Ca/Mg infusions for the prevention of oxaliplatin-related neurotoxicity in patients with colorectal cancer: a meta-analysis

Abstract

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.