Selected applications of methotrexate alone and in combination in osteosarcoma.

Review of the reported use of high-dose methotrexate (HDMTX) with citrovorum factor rescue (CF) for treatment of primary and metastatic osteosarcoma indicates the rarity of responses in clinical situations other than treatment of the primary tumor or isolated pulmonary metastases with doses of 7.5 g/m2 or greater delivered on a weekly basis for 4 to 6 weeks. Adjuvant chemotherapy using HDMTX-CF at triweekly intervals has led to 2-year disease-free survival rates that are inferior to those obtained with combinations of agents including HDMTX-CF Adriamycin (Adria), with or without vincristine, cyclophosphamide, phenylalanine mustard, bleomycin, and dactinomycin. We concluded that although HDMTX-CF has a role in the treatment of primary and metastatic osteosarcoma, its use in combination with other active agents offers greater potential advantage to affected patients.