Loprinzi, C.L., Qin, R., Dakhil, S.R., Fehrenbacher, L., Flynn, K.A., Atherton, P., . . . Grothey, A. (2014). Phase III randomized, placebo-controlled, double-blind study of intravenous calcium and magnesium to prevent oxaliplatin-induced sensory neurotoxicity (N08CB/Alliance). Journal of Clinical Oncology, 32, 997–1005.

To provide a definitive test of the effectiveness of calcium and magnesium in decreasing oxaliplatin-induced neurotoxicity

Patients randomly were assigned to receive intravenous calcium gluconate and magnesium sulfate at 1 g each in 100 ml of D5W over the course of 30 minutes immediately prior to and after each dose of oxaliplatin. Patients in the control group received a placebo that appeared identical to the study drug with the same administration timing. A third group was administered calcium and magnesium before chemotherapy and a placebo after infusion. Patients with adenocarcinoma of the colon scheduled to receive 12 cycles of FOLFOX chemotherapy including 85 mg/m² oxaliplatin every two weeks were considered for participation. Oxaliplatin dose modifications were not prescribed by the study, but dosage changes or delays were provided as recommendations. Study measures were obtained at each cycle of chemotherapy.

• N = 326 
• MEDIAN AGE = 56 years
• MALES: 48%, FEMALES: 52%
• KEY DISEASE CHARACTERISTICS: All participants were patients with colon cancer receiving either FOLFOX-4 or mFOLFOX-6 treatment.
• OTHER KEY SAMPLE CHARACTERISTICS: 85% Caucasian; majority were diagnosed with stage II disease

• SITE: Multi-site  
• SETTING TYPE: Multiple settings    
• LOCATION: More than 50 sites in the United States

• PHASE OF CARE: Active antitumor treatment

Three-group, double-blinded, placebo-controlled, randomized trial

• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ) for Chemotherapy-Induced Peripheral Neuropathy (CIPN20)
• National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE)

There were no significant differences between the three study arms on the EORTC-QLQ CIPN20 sensory or motor neuropathy scales. There were no significant differences in neurotoxicity assessment using the CTCAE to determine time till grade 2 neurotoxicity or incidence of grade 2 symptoms. A subgroup analysis did not show evidence of benefit in groups according to age, sex, disease stage, or specific FOLFOX regimen. There were no differences in acute or chronic symptoms.

The findings of this study do not support the use of intravenous calcium gluconate and magnesium sulfate to prevent oxaliplatin-induced neuropathy.

This large, well designed trial showed no benefit of the use of a calcium gluconate and magnesium sulfate infusions to prevent peripheral neuropathy in patients receiving FOLFOX. The authors of this study state that as many as 50% of practitioners continue to use this intervention, and resources such as UpToDate suggest consideration of this intervention. Nurses can advocate that calcium gluconate and magnesium sulfate not be used for the prevention of peripheral neuropathy given the lack of evidence for its efficacy. This can save time and expense in treatment for patients receiving this type of chemotherapy. Additional similar research may be needed to examine this treatment's effects in patients at risk for peripheral neuropathy related to other chemotherapeutic agents.