Oral Magnesium for Reduce Febrile Neutropenia in Children with Solid Tumors Treated with Cisplatin-Based Chemotherapy: Randomized Clinical Trial

Abstract

Background: Hypomagnesemia has been associated with febrile neutropenia (FN) in pediatric patients receiving cisplatin-based chemotherapy (CDDPBC). The primary aim was to determine whether oral magnesium supplementation reduces FN episodes in pediatric patients with solid tumors treated with CDDPBC. Methods: This randomized clinical trial, open label, single center, parallel groups and superiority design was conducted in Hospital Infantil de Mexico Federico Gomez at Mexico City. Children ≥ 9 years with solid tumors that were to receive a CDDPBC cycle were invited to participate. Each cycle of chemotherapy with CDDPBC were randomly assigned to receive oral magnesium supplementation (250 mg per day) or not receive magnesium supplementation (control group). Efficacy was determined by relative risks (RR) with 95% confidence intervals (95%CI) as well as with numbers needed to treat (NNT). Active surveillance was conducted to assess safety in both groups. Analyzes were made by intention to treat. This study is registered with ClinicalTrials.gov, number NCT03449693. Findings: between October 2017 and February 2019, eighty-two cycles of chemotherapy with CDDP were analyzed (42 in the magnesium supplement arm and 40 in control group). Baseline clinical characteristics were similar comparing both groups. Oral magnesium supplementation reduces FN episodes compared to control group (RR= 0.48, [95%CI, 0.26 to 0.89], NNT= 4). In the group supplemented with magnesium presented lower risk of septic shock secondary to FN (RR= 0.29, [95%CI, 0.09 to 0.96], NNT= 6). Adverse evets were similar across both groups. Interpretation: Oral supplementation with magnesium reduces episodes of febrile neutropenia in pediatric patients with solid tumors treated with CDDPBC. Trial Registration Number: This study is registered with ClinicalTrials.gov, number NCT03449693. Funding: This work was supported by Direccion General de Asuntos del Personal Academico, Universidad Nacional Autonoma de Mexico (DGAPA, UNAM), PAPIIT Grant IA207417. Declaration of Interest: Nothing to declare. Ethical Approval: The study was approved by HIMFG Institutional Review Board (HIM 2017-85) and registered prospectively in Clinical Trial Registry (NCT03449693).