氨磷汀预防消化道肿瘤草酸铂化疗引起的神经毒性

Prophylactic Effect of Amifostine on Oxaliplatin-related Neurotoxicity in Patients with Digestive Tract Tumors

背景与目的:草酸铂广泛用于消化道肿瘤的化疗,突出的神经毒性限制了剂量和疗效的提高。本研究旨在评价氨磷汀对草酸铂神经毒性的防治效果。方法:92例FOLFOX4方案化疗的结直肠癌、胃癌患者,随机进入氨磷汀组(草酸铂前静脉注射氨磷汀500mg/m2,n=46)或对照组(草酸铂前静脉注射还原性谷胱甘肽1500mg/m2,n=46)。每化疗2周期详细评价神经毒性。结果:氨磷汀组Ⅰ～Ⅱ度和Ⅲ～Ⅳ度神经毒性发生率与对照组相比,分别为10.9%:73.9%(P<0.001)和2.2%:19.6%(P=0.007),均显著降低。氨汀组因化疗毒性的方案改变明显少于对照组(4.3%:23.9%,P=0.007)。化疗近期有效率氨磷汀组与对照组差异无显著性(44.4%:38.5%,P=0.659)。结论:氨磷汀对含草酸铂方案化疗的神经毒性有明显防治作用,不降低化疗疗效。

BACKGROUND ＆ OBJECTIVE. Oxaliplatin, an active agent used widely in treating digestive tract tumors, displays a frequent doselimiting neurotoxicity. This study was to assess the clinical efficacy of amifostine in preventing neurotoxicity induced by oxaliplatin. METHODS= A total of 92 patients with colorectal cancer or gastric cancer were enrolled, and randomly assigned to receive amifostine （500 mg/m^2） （amifostine group, 46 patients） or glutamine （1500 mg/m^2） （control group, 46 patients） just before oxaliplatin infusion. All patients received FOLFOX4 regimen. Neurological toxicity and efficacy of chemotherapy were assessed. RESULTS The occurrence rates of grade I - II and grade III-IV peripheral neurotoxicity after chemotherapy were significantly lower in amifostine group than in control group （10.9% vs. 73.9%, P〈0.001; 2.2% vs. 19.6%, P= 0.007）. The frequency of regimen change because of chemotherapy-related neurotoxicity was significantly lower in amifostine group than in control group （4.3% vs. 23.9%,P=0.007）. The overall response rates of evaluable patients were 44.4% in amifostine group and 38.5% in control group （P=0.66）. CONCLUSION= Amifostine could significantly reduce the occurrence and severity of peripheral neurotoxicity caused by oxaliplatin in the patients with digestive tract tumors, but not affect response to chemotherapy.