Nguyen Thi Hoai Ly, Nguyen Van Thang, Phan Quynh Lan, Nguyen Le Trang, Nguyen Vu Hai Ngoc, Tran Thi Thu Trang, Nguyen Tu Son

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Abstract

Objective: To describe current high-dose methotrexate use in osteosarcoma patients at Vinmec Times City Hospital from January 2023 to September 2025, as a basis for developing a standardized protocol with clinical pharmacist involvement. Methods: A retrospective cohort study was conducted using medical records of osteosarcoma patients receiving methotrexate at doses ≥500 mg/m². The HD-MTX process was described at predefined points: pre-infusion, infusion start, and 4, 24, 48, 72, and x hours after infusion. Results: A total of 342 cycles from 45 patients were analyzed. Complete pre-infusion laboratory assessment was performed in 73.1% of cycles. All cycles received hydration and urinary alkalinization, and achieved urine pH ≥7. However, 11.4% had alkalinization duration < 4 hours, 46.8% had Tpre NaHCO₃ < 40 mEq/L, and only 33.6% achieved infusion rate ≥125 mL/m²/h. MTX target concentrations were achieved in 75.1%, 97.0%, and 53.0% at T₂₄, T₄₈, and T₇₂, respectively; median Tₓ was 69 hours. Adverse events occurred in 303/342 cycles (88.6%), mainly vomiting (27.8%), nausea (23.7%), elevated AST (73.9%) and ALT (66.2%). Conclusion: HD-MTX use remained suboptimal regarding alkalinization duration, NaHCO₃ dosing, infusion rate, and management of supratherapeutic MTX levels. A standardized protocol and proactive monitoring model with clinical pharmacist participation are needed.