Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir
Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir
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DOI：
10.1172/jci68730
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发表时间：
2014-01-01
影响因子：
15.9
通讯作者：
Batteux, Frederic
中科院分区：
文献类型：
--
作者：
Coriat, Romain;Alexandre, Jerome;Batteux, Frederic
背景。大多数接受铂类化疗药物奥沙利铂的患者会出现周围神经毒性。由于这种神经毒性涉及 ROS 的产生，因此我们研究了锰福地吡（mangafodipir）的功效，这种分子具有抗氧化特性，并被批准用作 MRI 对比增强剂。方法。在奥沙利铂治疗后的小鼠中检查了锰福地吡的作用。监测神经毒性、轴突髓鞘形成和高级氧化蛋白产物（AOPP）。此外，我们在一项 II 期研究中招募了 23 名患有≥2 级奥沙利铂诱发神经病变的癌症患者，其中 22 名患者接受静脉注射。锰福地吡继奥沙利铂之后。监测奥沙利铂和锰福地吡长达 8 个周期的神经病理效应。结果。锰福地吡可预防运动和感觉功能障碍以及脱髓鞘病变的形成。在小鼠中，锰福地吡治疗 4 周后，血清 AOPP 下降。在接受奥沙利铂和锰加福地吡治疗的患者中，77% 的患者神经病变在 4 个周期后得到改善或稳定。 8 个周期后，7 名患者中有 6 名的神经毒性降至≥ 2 级。入组前，患者平均接受 880 +/- 239 mg/m(2) 奥沙利铂。尽管先前存在神经病变，接受曼加福地吡治疗的患者仍能耐受额外剂量的 458 +/- 207 mg/m(2) 奥沙利铂。 Mangafodipir 应答者管理的奥沙利铂累积剂量为 1,426 +/- 204 mg/m(2)。与无反应者相比，有反应者的血清 AOPP 较低。结论。我们的研究表明，锰福地吡可以预防和/或缓解奥沙利铂引起的癌症患者神经病变。
Background. The majority of patients receiving the platinum-based chemotherapy drug oxaliplatin develop peripheral neurotoxicity. Because this neurotoxicity involves ROS production, we investigated the efficacy of mangafodipir, a molecule that has antioxidant properties and is approved for use as an MRI contrast enhancer.Methods. The effects of mangafodipir were examined in mice following treatment with oxaliplatin. Neurotoxicity, axon myelination, and advanced oxidized protein products (AOPPs) were monitored. In addition, we enrolled 23 cancer patients with grade >= 2 oxaliplatin-induced neuropathy in a phase II study, with 22 patients receiving i.v. mangafodipir following oxaliplatin. Neuropathic effects were monitored for up to 8 cycles of oxaliplatin and mangafodipir.Results. Mangafodipir prevented motor and sensory dysfunction and demyelinating lesion formation. In mice, serum AOPPs decreased after 4 weeks of mangafodipir treatment. In 77% of patients treated with oxaliplatin and mangafodipir, neuropathy improved or stabilized after 4 cycles. After 8 cycles, neurotoxicity was downgraded to grade >= 2 in 6 of 7 patients. Prior to enrollment, patients received an average of 880 +/- 239 mg/m(2) oxaliplatin. Patients treated with mangafodipir tolerated an additional dose of 458 +/- 207 mg/m(2) oxaliplatin despite preexisting neuropathy. Mangafodipir responders managed a cumulative dose of 1,426 +/- 204 mg/m(2) oxaliplatin. Serum AOPPs were lower in responders compared with those in nonresponders.Conclusion. Our study suggests that mangafodipir can prevent and/or relieve oxaliplatin-induced neuropathy in cancer patients.