Department of Palliative Care, Rehabilitation and Integrative Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of General Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Palliative Care, Rehabilitation and Integrative Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lancet Oncol. 2022 Oct;23(10):1321-1331. doi: 10.1016/S1470-2045(22)00508-3. Epub 2022 Sep 7.
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.
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.
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.
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.
US National Cancer Institute.
尽管缺乏支持使用的证据，但全身皮质类固醇类药物仍常被用于缓解癌症患者的呼吸困难，尽管缺乏支持使用的证据。我们旨在评估高剂量地塞米松与安慰剂对癌症相关呼吸困难的影响。
在德克萨斯大学 MD 安德森癌症中心和林登·B·约翰逊综合医院（均位于美国得克萨斯州休斯顿市）的普通肿瘤诊所，进行了这项平行分组、双盲、随机、对照的 ABCD（用地塞米松减轻癌症患者呼吸困难）试验。纳入年龄在 18 岁及以上、过去一周平均呼吸困难数字评分量表（NRS；0=无，10=最严重）为 4 或更高的、有活动能力的癌症患者，将其随机（2:1）分配至接受地塞米松 8 mg 口服，每 12 h 一次，共 7 天，随后 4 mg 口服，每 12 h 一次，共 7 天，或接受匹配的安慰剂胶囊，共 14 天。药剂师采用按区组大小为 6 的区组随机化方法进行分组，根据基线呼吸困难评分（4-6 与 7-10）和研究地点对患者进行分层。患者、研究人员和临床医生均对分组情况设盲。主要结局是从基线到第 7 天（±2 天）的过去 24 小时呼吸困难 NRS 强度的变化。采用改良意向治疗（即包括所有随机分配并开始研究治疗的患者，无论其是否完成研究）进行分析。在第二个预先计划的中期分析达到无效标准后，停止了入组。本研究在 ClinicalTrials.gov 注册（NCT03367156），现已完成。
2018 年 1 月 11 日至 2021 年 4 月 23 日，我们筛选了 2867 名患者，纳入了 149 名患者，并随机分配了 128 名患者至地塞米松组（n=85）或安慰剂组（n=43）。从基线到第 7 天（±2 天）的呼吸困难 NRS 强度变化，地塞米松组为-1·6（95%CI -2·0 至 -1·2），安慰剂组为-1·6（-2·3 至 -0·9），两组间无显著差异（平均差值 0 [95%CI -0·8 至 0·7]；p=0·48）。最常见的所有原因的 3-4 级不良事件是感染（地塞米松组 85 名患者中有 9 例[11%]，安慰剂组 43 名患者中有 3 例[7%]）、失眠（地塞米松组 8 名[8%]，安慰剂组 1 名[2%]）和神经精神症状（地塞米松组 3 名[4%]，安慰剂组无[0%]）。地塞米松组有 24 名（28%）患者和安慰剂组有 3 名（7%）患者报告了严重不良事件，均导致住院治疗。两组均未发生与治疗相关的死亡。
高剂量地塞米松并不能比安慰剂更有效地改善癌症患者的呼吸困难，且与更高的不良事件发生率相关。这些数据表明，地塞米松不应常规用于缓解癌症患者的呼吸困难。
美国国立癌症研究所。
