TY - JOUR
T1 - Effect of dexamethasone on dyspnoea in patients with cancer (ABCD)
T2 - a parallel-group, double-blind, randomised, controlled trial
AU - Hui, David
AU - Puac, Veronica
AU - Shelal, Zeena
AU - Dev, Rony
AU - Hanneman, Sandra K.
AU - Jennings, Kristofer
AU - Ma, Hilary
AU - Urbauer, Diana L.
AU - Shete, Sanjay
AU - Fossella, Frank
AU - Liao, Zhongxing
AU - Blumenschein, George
AU - Chang, Joe Y.
AU - O'Reilly, Michael
AU - Gandhi, Saumil J.
AU - Tsao, Anne
AU - Mahler, Donald A.
AU - Bruera, Eduardo
N1 - Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/10
Y1 - 2022/10
N2 - Background: Systemic corticosteroids are commonly prescribed for palliation of dyspnoea in patients with cancer, despite scarce evidence to support their use. We aimed to assess the effect of high-dose dexamethasone versus placebo on cancer-related dyspnoea. Methods: The parallel-group, double-blind, randomised, controlled ABCD (Alleviating Breathlessness in Cancer Patients with Dexamethasone) trial was done at the at the University of Texas MD Anderson Cancer Center and the general oncology clinic at Lyndon B Johnson General Hospital (both in Houston, TX, USA). Ambulatory patients with cancer, aged 18 years or older, and with an average dyspnoea intensity score on an 11-point numerical rating scale (NRS; 0=none, 10=worst) over the past week of 4 or higher were randomly assigned (2:1) to receive dexamethasone 8 mg orally every 12 h for 7 days followed by 4 mg orally every 12 h for 7 days, or matching placebo capsules for 14 days. Pharmacists did permuted block randomisation with a block size of six, and patients were stratified by baseline dyspnoea score (4–6 vs 7–10) and study site. Patients, research staff, and clinicians were masked to group assignment. The primary outcome was change in dyspnoea NRS intensity over the past 24 h from baseline to day 7 (±2 days). Analyses were done by modified intention-to-treat (ie, including all patients who were randomly assigned and started the study treatment, regardless of whether they completed the study). Enrolment was stopped after the second preplanned interim analysis, when the futility criterion was met. This study is registered with ClinicalTrials.gov (NCT03367156) and is now completed. Findings: Between Jan 11, 2018, and April 23, 2021, we screened 2867 patients, enrolled 149 patients, and randomly assigned 128 to dexamethasone (n=85) or placebo (n=43). The mean change in dyspnoea NRS intensity from baseline to day 7 (±2 days) was –1·6 (95% CI –2·0 to –1·2) in the dexamethasone group and –1·6 (–2·3 to –0·9) in the placebo group, with no significant between-group difference (mean 0 [95% CI –0·8 to 0·7]; p=0·48). The most common all-cause grade 3–4 adverse events were infections (nine [11%] of 85 patients in the dexamethasone group vs three [7%] of 43 in the placebo group), insomnia (seven [8%] vs one [2%]), and neuropsychiatric symptoms (three [4%] vs none [0%]). Serious adverse events, all resulting in hospital admissions, were reported in 24 (28%) of 85 patients in the dexamethasone group and in three (7%) of 43 patients in the placebo group. No treatment-related deaths occurred in either group. Interpretation: High-dose dexamethasone did not improve dyspnoea 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 dyspnoea. Funding: US National Cancer Institute.
AB - Background: Systemic corticosteroids are commonly prescribed for palliation of dyspnoea in patients with cancer, despite scarce evidence to support their use. We aimed to assess the effect of high-dose dexamethasone versus placebo on cancer-related dyspnoea. Methods: The parallel-group, double-blind, randomised, controlled ABCD (Alleviating Breathlessness in Cancer Patients with Dexamethasone) trial was done at the at the University of Texas MD Anderson Cancer Center and the general oncology clinic at Lyndon B Johnson General Hospital (both in Houston, TX, USA). Ambulatory patients with cancer, aged 18 years or older, and with an average dyspnoea intensity score on an 11-point numerical rating scale (NRS; 0=none, 10=worst) over the past week of 4 or higher were randomly assigned (2:1) to receive dexamethasone 8 mg orally every 12 h for 7 days followed by 4 mg orally every 12 h for 7 days, or matching placebo capsules for 14 days. Pharmacists did permuted block randomisation with a block size of six, and patients were stratified by baseline dyspnoea score (4–6 vs 7–10) and study site. Patients, research staff, and clinicians were masked to group assignment. The primary outcome was change in dyspnoea NRS intensity over the past 24 h from baseline to day 7 (±2 days). Analyses were done by modified intention-to-treat (ie, including all patients who were randomly assigned and started the study treatment, regardless of whether they completed the study). Enrolment was stopped after the second preplanned interim analysis, when the futility criterion was met. This study is registered with ClinicalTrials.gov (NCT03367156) and is now completed. Findings: Between Jan 11, 2018, and April 23, 2021, we screened 2867 patients, enrolled 149 patients, and randomly assigned 128 to dexamethasone (n=85) or placebo (n=43). The mean change in dyspnoea NRS intensity from baseline to day 7 (±2 days) was –1·6 (95% CI –2·0 to –1·2) in the dexamethasone group and –1·6 (–2·3 to –0·9) in the placebo group, with no significant between-group difference (mean 0 [95% CI –0·8 to 0·7]; p=0·48). The most common all-cause grade 3–4 adverse events were infections (nine [11%] of 85 patients in the dexamethasone group vs three [7%] of 43 in the placebo group), insomnia (seven [8%] vs one [2%]), and neuropsychiatric symptoms (three [4%] vs none [0%]). Serious adverse events, all resulting in hospital admissions, were reported in 24 (28%) of 85 patients in the dexamethasone group and in three (7%) of 43 patients in the placebo group. No treatment-related deaths occurred in either group. Interpretation: High-dose dexamethasone did not improve dyspnoea 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 dyspnoea. Funding: US National Cancer Institute.
UR - http://www.scopus.com/inward/record.url?scp=85138795057&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85138795057&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(22)00508-3
DO - 10.1016/S1470-2045(22)00508-3
M3 - Article
C2 - 36087590
AN - SCOPUS:85138795057
SN - 1470-2045
VL - 23
SP - 1321
EP - 1331
JO - The lancet oncology
JF - The lancet oncology
IS - 10
ER -