Dexamethasone in the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases: a double-blind, randomised placebo-controlled, phase 3 trial
Dexamethasone in the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases: a double-blind, randomised placebo-controlled, phase 3 trial
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DOI：
10.1016/s1470-2045(15)00199-0
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发表时间：
2015-11-01
期刊：
影响因子：
51.1
通讯作者：
Wong, Rebecca K. S.
中科院分区：
文献类型：
--
作者：
Chow, Edward;Meyer, Ralph M.;Wong, Rebecca K. S.
背景姑息性放疗后疼痛发作，地塞米松已显示出预防这种发作的潜力。我们的目的是比较地塞米松与安慰剂在减少疼痛发作发生率方面的疗效。方法在这项双盲、随机、安慰剂对照的3期试验中，来自23个加拿大中心的患者被随机分配（1：1），采用基于网络的系统和最小化算法，在放射治疗开始前至少1小时口服两片4 mg地塞米松片剂或两片安慰剂片剂（骨转移单次8戈伊剂量;第0天），然后在放疗后每天给药4天（第1-4天）。如果患者患有与临床疼痛区域对应的非血液学恶性肿瘤和骨转移（或转移瘤），则患者合格。患者在治疗前和放射治疗后10天每天报告他们的最差疼痛评分和阿片类镇痛药摄入量。他们在基线和放射治疗后第10天和第42天完成了欧洲癌症研究和治疗组织（EORTC）生活质量QLQ-C15-PAL、骨转移模块（EORTC QLQ-BM 22）和地塞米松症状问卷。疼痛发作定义为最差疼痛评分在0-10量表上至少增加2分，且镇痛剂摄入量未减少，或镇痛剂摄入量增加25%或以上，且第0-10天最差疼痛评分未降低，随后恢复至基线水平或更低。疼痛发作发生率的主要分析是按意向治疗进行的（缺失主要数据的患者被归类为疼痛发作）。本研究在ClinicalTrials.gov注册，编号NCT 01248585，并已完成。随机分配至地塞米松组的148例患者中有39例（26%）和安慰剂组的150例患者中有53例（35%）出现疼痛发作（差异8.9%，95%置信下限0.0，单侧p=0.05）。地塞米松组发生了2例3级和1例4级生化高血糖事件（无已知临床效应），而安慰剂组未发生。最常见的不良反应是骨痛（61/147 [41%] vs 68/143 [48%]），疲劳（58/147例[39%] vs 49/143例[34%]），便秘（47/147例[32%] vs 37/143例[26%]）和恶心（34/147 [23%] vs 34/143 [24%]），其中大多数为轻度1级或2级。解释地塞米松在治疗疼痛性骨转移中减少放射引起的疼痛发作。
Background Pain flare occurs after palliative radiotherapy, and dexamethasone has shown potential for prevention of such flare. We aimed to compare the efficacy of dexamethasone with that of placebo in terms of reduction of incidence of pain flare.Methods In this double-blind, randomised, placebo-controlled phase 3 trial, patients from 23 Canadian centres were randomly allocated (1:1) with a web-based system and minimisation algorithm to receive either two 4 mg dexamethasone tablets or two placebo tablets taken orally at least 1 h before the start of radiation treatment (a single 8 Gy dose to bone metastases; day 0) and then every day for 4 days after radiotherapy (days 1-4). Patients were eligible if they had a non-haematological malignancy and bone metastasis (or metastases) corresponding to the clinically painful area or areas. Patients reported their worst pain scores and opioid analgesic intake before treatment and daily for 10 days after radiation treatment. They completed the European Organisation for Research and Treatment of Cancer (EORTC) quality of life QLQ-C15-PAL, the bone metastases module (EORTC QLQ-BM22), and the Dexamethasone Symptom Questionnaire at baseline, and at days 10 and 42 after radiation treatment. Pain flare was defined as at least a two-point increase on a scale of 0-10 in the worst pain score with no decrease in analgesic intake, or a 25% or greater increase in analgesic intake with no decrease in the worst pain score from days 0-10, followed by a return to baseline levels or below. Primary analysis of incidence of pain flare was by intention-to-treat (patients with missing primary data were classified as having pain flare). This study is registered with ClinicalTrials.gov, number NCT01248585, and is completed.Findings Between May 30, 2011, and Dec 11, 2014, 298 patients were enrolled. 39 (26%) of 148 patients randomly allocated to the dexamethasone group and 53 (35%) of 150 patients in the placebo group had a pain flare (difference 8.9%, lower 95% confidence bound 0.0, one-sided p=0.05). Two grade 3 and one grade 4 biochemical hyperglycaemic events occurred in the dexamethasone group (without known clinical effects) compared with none in the placebo group. The most common adverse events were bone pain (61 [41%] of 147 vs 68 [48%] of 143), fatigue (58 [39%] of 147 vs 49 [34%] of 143), constipation (47 [32%] of 147 vs 37 [26%] of 143), and nausea (34 [23%] of 147 vs 34 [24%] of 143), most of which were mild grade 1 or 2.Interpretation Dexamethasone reduces radiation-induced pain flare in the treatment of painful bone metastases.