In a study (ABCD; Alleviating Breathlessness in Cancer Patients with Dexamethasone) reported in The Lancet Oncology, David Hui, MD, MS, MSc, and colleagues found that high-dose dexamethasone did not improve dyspnea compared with placebo in patients with cancer and was associated with greater frequency of adverse events.
As stated by the investigators, “Systemic corticosteroids are commonly prescribed for palliation of dyspnea in patients with cancer, despite scarce evidence to support their use. We aimed to assess the effect of high-dose dexamethasone vs placebo on cancer-related dyspnoea.”
Study Details
In the double-blind trial, ambulatory patients from The University of Texas MD Anderson Cancer Center and Lyndon B. Johnson General Hospital (both in Houston) were screened between January 2018 and April 2021, with 128 randomly assigned 2:1 to receive dexamethasone (n = 85) or placebo (n = 43). Patients had to have an average dyspnea intensity score during the week prior to enrollment of ≥ 4 on a numerical rating scale (NRS) of 0 (none) to 10 (worst). Treatment consisted of 8 mg of oral dexamethasone every 12 hours for 7 days followed by 4 mg every 12 hours for 7 days or matching placebo for 14 days. The primary outcome measure was change in dyspnea NRS intensity over the past 24 hours from baseline to day 7 (±2 days).
Effect on Dyspnea
Enrollment was stopped after the second preplanned interim analysis due to meeting of the futility criterion.
The mean change in dyspnea NRS intensity from baseline to day 7 (±2 days) was –1.6 (95% confidence interval [CI] = –2.0 to –1.2) in the dexamethasone group vs –1.6 (95% CI = –2.3 to –0.9) in the placebo group, with no significant between-group difference observed (mean difference = 0.0, 95% CI = –0.8 to 0.7, P = .48).
High-dose dexamethasone did not improve dyspnea in patients with cancer more effectively than placebo and was associated with a higher frequency of adverse events. These data suggest that dexamethasone should not be routinely given to unselected patients with cancer for palliation of dyspnea.— David Hui, MD, MS, MSc, and colleagues
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No significant differences between the dexamethasone vs placebo groups were observed in mean change in NRS score for dyspnea from day 0 to day 14 (mean difference = 0.2, P > .99), activity-adjusted dyspnea from day 0 to day 7 (mean difference = –0.45, P = .21) or to day 14 (mean difference = –0.44, P = .31), or dyspnea unpleasantness from day 0 to day 7 (mean difference = 0.4, P = .97) or to day 14 (mean difference = 0.6, P = .93).
Adverse Events
A total of 45 grade ≥ 3 adverse events occurred in patients in the dexamethasone group vs 7 in the placebo group; the most common were infections (11% vs 7%), insomnia (8% vs 2%), and neuropsychiatric symptoms (4% vs 0%). Adverse events of any grade that were more common in the dexamethasone group were insomnia, neuropsychiatric symptoms, infections, dyspepsia, edema, hiccups, flushing, and respiratory distress. Serious adverse events, all resulting in hospital admissions, occurred in 24 patients (28%) in the dexamethasone group and 3 patients (7%) in the placebo group. No treatment-related deaths were reported.
The investigators concluded, “High-dose dexamethasone did not improve dyspnea in patients with cancer more effectively than placebo and was associated with a higher frequency of adverse events. These data suggest that dexamethasone should not be routinely given to unselected patients with cancer for palliation of dyspnea.”
Dr. Hui, of the Department of Palliative, Rehabilitation & Integrative Medicine, MD Anderson Cancer Center, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the National Cancer Institute. For full disclosures of the study authors, visit thelancet.com.
