Tetrodotoxin for moderate to severe cancer pain: A randomized, double blind, parallel design Multicenter study
Tetrodotoxin for moderate to severe cancer pain: A randomized, double blind, parallel design Multicenter study
复制标题
DOI：
10.1016/j.jpainsymman.2007.05.011
复制
发表时间：
2008-04-01
影响因子：
4.7
通讯作者：
Ngoc, Anh Ho
中科院分区：
文献类型：
--
作者：
Hagen, Neil A.;du Souich, Patrick;Ngoc, Anh Ho
癌痛是一个严重的公共卫生问题，需要更有效的治疗方法。本研究评估了河豚毒素（一种高选择性钠通道阻滞剂）的镇痛活性。这项针对皮下河鲀毒素的随机、安慰剂对照、平行设计研究涉及加拿大 22 个中心，研究对象是尽管接受了最佳治疗但仍持续存在中度或重度癌症疼痛的患者。该设计要求在第 1-4 天皮下注射河豚毒素，观察期为第 15 天或更长时间。所有患者都可以参加开放标签扩展疗效和安全性试验。主要终点是每个治疗组中镇痛反应者的比例。 82 名患者被随机分组，其中 77 名患者的结果可供分析。根据主要终点（疼痛强度差异），积极治疗组中出现更多反应者的非统计显着趋势。然而，次要终点的分析和探索性事后分析表明可能存在有效的镇痛剂。如果使用复合终点，包括疼痛水平下降或阿片类药物剂量下降，加上生活质量的改善，就会产生效果。大多数患者在每次治疗后约一小时内描述了短暂的口周刺痛或其他轻微的感觉现象。恶心和其他毒性通常是轻微的，但一名患者经历了严重的不良事件，躯干和步态共济失调。该试验表明河豚毒素可能会缓解大部分患者的中度至重度难治性癌症疼痛，并且通常会在治疗后持续很长时间，但需要使用复合主要终点进行进一步研究。
Cancer pain is a serious public health issue and more effective treatments are needed. This study evaluates the analgesic activity of tetrodotoxin, a highly selective sodium channel blocker. This randomized, placebo-controlled, parallel design study of subcutaneous tetrodotoxin, in patients with moderate or severe unrelieved cancer pain persisting despite best available treatment, involved 22 centers across Canada. The design called for tetrodotoxin administered subcutaneously over Days 1-4 with a period of observation to Day 15 or longer. All patients could enroll into an open-label extension efficacy and safety trial. The primary endpoint was the proportion of analgesic responders in each treatment arm. Eighty-two patients were randomized, and results on 77 were available for analysis. There was a nonstatistically significant trend toward more responders in the active treatment arm based on the primary endpoint (pain intensity difference). However, analysis of secondary endpoints, and an exploratory post hoc analysis, suggested there may be a robust analgesic. effect if a composite endpoint is used, including either fall in pain level, or fall in opioid dose, plus improvement in quality of life. Most patients described transient perioral tingling or other mild sensory phenomena within about an hour of each treatment. Nausea and other toxicities were generally mild, but one patient experienced a serious, adverse event, truncal and gait ataxia. This trial suggests tetrodotoxin may potentially relieve moderate to severe, treatment-resistant cancer pain in a large proportion of patients, and often for prolonged periods following treatment, but further study is warranted using a composite primary endpoint.