Velasco Roser, Besora Sarah, Argyriou Andreas A, Santos Cristina, Sala Rosó, Izquierdo Cristina, Simó Marta, Gil-Gil Miguel, Pardo Beatriz, Jiménez Laura, Clapés Victoria, Calvo Mariona, Palmero Ramón, Bruna Jordi
Neuro-Oncology Unit, Department of Neurology, Hospital Universitari de Bellvitge-ICO L'Hospitalet, IDIBELL, Barcelona.
Department of Cell Biology, Physiology and Immunology, Institute of Neurosciences, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra.
Anticancer Drugs. 2021 Jan 1;32(1):88-94. doi: 10.1097/CAD.0000000000001005.
The objective of this observational study was to evaluate the efficacy and safety of duloxetine in a cohort of 100 cancer survivors with chemotherapy-induced peripheral neurotoxicity (CIPN). CIPN was graded employing the TNSc and the NCI-CTCv4. The Patient Global Impression of Change (PGIC) scale measured the efficacy of duloxetine (1: no benefit; to 7: excellent response). A clinically meaningful response was considered a PGIC > 4. Median age was 62 (29-81) years and 42% were male. CIPN was graded as grades 1, 2 and 3 in 20, 66, and 14% of patients, respectively. Median time to duloxetine initiation was 6 (1-63) months after chemotherapy. Fifty-seven patients early dropped out from duloxetine, due to lack of efficacy (20%) or side effects (37%). Male patients more frequently discontinued duloxetine due to lack of efficacy (35.7 vs. 8.6% P = 0.001). PGIC scores were higher in female patients (4 vs. 1, P = 0.001), taxane-treated patients (4 vs. 1, P = 0.042) and with short-lasting (<6 months) CIPN (4 vs. 1, P = 0.008). Patients with long-lasting CIPN had a higher rate of adverse events (47 vs. 27%, P = 0.038) and discontinuation (54.8 vs. 45.1%, P = 0.023). In the multivariate analysis, female gender and short-lasting CIPN were independently associated with a favorable response to duloxetine. Low tolerability, male gender, and long-lasting CIPN significantly limited duloxetine use in daily practice setting. A minority of cancer survivors with CIPN treated with duloxetine had a meaningful CIPN improvement, and tolerability was overall low. Female gender and short-term CIPN were independently associated with a favorable response to duloxetine.
这项观察性研究的目的是评估度洛西汀在100名患有化疗引起的周围神经毒性（CIPN）的癌症幸存者队列中的疗效和安全性。采用TNSc和NCI-CTCv4对CIPN进行分级。患者总体变化印象（PGIC）量表衡量度洛西汀的疗效（1：无益处；至7：极佳反应）。具有临床意义的反应被认为是PGIC＞4。中位年龄为62（29 - 81）岁，42%为男性。分别有20%、66%和14%的患者CIPN被分级为1级、2级和3级。开始使用度洛西汀的中位时间是化疗后6（1 - 63）个月。57名患者因疗效不佳（20%）或副作用（37%）提前停用度洛西汀。男性患者因疗效不佳更频繁地停用度洛西汀（35.7%对8.6%，P = 0.001）。女性患者、接受紫杉烷治疗的患者以及患有短期（<6个月）CIPN的患者PGIC评分更高（4对1，P = 0.001；4对1，P = 0.042；4对1，P = 0.008）。患有长期CIPN的患者不良事件发生率更高（47%对27%，P = 0.038），停药率也更高（54.8%对45.1%，P = 0.023）。在多变量分析中，女性性别和短期CIPN与度洛西汀的良好反应独立相关。在日常实践中，低耐受性、男性性别和长期CIPN显著限制了度洛西汀的使用。少数接受度洛西汀治疗的患有CIPN的癌症幸存者CIPN有有意义的改善，且总体耐受性较低。女性性别和短期CIPN与度洛西汀的良好反应独立相关。
