Magnesium supplementation therapy to prevent cisplatin-induced acute nephrotoxicity in pediatric cancer: a randomized phase-2 trial.

BACKGROUND: The present study aimed to examine the effect of magnesium (Mg) supplementation on cisplatin-induced nephrotoxicity (CIN) in pediatric cancer patients. METHODS: The present phase-2, open-label, multicenter, randomized controlled trial enrolled patients aged less than 20 years who were scheduled to receive cisplatin-containing chemotherapy and randomly allocated them at a ratio of 1:1 to a Mg supplementation arm with even-numbered chemotherapy courses (arm AB) or another arm with odd-numbered courses (arm BA). Analysis objects were reconstructed into two groups depending on whether the chemotherapy course had Mg supplementation (group B) or not (group A). The primary outcome was the proportion of chemotherapy courses resulting in elevated serum creatinine per chemotherapy course. The secondary outcomes included efficacies evaluated using other biomarkers and the safety of the Mg supplementation. RESULTS: Twenty-eight patients were randomly allocated to either group (16 to arm AB and 12 to arm BA). The baseline characteristics of the groups were similar. There was no significant difference in the proportion of courses with increased serum creatinine between the groups (group A: 10% vs. group B: 6%; P = 0.465) nor was any significant difference observed in other biomarkers during any chemotherapy course. The Mg value during chemotherapy was significantly higher in group B than that in group A. No adverse events related to magnesium administration were observed. CONCLUSIONS: The study design, which treated a single chemotherapy course as a study object, failed to detect a statistically significant benefit of Mg supplementation for preventing CIN in pediatric cancer patients. TRIAL REGISTRATION: JRCT ( https://jrct.niph.go.jp/ ) Identifier UMIN000029215 jRCTs031180251. UMIN-CTR ( http://www.umin.ac.jp/icdr/index.html ) Identifier UMIN000029215.

Impact of super energy-dense oral nutritional supplementation (SED ONS) on glycemic variability and food intake postoperatively in gastric cancer patients.

PURPOSE: Adherence to oral nutritional supplements (ONS) to prevent weight loss after gastrectomy is problematic. The present study evaluated the impact of super energy-dense ONS (SED ONS; 4 kcal/mL) on glycemic change and energy intake after gastrectomy. METHODS: Gastrectomy patients were placed on continuous glucose monitoring for a 3-day observation period after food intake had been stabilized postoperatively. In addition, they were given 0, 200, and 400 kcal/day of SED ONS on Days 1, 2, and 3, respectively. The primary outcome was the area under the curve < glucose 70 mg/dL (AUC < 70). The secondary outcomes were other indices of glucose fluctuation and the amount of food and SED ONS intake. RESULTS: Seventeen patients were enrolled. The AUC < 70 did not differ significantly with or without SED ONS over the observation period. SED ONS did not cause postprandial hypoglycemia and prevented nocturnal hypoglycemia. The mean dietary intake did not change significantly during the observation period, and the total energy intake increased significantly according to the amount of SED ONS provided. CONCLUSION: SED ONS after gastrectomy increased the total energy intake without dietary reduction and it did not result in hypoglycemia.

Magnesium supplementation therapy to prevent cisplatin-induced acute nephrotoxicity in pediatric cancer: A protocol for a randomized phase 2 trial.

Although cisplatin is one of the most effective agents against various pediatric cancers, it is sometimes difficult to manage due to its dose-limiting nephrotoxicity. Magnesium sulfate (Mg) showed a kidney-protective effect against cisplatin-induced nephrotoxicity (CIN) by regulating renal platinum accumulation both in vitro and in vivo, and the body of clinical data demonstrating the efficacy of this drug in adult cancer patients is increasing.In this open, multicenter, phase-2, randomized trial, patients under age 18 years who are scheduled to receive cisplatin-containing chemotherapy will be enrolled and randomly allocated either to an Mg supplementation arm in even-numbered chemotherapy courses (arm AB) or to another arm in odd-numbered courses (arm BA), with a 1:1 allocation. Analysis objects will be reconstructed into two groups depending on whether the chemotherapy course has Mg supplementation (group B) or not (group A). The primary endpoint is the proportion of chemotherapy courses resulting in elevated serum creatinine equal to or greater than 50% of the prechemotherapy value. For the secondary endpoints, various parameters for measuring kidney function, such as serum cystatin-C, B2M, L-FABP, NGAL, and urinary NAG in the two groups will be compared. A sample size based on alpha = 5% and 80% power requires at least 40 samples per group (ideally, 60 samples per group).If Mg demonstrates efficacy, a phase-3 study to confirm the prophylactic effect of Mg supplementation in both acute and chronic CIN will be developed using novel and better biomarkers. TRIAL REGISTRATION: UMIN-CTR (http://www.umin.ac.jp/icdr/index.html) Identifier UMIN000029215.

Kidney-protective Effect of Magnesium Supplementation in Cisplatin-containing Chemotherapy for Pediatric Cancer: A Retrospective Study.

In total, 158 chemotherapy courses containing cisplatin for 37 pediatric cases of newly diagnosed cancer were divided into 2 groups depending on whether magnesium (Mg) supplementation was administered (Mg+: 92 courses) or not (Mg-: 66 courses). Renal impairment was defined as grade 2 or higher creatinine elevation (CE) after each chemotherapy course. The incidence of CE in the Mg+ was significantly lower than in the Mg- (9.8% vs. 22.7%; P=0.025). Multivariate analysis revealed that Mg supplementation significantly reduced the incidence of CE (odds ratio, 0.36; confidence interval, 0.13-0.99). In pediatric patients, Mg supplementation during cisplatin-containing chemotherapy was associated with less cisplatin-induced nephrotoxicity to prevent cisplatin-induced nephrotoxicity.