which gonadotoxic chemotherapies are the most common in children?

Common Gonadotoxic Chemotherapies Used in Children:

In pediatric oncology, alkylating agents are among the most commonly used chemotherapies known for their gonadotoxic potential. Specifically, ifosfamide is a frequently used alkylating agent in children treating cancers such as Ewing's sarcoma, rhabdomyosarcoma, osteosarcoma, and various lymphomas SmPC Ifosfamide,SmPC Ifosfamide,Hafele et al. 2025. Ifosfamide is associated with a risk of infertility in both sexes via interference with oogenesis and spermatogenesis, potentially causing sterility dose-dependently, with risks of amenorrhea, oligospermia, or azoospermia SmPC Ifosfamide,SmPC Ifosfamide.

Other alkylating agents, including cyclophosphamide and busulfan, are also widely used in pediatric cancers like leukemia and lymphoma and carry significant gonadotoxic risks, contributing to premature ovarian insufficiency (POI) and testicular dysfunction Hafele et al. 2025,PubMed,Foster et al. 2024. The cumulative exposure to alkylating agents can be quantified by the cyclophosphamide equivalent dose (CED), with CEDs exceeding 4 g/m2 associated with higher infertility risks in children PubMed.

Additionally, platinum-based compounds such as cisplatin are commonly administered in pediatric solid tumors and are recognized for their moderate to high gonadotoxic potential impacting fertility in both boys and girls Hafele et al. 2025,Foster et al. 2024.

Other chemotherapies less gonadotoxic include vinca alkaloids like vincristine, which is often part of combination regimens in childhood cancer but has a comparatively lower risk of gonadal damage Reynolds and McKenzie LJ. 2023,Foster et al. 2024.

Overall, the most common gonadotoxic chemotherapies in children are alkylating agents including ifosfamide and cyclophosphamide, busulfan, and platinum compounds such as cisplatin, which together contribute significantly to the risk of impaired fertility in childhood cancer survivors SmPC Ifosfamide,SmPC Ifosfamide,PubMed,Hafele et al. 2025,Foster et al. 2024.

Contextual Notes:

• These agents are incorporated into treatment protocols for a range of pediatric cancers, including leukemias, lymphomas, sarcomas (including Ewing’s and rhabdomyosarcoma), neuroblastoma, Wilms’ tumor, and CNS tumors SmPC Ifosfamide,SmPC Ifosfamide,NICE CKS,Hafele et al. 2025.
• Fertility preservation approaches, including sperm cryopreservation and testicular or ovarian tissue cryopreservation, are increasingly considered prior to initiation of these therapies, given the substantial gonadotoxicity of these chemotherapy classes NICE CG156,PubMed,Hafele et al. 2025.
• Standard protocols emphasize informing families and patients at diagnosis about the potential fertility risks of these chemotherapies and integrating fertility preservation advice into the treatment pathway NICE CG156,PubMed.