The Use of Calcium and Magnesium to Prevent Neurotoxicity in Patients Receiving Oxaliplatin

Authors' disclosures of potential conflicts of interest are found at the end of this article. A groundbreaking oral abstract was presented by Charles Loprinzi at the 2013 annual meeting of the American Society of Clinical Oncology (ASCO), addressing the controversial issue of using magnesium and calcium to prevent oxaliplatin-induced sensory neuropathy. Results of the study were subsequently published in the Journal of Clinical Oncology [Lo-prinzi et al., 2014]). This practice has varied among many institutions for nearly a decade due to the lack of a clear message in the literature to support or contest this practice. The phase III randomized, placebo-controlled, double-blinded study was conducted by Loprinzi et al. with the primary objective of determining whether the use of 1 g of calcium gluconate and 1 g of magnesium sulfate reduced cumulative sensory neuropathy. The trial included 353 total patients being treated with adjuvant 5-fluorouracil, oxaliplatin, and leucovorin (FOLFOX) for colon cancer. Patients were divided among three arms. The first arm included 118 patients who received calcium and magnesium before and after oxalipla-tin. The second arm included 116 patients who received calcium and magnesium before oxaliplatin, followed by placebo. The third arm included 119 patients who received placebo before and after oxaliplatin. The primary endpoint used the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-CIPN20 scale to measure sensory neuropathy. The Common Terminology Criteria for Adverse Events (CTCAE) 4.0 and an oxaliplatin-specific neurotoxicity scale were used to measure secondary endpoints of median days to grade 2 sensory neurotoxicity. Acute sensory neu-ropathy was also assessed for 5 days after oxaliplatin. The study concluded that the use of Ca/Mg to prevent sensory neu-ropathy did not provide benefit to patients from an acute or cumulative neuropathy standpoint. There was no difference found among all arms when using the oxaliplatin-specific neuropathy scale, the CTCAE scale, or the QLQ-CIPN20 scale with respect to median days to development of grade 2 sensory neuropathy (Lo-prinzi et al., 2014).