Age-Specific Gonadotoxic Alkylating-Agent Exposure in Pediatric and Reproductive-Age Females: A Claims-Based Study Using Cyclophosphamide Equivalent Dose.

Purpose: To describe age-specific patterns of gonadotoxic alkylating-agent exposure and evaluate how the cyclophosphamide equivalent dose (CED) framework captures real-world exposure relevant to fertility preservation in females aged 0-43 years. Methods: This descriptive study used a Japanese claims database. Patients were classified as pediatric (< 15 years) or reproductive-age (15-43 years). Twelve alkylating agents were evaluated, and six CED-calculable agents were converted to CED. Results: Among approximately 3.86 million females, 0.04% of the pediatric cohort and 0.16% of the reproductive-age cohort were exposed to at least one alkylating agent. Total CED identified at least intermediate-risk exposure in 33% of exposed pediatric and 14% of exposed reproductive-age patients. Compared with single-agent assessment, summed total CED identified additional patients mainly in the pediatric group, corresponding to relative increases of 20.2% and 0.3%, respectively. Agents not included in the current CED formula accounted for 8.7% of all alkylating-agent prescription records, approximately 90% of which were observed in reproductive-age patients. Conclusions: CED captured alkylating-agent exposure differently by age group: summed CED added exposure information mainly in pediatric patients, whereas agents lacking conversion coefficients limited exposure capture in reproductive-age females. These findings support refinement of CED-based assessment while emphasizing exposure capture, not outcome prediction.