Martin Elodie, Morel Véronique, Joly Dominique, Villatte Christine, Delage Noémie, Dubray Claude, Pereira Bruno, Pickering Gisèle
Clermont Université, Laboratoire de Pharmacologie, Faculté de médecine, F-63001 Clermont-Ferrand, France; Inserm, CIC 1405, UMR Neurodol 1107, F-63003 Clermont-Ferrand, France.
Inserm, CIC 1405, UMR Neurodol 1107, F-63003 Clermont-Ferrand, France; CHU Clermont-Ferrand, Centre de Pharmacologie Clinique, F-63003 Clermont-Ferrand, France.
Contemp Clin Trials. 2015 Mar;41:146-51. doi: 10.1016/j.cct.2015.01.012. Epub 2015 Jan 28.
Anti-cancer chemotherapy often induces peripheral neuropathy and consequent cognitive and quality of life impairment. Guidelines recommend antiepileptics or antidepressants but their efficacy is limited.Dextromethorphan, a N-methyl-D-aspartate receptor antagonist, has shown its efficacy in painful diabetic neuropathy and in post-operative pain but has not been studied in chemotherapy-induced peripheral neuropathy. This clinical trial evaluates the effect of dextromethorphan on pain, cognition and quality of life in patients who suffer from neuropathic pain induced by chemotherapy for breast cancer. It also assesses the impact of dextromethorphan genetic polymorphism on analgesia.
This trial is a randomized, placebo-controlled, double-blind clinical study in two parallel groups (NCT02271893). It includes 40 breast cancer patients suffering from chemotherapy-induced peripheral neuropathy. They are randomly allocated to dextromethorphan (maximal dose 90 mg/day) or placebo for 4 weeks. The primary endpoint is pain intensity measured after 4 weeks of treatment on a (0-10) Numeric Pain Rating Scale. Secondary outcomes include assessment of neuropathic pain, cognitive function, anxiety/depression, sleep and quality of life. Data analysis is performed using mixed models and the tests are two-sided, with a type I error set at α=0.05.
Considering the poor efficacy of available drugs in chemotherapy-induced neuropathic pain, dextromethorphan may be a valuable therapeutic option. Pharmacogenetics may provide predictive factors of dextromethorphan response in patients suffering from breast cancer.
抗癌化疗常诱发周围神经病变，进而导致认知及生活质量受损。指南推荐使用抗癫痫药或抗抑郁药，但其疗效有限。右美沙芬作为一种N-甲基-D-天冬氨酸受体拮抗剂，已在糖尿病性疼痛性神经病变及术后疼痛中显示出疗效，但尚未在化疗诱发的周围神经病变中进行研究。本临床试验评估右美沙芬对乳腺癌化疗所致神经病理性疼痛患者的疼痛、认知及生活质量的影响。同时还评估右美沙芬基因多态性对镇痛效果的影响。
本试验为一项随机、安慰剂对照、双盲的平行组临床研究（NCT02271893）。纳入40例患有化疗诱发周围神经病变的乳腺癌患者。将他们随机分配至右美沙芬组（最大剂量90mg/天）或安慰剂组，治疗4周。主要终点为治疗4周后采用（0 - 10）数字疼痛评分量表测量的疼痛强度。次要结局包括对神经病理性疼痛、认知功能、焦虑/抑郁、睡眠及生活质量的评估。数据分析采用混合模型，检验为双侧检验，I型错误设定为α = 0.05。
鉴于现有药物对化疗诱发神经病理性疼痛的疗效不佳，右美沙芬可能是一种有价值的治疗选择。药物遗传学可能为乳腺癌患者右美沙芬反应提供预测因素。
