钙镁预防奥沙利铂急性神经毒性的临床研究

 目的 评价钙、镁注射液对奥沙利铂急性神经毒性的预防作用。方法　将42例晚期大肠癌患者随机分为化疗+钙、镁组（研究组）和单纯化疗组（对照组），每组各21例。两组患者采用的化疗方案基本相同，均以奥沙利铂为基础，对照组用奥沙利铂130 mg／m2加入5 %葡萄糖液500 ml中静脉滴注3 h，第1天；雷替曲塞3 mg／m2，静脉推注15 min，第1天或四氢叶酸钙（CF）200 mg／m2，静脉滴注，第1天至第5天，5-氟尿嘧啶（5-Fu）500 mg／m2，静脉滴注，第1天至第5天，每3周为1个周期，共2 ~ 6个周期。研究组在奥沙利铂滴注前后，加用10 %葡萄糖酸钙和25 %硫酸镁各1 g，静脉推注15 min以上。神经毒性采用奥沙利铂特定的分级标准进行评价。结果　研究组和对照组的急性神经毒性的发生率分别为47.62 %和90.48 %，差异具有统计学意义（χ2＝9.02，P < 0.005），其中研究组Ⅲ度神经毒性的发生率为4.76 %，显著低于对照组的33.33 %（χ2 = 5.56，P < 0.05）。另外钙、镁注射液未显示有明显的毒副作用，研究组和对照组的客观有效率（OR）分别为33.33 %和28.57 %，差异无统计学意义（P > 0.05）。结论　钙、镁可有效预防奥沙利铂的急性神经毒性，且不影响奥沙利铂的疗效，但钙、镁的药物剂量和实施方法有待进一步探讨。

Clinical study of prevention of oxaliplatin-induced acute neurotoxicity by calcium and magnesium infusions

Objective To evaluate the efficacy of calcium(Ca) and magnesium (Mg) infusions in pre－vention of oxaliplatin-induced acute neurotoxicity. Methods Fourty-two patients with advanced colorectal carcinoma were eligible for the study: 21 were assigned to the Ca/Mg arm and 21 to the control arm . The Ca/Mg arm and the control arm were comparable for patients' characteristics. Chemotherapy regimen were al－most the same in both arms. Chemotherapy regimen consisted of oxaliplatin 130 mg/m2 on day 1, given as a 3-hour infusion in 500 ml of 5 % glucose, concurrent with raltitrexed 3 mg/m2 as a 15-minute intravenous (IV) infusion or calcium folinate (CF) 200 mg·m-2·d-1, days 1~5, 5-Fluorouracil (5-Fu) 500 mg·m-2·d-1, days 1~5. Therapy was repeated every 3 weeks. The treatment consisted of Ca gluconate and Mg sulfate, 1 g each, delivered i.v. over 15 min just before the oxaliplatin infusion and repeated at the same dose after the comple－tion of the oxaliplatin infusion. A specific neurotoxicity scale was used for oxaliplatin-related neurotoxicity. Results Ten patients (47.62 %) had acute neurotoxicity in the Ca/Mg arm compared with 19 patients (90.48 %) in the control arm (P < 0.005). Remarkably, the incidence of grade 3 acute neurotoxicity was 4.76 % in the Ca/Mg arm, which was significantly lower than 33.33 % in the control arm (P < 0.05). No Ca/Mg-induced toxicity has been reported in patients of Ca/Mg arm. The overall response rate was 33.33 % in the Ca/Mg arm compared with 28.57 % in the control arm (P > 0.05). Conclusion Ca/Mg infusions seem to reduce incidence and intensity of oxaliplatin-induced acute neurotoxicity, and they do not reduce the clinical activity of oxaliplatin, but dosage and administration schedule could be optimized.