Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark.
BMC Cancer. 2024 Feb 3;24(1):168. doi: 10.1186/s12885-024-11856-z.
Oxaliplatin-induced peripheral neuropathy (OIPN) in general and painful OIPN in particular is a debilitating late effect that severely affects cancer survivors' quality of life and causes premature cessation of potentially lifesaving treatment. No preventive treatments and no effective treatment for chronic OIPN exist despite many attempts. One of several suggested mechanisms includes neuroinflammation as a contributing factor to OIPN. Fish oil containing long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFAs) are precursors to specialized proresolving mediators that mediate the resolution of inflammation. Our primary hypothesis is that a high supplementation of n-3 LCPUFAs will lower the prevalence and severity of OIPN.
The OxaNeuro project is an investigator-initiated, multicenter, double-blinded, randomized, placebo-controlled clinical study. We will include 120 patients eligible to receive adjuvant oxaliplatin after colorectal cancer surgery. Patients will receive fish oil capsules containing n-3 LCPUFAs or corn oil daily for 8 months. The primary endpoint is the prevalence of OIPN at 8 months defined as relevant symptoms, including one of the following: abnormal nerve conduction screening, abnormal vibration threshold test, abnormal skin biopsy, or abnormal pinprick test. Additional endpoints include the intensity and severity of OIPN-related neuropathic pain, patient-reported OIPN symptoms, quality of life, mental health symptoms, body composition, and cognitive evaluation. Furthermore, we will evaluate inflammatory biomarkers in blood samples and skin biopsies, including the potential OIPN biomarker neurofilament light protein (NfL) which will be measured before each cycle of chemotherapy.
If readily available fish oil supplementation alleviates OIPN prevalence and severity, it will significantly improve the lives of both cancer survivors and palliative cancer patients receiving oxaliplatin; it will improve their quality of life, optimize chemotherapeutic treatment plans by lowering the need for dose reduction or premature cessation, and potentially increase survival.
ClinicalTrial.gov identifier: NCT05404230 Protocol version: 1.2, April 25. 2023.
奥沙利铂引起的周围神经病变（OIPN），特别是痛性 OIPN，是一种使人虚弱的晚期效应，严重影响癌症幸存者的生活质量，并导致潜在的救命治疗过早停止。尽管进行了多次尝试，但仍没有预防治疗和治疗慢性 OIPN 的有效方法。几种建议的机制之一包括神经炎症是 OIPN 的一个促成因素。富含长链 n-3 多不饱和脂肪酸（n-3 LCPUFAs）的鱼油是专门的促解决介质的前体，可介导炎症的解决。我们的主要假设是，n-3 LCPUFAs 的高补充将降低 OIPN 的患病率和严重程度。
OxaNeuro 项目是一项由研究者发起的、多中心、双盲、随机、安慰剂对照的临床研究。我们将纳入 120 名有资格在结直肠癌手术后接受辅助奥沙利铂治疗的患者。患者将每天服用含 n-3 LCPUFAs 的鱼油胶囊或玉米油，持续 8 个月。主要终点是 8 个月时 OIPN 的患病率，定义为相关症状，包括以下一种：异常神经传导筛查、异常振动阈值测试、异常皮肤活检或异常刺痛测试。其他终点包括 OIPN 相关神经性疼痛的强度和严重程度、患者报告的 OIPN 症状、生活质量、心理健康症状、身体成分和认知评估。此外，我们将评估血液样本和皮肤活检中的炎症生物标志物，包括神经丝轻蛋白（NfL），这是一种潜在的 OIPN 生物标志物，将在每个化疗周期前进行测量。
如果易于获得的鱼油补充剂能减轻 OIPN 的患病率和严重程度，它将显著改善接受奥沙利铂治疗的癌症幸存者和姑息性癌症患者的生活；它将提高他们的生活质量，通过降低减少剂量或过早停止治疗的需要，优化化疗治疗计划，并有可能提高生存率。
ClinicalTrials.gov 标识符：NCT05404230 方案版本：1.2，2023 年 4 月 25 日。
