • 1
  • Auro del Giglio
    • 1
  1. 1.Centro de Estudos e Pesquisa de Hematologia e OncologiaFaculdade de Medicina do ABCSanto AndréBrazil
  2. 2.Américas Centro de Oncologia IntegradoSão PauloBrazil
  3. 3.MD Anderson Cancer CenterHoustonUSA

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