Knijn N., Tol, J., Koopman, M., Werter M.J., Imholz, A.L., Valster, F.A., . . . Punt C.J. (2011). The effect of prophylactic calcium and magnesium infusions on the incidence of neurotoxicity and clinical outcome of oxaliplatin-based systemic treatment in advanced colorectal cancer patients. European Journal of Cancer, 47, 369–374.

The purpose was to assess the effect of calcium and magnesium infusions on incidence of neurotoxicity and clinical outcomes in patients treated in a phase III trial (CAIRO2) with oxaliplatin-based chemotherapy.

Patients who had been treated in an randomized clinical trial for advanced colorectal cancer with either capecitabine, oxaliplatin, and bevacizumab or the same regimen with the addition of cetuximab were retrospectively divided into two groups: those who had received calcium and magnesium infusion at least during the first oxaliplatin cycle and those who did not receive calcium and magnesium during cycle 1. To evaluate the impact on prevention, incidence of neurotoxicity was defined as early (occurring during the first six cycles) or late (present at the last cycle).

• A total sample of 732 participants with colon cancer were enrolled, with men (60%) outnumbering women (40%).
• The mean age of participants was 61.9 years with a range of 27–83 years.

The study was conducted in multiple outpatient facilities in Norway.

• Active treatment
• Late effects

The study was a retrospective analysis of trial data.

• The National Cancer Institute's Common Terminology Criteria for Adverse Events, version 3.0.
• An evaluation of tumor response with the Response Evaluation Criteria in Solid Tumors (RECIST).

Sample sizes were varied between groups, with 551 having received calcium and magnesium and 181 who did not. Incidence of any grade neurotoxicity was 85% in those who received calcium and magnesium and 92% in those who did not (p = 0.02), and incidence of grade 2 or higher was not significantly different between groups. Early neurotoxicity of any grade occurred more often in those who did not receive calcium and magnesium (91% versus 81%, p = 0.0002). In addition, no significant difference were noted between groups in incidence of grade 2 or higher early toxicity. All grade late neurotoxicity was lower in those who were in the calcium and magnesium group; however, incidence of grade 2or higher late toxicity was no different between groups. No difference was noted in survival or response rates between study groups.

Findings suggest that calcium and magnesium infusion may be helpful in the prevention of neurotoxicity with oxaliplatin; however, findings do not show a clear difference in more severe toxicity of grade 2 or higher.

• Limitations include the retrospective nature of the study with no appropriate control in place.
• The authors define the calcium and magnesium group as getting this infusion with the first cycle of chemotherapy; however, whether or not any of these patients or other patients got any such infusions with later cycles is unclear.
• The only outcome measure is the toxicity grading scale.
• No information is provided regarding total cumulative chemotherapy doses (whether any cycles were not provided, etc.) to evaluate any differences in symptoms according to chemotherapy dosage and cycle completions.

The findings suggest the potential effect of calcium and magnesium infusions in the prevention of neurotoxicity; however, the findings do not show any difference in terms of prevalence of higher grade neurotoxicity. Additional research in this area is needed with more definitive outcome measures.