【作者】 郑宇；

【导师】 潘宏铭；

【作者基本信息】 浙江大学 ， 肿瘤学， 2007， 硕士

【摘要】 奥沙利铂是第三代铂类抗癌药物，体内外试验显示对多种肿瘤细胞株有抑制作用，包括对顺铂和卡铂耐药的细胞株。目前在结直肠癌、胃癌、肺癌的治疗中得到了广泛应用。神经毒性是奥沙利铂的剂量限制性毒性，其产生机制与奥沙利铂通过代谢产物草酸盐对钙离子的螯合作用，来改变神经元的电压依赖的钠离子通道有关。本研究通过钙和镁作为草酸盐的螯合剂来预防奥沙利铂的神经毒性。在本研究中，入选的47例患者均接受含奥沙利铂的方案化疗。随机将47例患者分为A、B两组，A组(试验组)为硫酸镁+葡萄糖酸钙+化疗组，共24例。B组(对照组)为单用化疗组，共23例。对照组单用化疗，试验组加用25％硫酸镁4ml加入5％葡萄糖液250ml中静脉滴注1小时，10％葡萄糖酸钙10ml加入10％葡萄糖液20ml中静脉注射15分钟，均于用奥沙利铂前后各8小时应用。两组中奥沙利铂均加入5％葡萄糖液250ml中静脉滴注2-3h。两组病例均于第1疗程前及4疗程后检测神经传导速度，并于4疗程后按奥沙利铂特定感觉神经毒性分级标准评定。结果发现：4周期治疗结束后，在A组可评价的24例病例中发生1级神经毒性4例，2、3级均0例，总发生率16.6％。在B组可评价的23例病例中发生1级神经毒性9例，2级2例，3级1例，总发生率52.1％两组有显著性差异(P＜0.05)。神经传导速度检测提示有神经毒性的患者出现明显的神经电生理学的异常。因此我们得出结论：硫酸镁联合葡萄糖酸钙能降低奥沙利铂神经毒性的发生率，值得进一步研究，以更好地预防奥沙利铂神经毒性的发生。更多还原

【Abstract】 Oxaliplatin is the third-generation platinum. Several Studies show that Oxaliplatin has inhibitory effect on some tumour cell lines in vivo and vitro, including in which resistant to cisplatin or carboplatin. Oxaliplatin is active in colorectal cancer, gastric cancer, lung cancer et al. Neurotoxicity is its dose-limiting toxicity, which may comes from an effect on neuronal voltage-gated Na channels through the liberation its metabolite, oxalate. We decided to use Ca⁺⁺ and Mg⁺⁺ as oxalate chelators to prevent the neurotoxicity caused by Oxaliplatin.In this study, 47 patients treated with oxaliplatin-based regimen were randomized to two groups. 24 patients in A group （test group） received chemotherapy combination with magnesium sulfate and calcium gluconate. 23 patients in B group （control group） received chemotherapy alone. A group received infusions of Ca gluconate （10% Ca gluconate 10ml add in 10% dextrose 20ml, infusion for 15mins） and Mg sulfate （25 % Mg sulfate 4ml add in 5 % dextrose 250ml, infusion for 1hr） 8 hour before and after infusion of oxaliplatin . Oxaliplatin add in 5% dextrose were given within 2-3hr infusion. Nerve conduction velocity was performed at baseline and after four cycles of chemotherapy in all patients. Aspecific neurotoxicity scale was used for oxaliplatin-related neurotoxicity after four cycles of chemotherapy.Result: After four cycles, only 4 of 24 assessable patients in the group A suffered from Grade 1 neurotoxicity. 12 of 23 assessable patients in the group B suffered from neurotoxicity, including 9 cases for Grade 1,2 cases for Grade 2 ,1 case for Grade 3 neurotoxicity. The incidence rate of neurotoxicity in group A was 16.6% and that in group B was 52.1% , there were significant deviation between two groups（P<0.05） . The nerve conduction velocity showed abnormal change of neurophysiology in patients who suffered from neurotoxicity.Conclusions: Magnesium Sulfate and Calcium Gluconate infusion can reduce the incidence of Oxaliplatin-Related Neurotoxicity.更多还原