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. 2025 Sep;174(3):689-697.
doi: 10.1007/s11060-025-05098-7. Epub 2025 Jun 10.

Impact of partial substitution of cisplatin with cyclophosphamide on acute toxicities in standard-risk medulloblastoma

Sarah Magdy Metwally #  1   2 , Moatasem El-Ayadi #  3 , Eslam Maher  4   5 , Mohamed Sherif El-Minawi  6   7 , Mohamed S Zaghloul  8   9 , Hala Taha  10   11 , Sherif Aboulnaga  3   12 , Iman Sidhom  13   14
Affiliations

Impact of partial substitution of cisplatin with cyclophosphamide on acute toxicities in standard-risk medulloblastoma

Sarah Magdy Metwally et al. J Neurooncol. 2025 Sep.

Abstract

Purpose: Medulloblastoma (MB) treatment includes surgery, irradiation, and chemotherapy (CT). Cisplatin-based regimens for standard-risk (SR) MB are effective but associated with significant toxicities, particularly ototoxicity. This study compares the toxicity profiles of two CT regimens, focusing on grade ≥ 3 ototoxicity, hematologic, hepatic, renal, and neurologic toxicities.

Methods: This study included SR-MB patients aged 3-18 years. Cohort A (2016-2019) received adjuvant CT adopted from the Children's Oncology Group (COG) A9961 Regimen A protocol, with data collected retrospectively. Cohort B (2020-July 2022) received CT adopted from the ACNS0331 protocol, with data collected prospectively. Toxicities were assessed and graded using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Results: A total of 168 patients aged 3 to 18 years were enrolled, 112 (67%) in cohort A and 56 (33%) in cohort B. Grade ≥ 3 ototoxicity was significantly higher in cohort A (24% vs. 3.6%, p < 0.001). Neurotoxicity occurred in 26% vs. 12.5% (p = 0.046). Anemia and thrombocytopenia in 71% vs. 52% (p = 0.04). Febrile neutropenia was more common in cohort B (66% vs. 38%, p < 0.001). No significant differences were found in grade ≥ 3 leukopenia, nephrotoxicity or hepatotoxicity. The 2-year overall survival was 96.4% (95% CI: 93.1-99.9) in cohort A vs. 86.6% (95% CI: 77.8-96.4) in cohort B (p = 0.11). Event-free survival was 92.9% (95% CI: 88.2-97.8) vs. 86.8% (95% CI: 78-96.4) (p = 0.29).

Conclusion: Partial substitution of cisplatin with cyclophosphamide showed a better toxicity profile, particularly for ototoxicity and neurotoxicity, with no significant difference in survival.

Keywords: Chemotherapy; Cisplatin; Cyclophosphamide; Medulloblastoma; Ototoxicity; Toxicity.

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Conflict of interest statement

Declarations. Ethical approval: The study was approved by the Institutional Review Board (IRB) at CCHE (IRB number: 52/2020). No additional consent was required, as patients had already signed institutional chemotherapy-specific consent. Privacy and confidentiality of patients’ data were ensured. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Comparison of grade ≥ 3 toxicities between both cohorts
Fig. 2
Fig. 2
a Overall Survival for Both Regimens. b Event-Free Survival for Both Regimens
See this image and copyright information in PMC

References

    1. Fang FY, Rosenblum JS, Ho WS, Heiss JD (2022) New developments in the pathogenesis, therapeutic targeting, and treatment of pediatric Medulloblastoma. Cancers (Basel) 14(9):2285. 10.3390/cancers14092285 - DOI - PMC - PubMed
    1. Orr BA (2020) Pathology, diagnostics, and classification of Medulloblastoma. Brain Pathol 30(3):664–678. 10.1111/bpa.12837 - DOI - PMC - PubMed
    1. Choi JY, Medulloblastoma (2023) Current perspectives and recent advances. Brain Tumor Res Treat 11(1):28. 10.14791/btrt.2022.0046 - DOI - PMC - PubMed
    1. Michalski JM et al (2021) Children’s oncology group phase III trial of Reduced-Dose and Reduced-Volume radiotherapy with chemotherapy for newly diagnosed Average-Risk Medulloblastoma. J Clin Oncol 39(24):2685. 10.1200/JCO.20.02730 - DOI - PMC - PubMed
    1. Bailey S et al (2025) Medulloblastoma therapy: consensus treatment recommendations from SIOP-Europe and the European research network. EJC Paediatr Oncol 5:100205. 10.1016/j.ejcped.2024.100205 - DOI

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