Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Ann Oncol. 2013 Jan;24(1):171-8. doi: 10.1093/annonc/mds211. Epub 2012 Aug 16.
Oxaliplatin-related neurotoxicity is the main limitation for its continuation in adjuvant and palliative chemotherapy for patients with colorectal cancer. The purpose of this meta-analysis was to determine the efficacy of calcium and magnesium (Ca/Mg) infusions in oxaliplatin-induced neurotoxicity.
Two independent authors conducted database searches of the literature to find clinical-controlled trials analyzing Ca/Mg infusions in oxaliplatin-induced neurotoxicity. The keywords used to search were oxaliplatin, neurotoxicity, calcium, magnesium, neuropathy, and peripheral. Clinical studies that included at least one primary or secondary event were eligible for the analysis, where primary events were incidences of acute and cumulative neurotoxicity, and secondary events were the total doses and cycles of oxaliplatin, response rate (RR), overall survival (OS), and progression-free survival (PFS). Odds ratios (ORs) and weighted mean differences (MD) were analyzed using models of fixed and random effects.
This meta-analysis comprised four prospective randomized clinical trials and three retrospective clinical trials involving 1170 colorectal cancer patients, of which 802 received Ca/Mg infusions (Ca/Mg group) and 368 did not (control group). According to the National Cancer Institute-Common Terminology Criteria for Adverse Events, the incidence of grade 3 acute neurotoxicity in those who received Ca/Mg was significantly lower than that of the control group (OR=0.26; 95% confidence interval (CI), 0.11 to 0.62; P=0.0002). The total rate of cumulative neurotoxicity, and that of grade 3 in particular, was significantly lower in the Ca/Mg group than in the control group (OR=0.42; 95% CI 0.26-0.65; P=0.0001; OR=0.60; 95% CI 0.39-0.92; P=0.02, respectively). The differences in total doses and cycles of oxaliplatin were also significant between the Ca/Mg and control group (MD=246.73 mg/m2; 95% CI 3.01-490.45; P=0.05; MD=1.55; 95% CI 0.46-2.63; P=0.005, respectively). No significant differences were found in median PFS (MD=0.71 month; 95% CI -0.59-2.01; P=0.29), median OS (MD=0.10 month; 95% CI -0.41-0.61; P=0.70) or RRs (OR=0.82; 95% CI 0.61-1.10; P=0.18).
Ca/Mg infusions tend to decrease the incidence of oxaliplatin-induced acute and cumulative neurotoxicity and thus enhance patients' tolerance to oxaliplatin, without significantly altering the efficacy of chemotherapy.
奥沙利铂相关的神经毒性是其在结直肠癌辅助和姑息化疗中继续使用的主要限制。本荟萃分析的目的是确定钙镁（Ca/Mg）输注在奥沙利铂诱导的神经毒性中的疗效。
两位独立的作者对文献进行了数据库检索，以寻找分析 Ca/Mg 输注在奥沙利铂诱导的神经毒性中的临床对照试验。用于搜索的关键字包括奥沙利铂、神经毒性、钙、镁、神经病和外周。符合分析条件的临床研究至少包括一个主要或次要事件，其中主要事件是急性和累积神经毒性的发生率，次要事件是奥沙利铂的总剂量和周期、反应率（RR）、总生存期（OS）和无进展生存期（PFS）。使用固定效应和随机效应模型分析比值比（OR）和加权均数差值（MD）。
本荟萃分析包括四项前瞻性随机临床试验和三项回顾性临床试验，共涉及 1170 例结直肠癌患者，其中 802 例接受了 Ca/Mg 输注（Ca/Mg 组），368 例未接受（对照组）。根据国家癌症研究所常见不良事件术语标准，接受 Ca/Mg 治疗的患者 3 级急性神经毒性的发生率明显低于对照组（OR=0.26；95%置信区间（CI）0.11-0.62；P=0.0002）。Ca/Mg 组累积神经毒性的总发生率，特别是 3 级累积神经毒性的发生率，明显低于对照组（OR=0.42；95%CI 0.26-0.65；P=0.0001；OR=0.60；95%CI 0.39-0.92；P=0.02）。Ca/Mg 组和对照组之间奥沙利铂的总剂量和周期也存在显著差异（MD=246.73mg/m2；95%CI 3.01-490.45；P=0.05；MD=1.55；95%CI 0.46-2.63；P=0.005）。中位无进展生存期（MD=0.71 个月；95%CI -0.59-2.01；P=0.29）、中位总生存期（MD=0.10 个月；95%CI -0.41-0.61；P=0.70）或 RR（OR=0.82；95%CI 0.61-1.10；P=0.18）无显著差异。
Ca/Mg 输注可降低奥沙利铂诱导的急性和累积神经毒性的发生率，从而提高患者对奥沙利铂的耐受性，而不显著改变化疗的疗效。
