An open-label, multi-dose efficacy and safety study of intramuscular tetrodotoxin in patients with severe cancer-related pain
An open-label, multi-dose efficacy and safety study of intramuscular tetrodotoxin in patients with severe cancer-related pain
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DOI：
10.1016/j.jpainsymman.2006.11.008
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发表时间：
2007-08-01
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.;Fisher, Kim M.;Ngoc, Anh Ho
癌症疼痛是一个普遍而严重的公共卫生问题，需要更有效的治疗方法。本研究评估河豚毒素的镇痛活性，一种高选择性钠通道阻滞剂，在癌症疼痛。一项开放标签、多中心、剂量递增的IIa期肌肉注射河豚毒素研究在严重、未缓解的癌性疼痛患者中进行。该研究设计要求对住院患者进行6次递增剂量的肌内河豚毒素注射，为期4天的治疗期，每个连续剂量水平有6名患者入组。24例患者接受31个疗程的治疗，剂量范围为每天13至90毫克，分次给药，为期4天。大多数患者在每次治疗约一小时内描述短暂的口周刺痛或外部轻度感觉现象。恶心和其他毒性一般轻微，但两名患者出现了严重的不良事件，躯干肛门步态共济失调，这一不良事件随着损失而消失。31项治疗中有17项导致临床意义上的疼痛强度减轻，疼痛缓解持续长达两周或更长时间。2例患者因麻醉同时止痛而服用阿片类药物。躯体疼痛、内脏疼痛或神经性疼痛都有反应，但无法预测哪些患者更有可能产生镇痛效果。河豚毒素总体是安全的。它有效地缓解了大多数患者的严重的、难治性的癌症疼痛，并且通常在治疗后持续很长时间。它可能具有一种新的镇痛作用机制。值得进一步研究。
Cancer pain is a prevalent and serious public health issue, and more effective treatments are needed. This study evaluates the analgesic activity of tetrodotoxin, a highly selective sodium channel blocker, in cancer pain. A Phase IIa, open-label, multicenter, dose-escalation study of intramuscular tetrodotoxin was conducted in patients with severe, unrelieved cancer pain. The study design called for six ascending dose levels of intramuscular tetrodotoxin, administered over a four-day treatment period in hospitalized patients, with six patients to be enrolled within each successive dose level. Twenty-four patients underwent 31 courses of treatment at doses ranging from 13 to 90 mu g daily, administered in divided doses, over four days. Most patients described transient perioral tingling or outer mild sensory phenomena within about an hour of each treatment. Nausea and other toxicities were generally mild, but two patients experienced a serious adverse event, truncal anal gait ataxia, that resolved over loss. Seventeen of 31 treatments resulted in clinically meaningful reductions in pain intensity, and relief of pain persisted for up to two weeks or longer. Two patients had opioids held due to narcosis concurrent with relief of pain. Somatic, visceral, or neuropathic pain could all respond, but it was not, possible to predict which patients were more likely to have an analgesic effect. Tetrodotoxin was overall safe. It effectively relieved severe, treatment-resistant cancer pain in the majority of patients and often for prolonged periods after treatment. It may have a novel mechanism of analgesic effect. Further study is warranted.