Key messages
We did not find any good-quality evidence about the benefits and risks of corticosteroids in treating adults with advanced cancer and cancer-related fatigue (CRF).
Future larger, well-designed studies are needed to determine if corticosteroids are of benefit or harmful in treating CRF.
Why is this review important?
Fatigue is a very common and troublesome symptom in people with advanced cancer, which greatly impacts their quality of life. Corticosteroid medicines are commonly used to treat CRF and other symptoms in people requiring palliative care. Corticosteroid medications can cause serious side effects, especially when used for a long period of time, so it is important to find out if they are effective at treating fatigue from cancer.
What did we want to find out?
We wanted to find out if corticosteroid medicines were better than inactive medicine (placebo), or other medicines to improve fatigue associated with cancer. We also wanted to find out if corticosteroids were associated with unwanted side effects when used for fatigue caused by advanced cancer.
What did we do?
We searched for studies that compared:
- corticosteroids with placebo; or
- corticosteroids with another active drug in adults with cancer.
We compared and summarised the results of the studies, and rated our confidence in the evidence, based on factors, such as study methods and sizes.
What did we find?
We found four studies that included 239 people requiring treatment for CRF. All studies lasted less than three weeks; the medicines were used for 14 days or less. Three studies compared corticosteroids with placebo, and one study compared corticosteroids with another active drug (modafinil). The corticosteroid medicines used were methylprednisolone and dexamethasone, in a comparable low dose. All studies were small, with fewer than 100 people included.
It is currently uncertain whether corticosteroids reduce CRF. It is unclear if there are more side effects in people using short-term corticosteroids for CRF. We do not know if there is an improvement in quality of life for people taking corticosteroids for CRF.
If people use corticosteroids to manage their CRF, they should discuss possible side effects, and how long they will use them, with their doctor. Other studies have found that long-term use can be associated with harmful side effects.
What are the limitations of the evidence?
We are not confident in the evidence because there were only four small studies that looked at the effect of corticosteroids in cancer-related fatigue. All studies included in this review were likely to introduce errors.
How up to date is this evidence?
This evidence is up to date to 18 July 2022.
There is insufficient evidence to support or refute the use of systemic corticosteroids in adults with cancer and CRF.
We included four small studies that provided very low-certainty of evidence for the efficacy of corticosteroids in the management of CRF.
Further high-quality randomised controlled trials with larger sample sizes are required to determine the effectiveness of corticosteroids in this setting.
Fatigue is the most commonly reported symptom in people with advanced cancer. Cancer-related fatigue (CRF) is pervasive and debilitating, and can greatly impact quality of life (QoL). CRF has a highly variable clinical presentation, likely due to a complex interaction of multiple factors. Corticosteroids are commonly used to improve CRF, but the benefits are unclear and there are significant adverse effects associated with long-term use. With the increasing survival of people with metastatic cancer, the long-term effects of medications are becoming increasingly relevant. Since the impact of CRF can be immensely debilitating and can negatively affect QoL, its treatment warrants further review.
To determine the benefits and harms of corticosteroids compared with placebo or an active comparator in adults with advanced cancer and CRF.
We searched CENTRAL, MEDLINE, Embase, CINAHL, Science Citation Index (ISI Web of Science), LILACS, and two clinical trial registries from inception to 18 July 2022.
We included randomised controlled trials in adults aged ≥18 years. We included participants with advanced cancer who were suffering from CRF. We included trials that randomised participants to corticosteroids at any dose, by any route, administered for the relief of CRF; compared to placebo or an active comparator, including supportive care or non-pharmacological treatments.
Three review authors independently assessed titles identified by the search strategy; two review authors assessed risk of bias; and two extracted data. We extracted the primary outcome of participant-reported fatigue relief using validated scales and secondary outcomes of adverse events, serious adverse events and QoL. We calculated the risk ratio with 95% confidence intervals (CIs) between groups for dichotomous outcomes. We measured arithmetic mean and standard deviation, and reported the mean difference (MD) with 95% CI between groups for continuous outcomes. We used standardised mean difference (SMD) with 95% CIs when an outcome was measured with different instruments measuring the same construct. We used a random-effects model to meta-analyse the outcome data. We rated the certainty of the evidence using GRADE and created two summary of findings tables.
We included four studies with 297 enroled participants; data were available for only 239 participants. Three studies compared corticosteroid (equivalent ≤ 8 mg dexamethasone) to placebo. One study compared corticosteroid (dexamethasone 4 mg) to an active comparator (modafinil 100 mg). There were insufficient data to evaluate subgroups, such as dose and duration of treatment. One study had a high risk of performance and detection bias due to lack of blinding, and one study had a high risk of attrition bias. Otherwise, we assessed risks of bias as low or unclear.
Comparison 1: corticosteroids compared with placebo
Participant-reported fatigue relief
The was no clear difference between corticosteroids and placebo (SMD -0.46, 95% CI -1.07 to 0.14; 3 RCTs, 165 participants, very low-certainty evidence) for relief of fatigue at one week of the intervention. We downgraded the certainty of the evidence three times for study limitations due to unclear risk of bias, imprecision, and inconsistency.
Adverse events
There was no clear difference in the occurrence of adverse events between groups, but the evidence is very uncertain (3 RCTs, 165 participants; very low-certainty evidence).
Serious adverse events
There was no clear difference in the occurrence of serious adverse events between groups, but the evidence is very uncertain (2 RCTs, 118 participants; very low-certainty evidence).
Quality of lIfe
One study reported QoL at one week using the Edmonton Symptom Assessment System (ESAS) well-being, and found no clear difference in QoL between groups (MD -0.58, 95% CI -1.93 to 0.77). Another study measured QoL using the Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs (QoL-ACD), and found no clear difference between groups. There was no clear difference between groups for either study, but the evidence is very uncertain (2 RCTs, 118 participants; very low-certainty evidence).
Comparison 2: corticosteroids compared with active comparator (modafinil)
Participant-reported fatigue relief
There was improvement in fatigue from baseline to two weeks in both groups (modafinil MD 10.15, 95% CI 7.43 to 12.87; dexamethasone MD 9.21, 95% CI 6.73 to 11.69), however no clear difference between the two groups (MD -0.94, 95% CI -4.49 to 2.61; 1 RCT, 73 participants, very low-certainty evidence). We downgraded the certainty of the evidence three times for very serious study limitations and imprecision.
Adverse events
There was no clear difference in the occurrence of adverse events between groups, but the evidence is very uncertain (1 RCT, 73 participants; very low-certainty evidence).
Serious adverse events
There were no serious adverse events reported in either group (1 RCT, 73 participants; very low-certainty evidence).
Quality of lIfe
One study measured QoL at two weeks, using the ESAS-well-being. There was marked improvement in QoL from baseline in both groups (modafinil MD -2.43, 95% CI -2.88 to -1.98; dexamethasone MD -2.16, 95% CI -2.68 to -1.64), however no clear difference between the two groups (MD 0.27, 95% CI -0.39 to 0.93; 1 RCT, 73 participants, very low-certainty evidence).