Progression of osteosarcoma after high-dose methotrexate: over-rescue by folinic acid

A 16-year-old girl with a distal femur osteosarcoma became pain-free with the first treatment of methotrexate 12.5 g/m(2) and folinic acid 760 mg/m(2). She was inadvertently given 1275 mg folinic acid after the third dose. Four days later, pain and swelling recurred. Appreciating that this was "over rescue" rather than drug resistance led to the successful use of a further 8 doses of high-dose methotrexate when a suboptimal response was achieved with cisplatinum, Adriamycin, and ifosfamide. This is the first time "over rescue" has been documented in humans from high-dose folinic acid after methotrexate.