Incidence of fatigue and low-dose corticosteroid use in prostate cancer patients receiving systemic treatment: a meta-analysis of randomized controlled trials
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Cancer-related fatigue (CRF) is a complex condition that is reported in > 50% of cancer patients. In men with castration-resistant prostate cancer (CRPC), CRF was reported in 12–21% of patients. Approved systemic therapy against CRPC is commonly administered in combination with androgen-deprivation treatment (ADT) and, in some cases, with daily, low-dose corticosteroids. Importantly, the use of low-dose corticosteroids is associated with multiple negative effects, including reduced muscle mass. On these grounds, we hypothesized that the chronic use of corticosteroids may increase the incidence of fatigue in patients with prostate cancer.
We reviewed all randomized trials published during the last 15 years conducted in patients with prostate cancer receiving systemic treatment and we performed a sub-group analysis to gather insights regarding the potential differences in the incidence of fatigue in patients receiving vs. not receiving daily corticosteroids as part of their systemic anti-neoplastic regimen.
Overall, 22,734 men enrolled in prospective randomized phase II and III trials were evaluable for fatigue. Estimated pooled incidence of grade 1–2 fatigue was 30.89% (95% CI = 25.34–36.74), while estimated pooled incidence of grade 3–4 fatigue was reported in 3.90% (95% CI = 2.91–5.02). Sub-group analysis showed that grade 3–4 fatigue was approximately double in patients who received daily corticosteroids as part of their anti-neoplastic treatment (5.58; 95% CI = 4.33–6.98) vs. those who did not (2.67%; 95% CI = 1.53–4.11).
Our findings highlight the need for ad hoc-designed prospective clinical trials to investigate whether the benefits associated with low-dose, daily corticosteroids outweigh the risks associated with corticosteroid-related adverse events such as fatigue.
KeywordsProstate cancer Meta-analysis Fatigue Corticosteroids
Ferro: Project development; Manuscript editing. Di Lorenzo: Project development; Manuscript editing. de Cobelli: Project development; Manuscript editing. Bruzzese: Data analysis. Pignataro: Data collection. Borghesi: Project development. Musi: Project development. Vartolomei: Project development. Cosimato: Data collection. Serino: Data collection. Ieluzzi: Data collection. Terracciano Project development. Damiano Project development; Manuscript editing. Cantiello Project development; Manuscript editing. Mistretta Project development; Manuscript editing. Muto Project development; Manuscript editing. Lucarelli Project development; Manuscript editing. De Placido Project development; Manuscript editing. Buonerba Project development; Data management; Manuscript writing.
Compliance with ethical standards
Conflict of interest
No relevant conflicts by any of the authors are to be disclosed.
The authors have no potential conflicts of interest to disclose relevant to this work. This work is a systematic review of published data, so it does not directly involve human participants and/or animals, not did it require any informed consent or ethics committee approval.
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