Xu, X.T., Dai, Z.H., Xu, Q., Qiao, Y.Q., Gu, Y., Nie, F., . . . Ran, Z.H. (2013). Safety and efficacy of calcium and magnesium infusions in the chemoprevention of oxaliplatin-induced sensory neuropathy in gastrointestinal cancers. Journal of Digestive Diseases, 14, 288–298.

STUDY PURPOSE: To identify all observational studies that examine the role of calcium and magnesium infusions in the chemoprevention of oxaliplatin-induced sensory neuropathy in gastrointestinal cancers

DATABASES USED: PubMed, EMBASE, Science Citation Index, Expanded Chinese National Knowledge Infrastructure

KEYWORDS: Calcium gluconate; digestive system neoplasms; magnesium sulfate; neurotoxicity syndrome; oxaliplatin; oxaliplatine; eloxatine; ACT 078 L-HP; neuropathy; chemotherapeutic agent; toxicity; calcium; Ca; Ca and magnesium; Mg or Mg and oesophageal cancer; gastric cancer; stomach cancer; bowel cancer; colorectal cancer; colon cancer; rectal cancer; pancreatic cancer; hepatocellular carcinoma; liver cancer; biliary tract cancer

INCLUSION CRITERIA: Studies for meta-analysis included randomized, controlled trials and cohort studies that involved calcium and magnesium infusions in chemoprevention of oxaliplatin-induced sensory neurotoxicity in gastrointestinal cancers.

EXCLUSION CRITERIA: Letters, case studies, reviews, comments, studies on cell lines, animal studies, and any study with no control group

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: National Cancer Institute Common Toxicity Criteria (NCI CTC) and oxaliplatin-specific scale (OSS) were used. Meta-analysis was done on six studies that had reported responses. A sensitivity analysis was used by repeating meta-analysis but excluding one study at a time. Odds ratio and its 95% confidence interval were calculated.

• FINAL NUMBER STUDIES INCLUDED = 16 (15 full manuscripts and one abstract)
• TOTAL PATIENTS INCLUDED IN REVIEW: 1,765
• KEY SAMPLE CHARACTERISTICS: The studies were randomized, controlled trials, prospective and retrospective, that included magnesium and calcium infusions for the prevention of chemotherapy-induced neuropathy in patients with gastrointestinal cancers. Patients had gastrointestinal, colorectal, hepatocellular, and small intestine cancers. Patients were aged 18–37 years.

• PHASE OF CARE: Survivorship
• APPLICATIONS: Pediatrics, elder care

The difference in the incidence of grade 1 oxaliplatin-induced neuropathy was statistically significant between those who received calcium and magnesium infusions and those who did not receive the treatment (NCI CTC: OR .44, 95% CI 0.31–0.62, p = 0.000; OSS: OR 0.30, 95% CI 0.20–0.45, p = 0.000). Similar results were found in the incidence of grade 2 oxaliplatin-induced neuropathy (NCI CTC: OR 0.60, 95% CI 0.46–0.77, p = 0.000; OSS: OR .45, 95% CI 0.30–0.67, p = 0.000). No difference was observed in grade 3 neuropathy in patients treated with calcium and magnesium infusions opposed to those who were not treated with calcium and magnesium infusions (NCI CTC: OR 0.67, 95% CI 0.44–1.01, p = 0.054; OSS: OR 0.66, 95% CI 0.34–1.29, p = 0.224). Overall, calcium and magnesium infusions reduced the incidence of peripheral neuropathy grades 1 and 2. This did not include the incidence of grade 3 neuropathy. The calcium and magnesium infusions did not lessen the treatment effects of oxaliplatin (OR 0.89, 95% CI 0.67–1.17, p = 0.391).

Most research in chemotherapy-induced peripheral neuropathy has focused on treatment-related side effects. Positive studies in this area are lacking. However, this analysis of six studies of calcium and magnesium infusions in the prevention of chemotherapy-induced peripheral neuropathy is promising. Large, randomized trials would need to be done to determine efficacy.

• More than likely, studies that had negative results were not published, so the authors concluded that bias could not be ruled out.
• The design of the studies varied greatly. The majority of the studies were retrospective or nonblinded observations.
• There may be a discrepancy in the results because the number of treatments, duration of treatments, cumulative doses of oxaliplatin, assessment scales, and timing of assessments varied.
• Given the small subgroup and that the analysis did not provide all of the information needed, care should be taken in interpreting the results and conclusions.

One of the limitations speaks to lack of consistency among various assessment scales for peripheral neuropathy. Whether a preventive study or treatment study, assessment is critical to patients with peripheral neuropathy. Nurses should be knowledgeable concerning various assessment scales and should use the scales from baseline through survivorship.