University of Michigan School of Nursing, Room 2151, Ann Arbor, MI 48109, USA.
JAMA. 2013 Apr 3;309(13):1359-67. doi: 10.1001/jama.2013.2813.
There are no known effective treatments for painful chemotherapy-induced peripheral neuropathy.
To determine the effect of duloxetine, 60 mg daily, on average pain severity.
DESIGN, SETTING, AND PATIENTS: Randomized, double-blind, placebo-controlled crossover trial at 8 National Cancer Institute (NCI)-funded cooperative research networks that enrolled 231 patients who were 25 years or older being treated at community and academic settings between April 2008 and March 2011. Study follow-up was completed July 2012. Stratified by chemotherapeutic drug and comorbid pain risk, patients were randomized to receive either duloxetine followed by placebo or placebo followed by duloxetine. Eligibility required that patients have grade 1 or higher sensory neuropathy according to the NCI Common Terminology Criteria for Adverse Events and at least 4 on a scale of 0 to 10, representing average chemotherapy-induced pain, after paclitaxel, other taxane, or oxaliplatin treatment.
The initial treatment consisted of taking 1 capsule daily of either 30 mg of duloxetine or placebo for the first week and 2 capsules of either 30 mg of duloxetine or placebo daily for 4 additional weeks.
The primary hypothesis was that duloxetine would be more effective than placebo in decreasing chemotherapy-induced peripheral neuropathic pain. Pain severity was assessed using the Brief Pain Inventory-Short Form "average pain" item with 0 representing no pain and 10 representing as bad as can be imagined.
Individuals receiving duloxetine as their initial 5-week treatment reported a mean decrease in average pain of 1.06 (95% CI, 0.72-1.40) vs 0.34 (95% CI, 0.01-0.66) among those who received placebo (P = .003; effect size, 0.513). The observed mean difference in the average pain score between duloxetine and placebo was 0.73 (95% CI, 0.26-1.20). Fifty-nine percent of those initially receiving duloxetine vs 38% of those initially receiving placebo reported decreased pain of any amount.
Among patients with painful chemotherapy-induced peripheral neuropathy, the use of duloxetine compared with placebo for 5 weeks resulted in a greater reduction in pain.
clinicaltrials.gov Identifier: NCT00489411.
目前尚无已知有效的治疗方法可用于缓解化疗引起的外周神经痛。
评估度洛西汀（每日 60mg）对平均疼痛严重程度的影响。
设计、地点和患者：本研究为随机、双盲、安慰剂对照交叉试验，在 8 个美国国家癌症研究所（NCI）资助的合作研究网络中开展，共纳入 231 名患者，这些患者年龄均≥25 岁，在社区和学术环境中接受治疗，治疗药物为紫杉醇、其他紫杉烷类或奥沙利铂，研究于 2008 年 4 月至 2011 年 3 月入组，2012 年 7 月完成随访。根据化疗药物和伴发疼痛风险进行分层，患者被随机分配接受度洛西汀或安慰剂治疗。纳入标准为根据 NCI 常见不良事件术语标准评估的 1 级或更高的感觉神经病变，且在接受紫杉醇、其他紫杉烷类或奥沙利铂治疗后，疼痛评分为 0-10 分中的 4 分或以上，代表平均化疗引起的疼痛。
初始治疗为连续 5 周服用 30mg 度洛西汀或安慰剂 1 粒/天，接下来 4 周每日服用 30mg 度洛西汀或安慰剂 2 粒。
主要假设为度洛西汀治疗组在降低化疗引起的周围神经病理性疼痛方面比安慰剂组更有效。疼痛严重程度采用简短疼痛清单-简表“平均疼痛”项目进行评估，0 表示无痛，10 表示疼痛难以想象。
接受度洛西汀初始 5 周治疗的患者平均疼痛评分降低 1.06（95%置信区间：0.72-1.40），而接受安慰剂治疗的患者平均疼痛评分降低 0.34（95%置信区间：0.01-0.66）（P=0.003；效应量为 0.513）。度洛西汀组与安慰剂组平均疼痛评分的差值为 0.73（95%置信区间：0.26-1.20）。与初始接受安慰剂治疗的患者相比，初始接受度洛西汀治疗的患者中 59%的患者报告疼痛减轻了任何程度，而初始接受安慰剂治疗的患者中 38%的患者报告疼痛减轻了任何程度。
在患有化疗引起的周围神经病理性疼痛的患者中，与安慰剂相比，使用度洛西汀治疗 5 周可显著降低疼痛程度。
clinicaltrials.gov 标识符：NCT00489411。
