地塞米松对癌症患者呼吸困难的作用:一项平行组、双盲、随机、对照试验

28 September 2022

Effect of dexamethasone on dyspnoea in patients with cancer (ABCD): a parallel-group, double-blind, randomised, controlled trial

 (Lancet Oncology, IF: 54.433)

Hui D, Puac V, Shelal Z, et al. Effect of dexamethasone on dyspnoea in patients with cancer (ABCD): a parallel-group, double-blind, randomised, controlled trial. The Lancet Oncology 2022;23(10):1321-1331. DOI: 10.1016/s1470-2045(22)00508-3.

Correspondence to: Prof David Hui, Department of Palliative Care, Rehabilitation and Integrative Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. dhui@mdanderson.org

Background 背景

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.

全身糖皮质激素通常用于缓解癌症患者的呼吸困难，尽管缺乏证据支持其使用。我们的目的是评估大剂量地塞米松与安慰剂相比对癌症相关呼吸困难的作用。

Methods 方法

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.

该平行组、双盲、随机、对照ABCD(地塞米松缓解癌症患者呼吸困难)试验在德克萨斯大学MD Anderson癌症中心和Lyndon B Johnson综合医院的普通肿瘤诊所(均位于美国德克萨斯州休斯顿)完成。过去一周年龄在18岁或以上的门诊癌症患者，在11分数值分级量表(NRS;0=无，10=最差)评分4分或以上的患者被随机分配(2:1)接受地塞米松每12小时口服8mg，持续7天，然后每12小时口服4mg，持续7天，或服用相同剂量的安慰剂胶囊，持续14天。药剂师进行随机排列区组随机化，区组大小为6，患者按基线呼吸困难评分(4-6 vs 7-10)和研究地点分层。患者、研究人员和临床医生都不知道分组。主要结局为从基线后24小时内到第7天(±2天)呼吸困难NRS强度的变化。通过修正意向治疗(即包括所有随机分配并开始研究治疗的患者，无论他们是否完成研究)进行分析。在第二次预先计划的中期分析后，当无效标准满足时，停止登记。该研究已注册在ClinicalTrials.gov (NCT03367156)，现在已完成。

Findings 结果

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 dyspnea 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.

在2018年1月11日至2021年4月23日期间，我们筛查了2867名患者，纳入了149名患者，并随机分配128名患者服用地塞米松(n=85)或安慰剂(n=43)。从基线到第7天(±2天)，地塞米松组呼吸困难NRS强度的平均变化为-1.6 (95% CI -2.0到-1.2)，安慰剂组为-1.6(-2.3到-0.9)，组间无显著差异(平均0 [95% CI -0.8到0.7]；p = 0.48)。最常见的全因3-4级不良事件是感染(地塞米松组85例患者中有9例[11%]，安慰剂组43例患者中有3例[7%])、失眠(7例[8%]，1例[2%])和神经精神症状(3例[4%]，0例[0%])。地塞米松组85例患者中有24例(28%)出现严重不良事件，安慰剂组43例患者中有3例(7%)出现严重不良事件，均导致住院。两组均无治疗相关死亡发生。

Interpretation 解释

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.

与安慰剂相比，大剂量地塞米松并不能更有效地改善癌症患者的呼吸困难，并与较高的不良事件发生率相关。这些数据表明，地塞米松不应常规给予未选择的癌症患者缓解呼吸困难。

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