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

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Abstract

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.

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Data availability

The clinical data collected for this study are maintained by the author and may be shared upon reasonable request.

Abbreviations

Mg:

Magnesium sulfate

CIN:

Cisplatin-induced nephrotoxicity

GFR:

Glomerular filtration rate

B2M:

Beta-2 microglobulin

NAG:

N-acetyl-β-d-glucosaminidase

ITT:

Intention to treat

AKI:

Acute kidney injury

GCT:

Germ cell tumor

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Acknowledgements

We thank Mr. James Robert Valera for his assistance with editing this manuscript.

Funding

This study was supported by Tokyo Metropolitan Hospital, Children’s Cancer Association of Japan, and Jikei University School of Medicine.

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Authors and Affiliations

  1. Department of Pediatric Hematology/Oncology, Tokyo Metropolitan Children’s Medical Center, 2-8-29 Musashidai, Fuchu, Tokyo, 183-8561, Japan

    Motohiro Matsui, Atsushi Makimoto & Yuki Yuza

  2. Department of Pediatrics, Nihon University School of Medicine, Tokyo, Japan

    Motoaki Chin

  3. Department of Hematology/Oncology, Saitama Children’s Medical Center, Saitama, Japan

    Katsuyoshi Koh

  4. Clinical Research Support Center, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan

    Masako Tomotsune, Tetsuji Kaneko & Yoshihiko Morikawa

  5. Division of Molecular Epidemiology, Jikei University School of Medicine, Tokyo, Japan

    Motohiro Matsui

  6. Department of Nephrology, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan

    Riku Hamada

Authors
  1. Motohiro Matsui
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  2. Atsushi Makimoto
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  3. Motoaki Chin
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  4. Katsuyoshi Koh
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  5. Masako Tomotsune
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  6. Tetsuji Kaneko
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  7. Yoshihiko Morikawa
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  8. Riku Hamada
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  9. Yuki Yuza
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Contributions

MM: conceptualization; data curation; formal analysis; funding acquisition; investigation; methodology; project administration; resources; software; validation; visualization; and writing––original draft. MA: conceptualization; methodology; and writing, review, and editing. MC, KK, TM, MY, and HR: conceptualization and writing, review, and editing. TK: conceptualization; formal analysis; investigation; methodology; and writing, review, and editing. YY: writing, review, and editing. All the authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Motohiro Matsui.

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Competing interests

The authors state that there are no conflicts of interest in connection with this article.

Ethics approval

The Tokyo Metropolitan Institute for Geriatrics and Gerontology review board approved this study (H18-05).

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Matsui, M., Makimoto, A., Chin, M. et al. Magnesium supplementation therapy to prevent cisplatin-induced acute nephrotoxicity in pediatric cancer: a randomized phase-2 trial. Int J Clin Oncol 29, 629–637 (2024). https://doi.org/10.1007/s10147-024-02489-0

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  • DOI: https://doi.org/10.1007/s10147-024-02489-0

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