Treatment of primary osteosarcoma with intra-arterial and intravenous high-dose methotrexate

In an effort to achieve high concentrations and prolonged exposure times, high-dose methotrexate (MTX) was administered by the intra-arterial route over 6 hours at a dose of 12.5 g/m2 to nine patients with osteosarcoma. This was followed by citrovorum factor (CF) rescue, which was initiated 12 hours after completion of the infusion (MTX-CF). The regimen achieved high local concentrations over a finite period. No toxicity was encountered. Treatment was administered at weekly intervals, during which intravenous MTX-CF was interposed if facilities for intra-arterial administration were not available. However, despite increases in local venous concentrations and exposure times, only four of nine patients (44%) responded. This is similar to responses achieved with 7.5 g/m2 (48%) with CF initiated 2 hours after completion of the infusion. Higher MTX doses, intra-arterial administration, and prolongation of cytotoxic exposure time did not confer a therapeutic advantage as opposed to "conventional" intravenous high doses.