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Purpose <p>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.</p> Methods <p>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.</p> Results <p>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%, <i>p</i> &lt; 0.001). Neurotoxicity occurred in 26% vs. 12.5% (<i>p</i> = 0.046). Anemia and thrombocytopenia in 71% vs. 52% (<i>p</i> = 0.04). Febrile neutropenia was more common in cohort B (66% vs. 38%, <i>p</i> &lt; 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 (<i>p</i> = 0.11). Event-free survival was 92.9% (95% CI: 88.2–97.8) vs. 86.8% (95% CI: 78-96.4) (<i>p</i> = 0.29).</p> Conclusion <p>Partial substitution of cisplatin with cyclophosphamide showed a better toxicity profile, particularly for ototoxicity and neurotoxicity, with no significant difference in survival.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月10日

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  • Sarah Magdy Metwally,
  • Moatasem El-Ayadi,
  • Eslam Maher,
  • Mohamed Sherif El-Minawi,
  • Mohamed S. Zaghloul,
  • Hala Taha,
  • Sherif Aboulnaga,
  • Iman Sidhom

摘要

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.