Objective  The study aimed to assess the effects of an intravenous calcium/magnesium (Ca/Mg) mixture for preventing oxaliplatin-induced neurotoxicity.

  Methods  We identified randomized and controlled clinical trials comparing intravenous Ca/Mg with placebos based on their ability to prevent oxaliplatin-induced neurotoxicity in cancer patients who received oxaliplatin-based therapy. Meta-analyses were performed on the homogeneous studies. Fixed or random-effect models were used to combine the data.

  Results  Based on the outcomes of 981 patients, 16 clinical trials were identified to meet the inclusion criteria. The meta-analyses showed statistically significant differences in favor of Ca/Mg for preventing oxaliplatin-induced neurotoxicity, including the incidence (P < 0.000 01) and severity (P < 0.000 1) of neurotoxicity, as compared with the placebos. According to the subgroup analyses of the Ca/Mg dosage, both calcium gluconate (1 g) and magnesium sulfate (1 g) before and after oxaliplatin infusion as well as the accumulated dose were significantly different as compared with the placebos. In our analyses, 13 out of all 16 trials involved the FOLFOX (folinic acid - fluorouracil - oxaliplatin) regimen, whereas the remaining 3 trials used other oxaliplatin-based regimens. The FOLFOX regimen and other oxaliplatin-based regimens showed statistically significant differences in favor of Ca/Mg for preventing oxaliplatin-induced neurotoxicity as compared with the placebos. When combined with glutathione, the prevention of oxaliplatin-induced neurotoxicity was more significant (P < 0.000 1).

  Conclusion   Ca/Mg infusion is useful for preventing oxaliplatin-induced neurotoxicity and should be considered an integral part of oxaliplatin-based chemotherapy regimen. Both calcium gluconate (1 g) and magnesium sulfate (1 g) before and after oxaliplatin infusion, as well as accumulated doses that exceeded the required dose, could effectively prevent oxaliplatin-induced neurotoxicity. Glutathione likewise enhanced the preventive effects of the Ca/Mg infusion.