Purpose Adherence to aromatase inhibitor (AI) therapy for early-stage breast cancer is limited by AI-associated musculoskeletal symptoms (AIMSS). Duloxetine is US Food and Drug Administration approved for treatment of multiple chronic pain disorders. We hypothesized that treatment of AIMSS with duloxetine would improve average joint pain compared with placebo. Methods This randomized, double-blind, phase III trial included AI-treated postmenopausal women with early-stage breast cancer and who had average joint pain score of ≥ 4 out of 10 that developed or worsened since AI therapy initiation. Patients were randomly assigned 1:1 to duloxetine or placebo for 13 weeks. The primary end point was average joint pain through 12 weeks, examined using multivariable linear mixed models, adjusted for stratification factors (baseline pain score of 4 to 6 v 7 to 10 and prior taxane use). Clinically significant change in average pain was defined as a ≥ 2-point decrease from baseline. Results Of 299 enrolled patients, 127 patients treated with duloxetine and 128 who received placebo were evaluable for the primary analysis. By 12 weeks, the average joint pain score was 0.82 points lower for patients who received duloxetine compared with those who received placebo (95% CI, -1.24 to -0.40; P = .0002). Similar patterns were observed for worst joint pain, joint stiffness, pain interference, and functioning. Rates of adverse events of any grade were higher in the duloxetine-treated group (78% v 50%); rates of grade 3 adverse events were similar. Conclusion Results of treatment with duloxetine for AIMSS were superior to those of placebo among women with early-stage breast cancer, although it resulted in more frequent low-grade toxicities.

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度洛西汀与安慰剂治疗早期乳腺癌芳香酶抑制剂相关关节痛的随机、多中心、安慰剂对照临床试验：SWOG S1202

目的 早期乳腺癌对芳香化酶抑制剂 (AI) 治疗的依从性受到 AI 相关肌肉骨骼症状 (AIMSS) 的限制。度洛西汀被美国食品和药物管理局批准用于治疗多种慢性疼痛疾病。我们假设与安慰剂相比，度洛西汀治疗 AIMSS 会改善平均关节疼痛。方法 这项随机、双盲、III 期试验纳入了接受 AI 治疗的绝经后早期乳腺癌女性，她们的平均关节疼痛评分为 ≥ 4（十分之四），自 AI 治疗开始后出现或恶化。患者以 1:1 的比例随机分配至度洛西汀组或安慰剂组，为期 13 周。主要终点是 12 周内的平均关节疼痛，使用多变量线性混合模型进行检查，调整分层因素（基线疼痛评分为 4 至 6 v 7 至 10 和先前紫杉烷使用）。平均疼痛的临床显着变化被定义为从基线下降 ≥ 2 点。结果 在 299 名入组患者中，127 名接受度洛西汀治疗的患者和 128 名接受安慰剂治疗的患者可用于初步分析。到 12 周时，度洛西汀组的平均关节疼痛评分比安慰剂组低 0.82 分（95% CI，-1.24 至 -0.40；P = .0002）。对于最严重的关节疼痛、关节僵硬、疼痛干扰和功能，观察到类似的模式。度洛西汀治疗组任何级别的不良事件发生率均较高（78% 对 50%）；3 级不良事件的发生率相似。