Evaluation of intravenous preloading magnesium supplementation as a preventive measure of cisplatin induced nephrotoxicity

Abstract

Nephrotoxicity remains a problem for patients who receive cisplatin based chemotherapy. Magnesium depletion is known as a complication to chemotherapy with cisplatin and likely to enhance nephrotoxicity. The National Comprehensive Cancer Networkrecommended 8mEq intravenous magnesium supplementation as a preventive measure of cisplatin-induced nephrotoxicity. This intervention is not yet applied in our setting due to lack of strong evidence. OBJECTIVE: To evaluate the effect of intravenous magnesium preloading supplementation on cisplatin-induced nephrotoxicity in cancer patients on cisplatin combination chemotherapy at Kenyatta National Hospital and Texas Cancer Centre, Kenya. STUDY METHODOLOGY: 71 patients diagnosed with cancer and who were to receive their first cycle of cisplatin-based chemotherapy at Kenyatta National Hospital or Texas Cancer Center at a single dose 60 mg/m2 or above of cisplatin on day 1 were randomly assigned to receive intravenous magnesium preloading supplementation or not as part of their chemotherapy regimen. Serum creatinine was measured, and creatinine clearance (CrCl) was estimated by the Cockcroft–Gault equation. The follow-up period was 17 days. The primary outcome measure was incidence of acute kidney injury grade 1 or higher as defined by Common Terminology Criteria for Adverse Event 4.03. Kaplan-Meier survival analysis and Cox regression analysis were also performed to enable comparison of nephrotoxicity-free survival times and identify predictor factors for cisplatin-induced nephrotoxicity. RESULTS: There was a significant decrease in the incidence of CIN in the Magnesium Preloading Group, compared to the Non-Magnesium Preloading group (12.12 % vs 33.13%, respectively; P = 0.037). Intravenous Magnesium sulfate supplementation also reduced the severity of CIN as it significantly reduced the mean maximum change in serum creatinine (0.10 mg/dL (range: -0.090, 1.761) versus 0.19 mg/dL (range: -0.147, 1.86); P = 0.006) and the mean maximum change in creatinine clearance (-13.2 ml/min (range: -56.3, 17.9) versus -22.05 ml/min (range: -112.8, 16.5); P= 0.041) in the magnesium supplementation group compared to the nonmagnesium supplementation group, respectively. Survival analysis showed that magnesium supplementation also increased the nephrotoxicity-free survival time (P=0.042). Esophageal cancer and BUN>5 mmol/l were identified as significant predictive factors for cisplatin-induced nephrotoxicity. CONCLUSION: The study has provided strong and direct evidence in support of the application of intravenous preloading magnesium supplementation at the dose of 8 mEq before administration of cisplatin as a preventive measure of cisplatin-induced nephrotoxicity in cancer patients treated with cisplatin-based regimen.