Additive Duloxetine for Cancer-Related Neuropathic Pain Nonresponsive or Intolerant to Opioid-Pregabalin Therapy: A Randomized Controlled Trial (JORTC-PAL08).
Additive Duloxetine for Cancer-Related Neuropathic Pain Nonresponsive or Intolerant to Opioid-Pregabalin Therapy: A Randomized Controlled Trial (JORTC-PAL08).
复制标题
添加度洛西汀治疗对阿片类药物普瑞巴林治疗无反应或不耐受的癌症相关神经性疼痛：随机对照试验 (JORTC-PAL08)。
DOI：
10.1016/j.jpainsymman.2019.06.020
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Yamaguchi
中科院分区：
文献类型：
--
作者：
Matsuoka H;Iwase S;Miyaji T;Kawaguchi T;Ariyoshi K;Oyamada S;Satomi E;Ishiki H;Hasuo H;Sakuma H;Tokoro A;Shinomiya T;Otani H;Ohtake Y;Tsukuura H;Matsumoto Y;Hasegawa Y;Kataoka Y;Otsuka M;Sakai K;Matsuda Y;Morita T;Koyama A;Yamaguchi
背景虽然阿片类药物和普瑞巴林被广泛用于癌症相关的神经性疼痛（CNP），但没有临床试验来确定当阿片类药物-普瑞巴林联合治疗失败时哪些药物是有效的。安慰剂对照试验在日本的12个专业姑息治疗服务机构进行。在过去24小时内CNP平均疼痛评分（简明疼痛量表[BPI]-第5项）≥ 4且对阿片类药物-普瑞巴林联合治疗无应答或不耐受的患者符合资格。排除化疗诱导的周围神经病变患者。患者接受度洛塞汀20 mg/天滴定至40 mg/天或安慰剂给药，持续10天。主要终点为第10天的BPI-项目5。应答者分析测量患者的比例与30%和50%的疼痛reduces.ResultsSeventy例患者参加。完整病例分析显示，D组第10天的平均BPI-项目5为4.03，P组为4.88（P =0.053）。基线观察值结转分析显示，D组和P组第10天的平均BPI-项目5分别为4.06和4.91（P =0.048）。D组44.1%（n= 15）的患者报告了具有临床意义的疼痛改善（≥30%），P组18.2%（n= 6）（P =0.02）; D组和P组分别有32.4%（n= 11）和3.0%（n= 1）的患者，报告疼痛减轻≥ 50%（P =0.002）。结论在阿片-普瑞巴林治疗基础上加用度洛西汀可能对缓解难治性CNP有临床益处。需要进一步的研究来得出加入度洛沙汀的有效性。
ContextAlthough opioids and pregabalin are widely used for cancer-related neuropathic pain (CNP), no clinical trials exist to determine which medications are effective when an opioid-pregabalin combination therapy fails.ObjectivesWe investigated the efficacy of duloxetine for CNP nonresponsive or intolerant to opioid-pregabalin combination therapy.MethodsA multicenter, randomized, double-blind, placebo-controlled trial was performed at 12 specialized palliative care services in Japan. Patients with CNP average pain scores (Brief Pain Inventory [BPI]–Item 5) ≥ 4 in the previous 24 hours and nonresponsive or intolerant to opioid-pregabalin combination therapy were eligible. Patients with chemotherapy-induced peripheral neuropathies were excluded. Patients were administered duloxetine 20 mg/day titrated to 40 mg/day or placebo for 10 days. The primary endpoint was BPI-Item 5 on Day 10. Responder analysis measured proportions of patients with 30% and 50% pain decreases.ResultsSeventy patients were enrolled. Complete case analysis revealed mean BPI-Item 5 on Day 10 of 4.03 for Group D vs. 4.88 for Group P (P =0.053). Baseline observation carried forward analysis revealed mean BPI-Item 5 on Day 10 of 4.06 and 4.91 for Groups D and P, respectively (P =0.048). Clinically meaningful pain improvement (≥30%) was reported by 44.1% (n= 15) of patients in Group D vs. 18.2% (n= 6) in Group P (P =0.02); 32.4% (n= 11) vs. 3.0% (n= 1) of patients in Groups D and P, respectively, reported pain reduction ≥ 50% (P =0.002).ConclusionAdding duloxetine to opioid-pregabalin therapy might have clinical benefit in alleviating refractory CNP. Further studies are needed to conclude the efficacy of adding duloxetine.