CONTINUOUS INTRATUMORAL MICRODIALYSIS DURING HIGH-DOSE METHOTREXATE THERAPY IN A PATIENT WITH MALIGNANT FIBROUS HISTIOCYTOMA OF THE FEMUR -A CASE-REPORT

We used a microdialysis technique to assay intratumoral methotrexate ( MTX) levels during high-dose (12 g/m(2) given as a 4-h infusion) thera py in a 43-year-old man with a malignant fibrous histiocytoma in the m edial femoral condyle. Additional microdialysis probes were implanted in muscle tissue contralateral to the tumor and in an antecubital vein . Microdialysis was attempted during the initial two high-dose courses , but the two latter probes were removed at the start of the second tr eatment cycle due to leakage. No attempt to correct for microdialysis recovery was made. The intratumorally localized probe gave reproducibl e data on tumor MTX exposure of 9.3-14% of unbound systemic MTX. There was a close correlation between tumor and systemic levels for both MT X and its major extracellular metabolite 7-hydroxymethotrexate. Althou gh limited to the study of MTX pharmacokinetics in a single subject, t he experiment demonstrates that intratumoral microdialysis may provide data on tumor drug exposure, although of an indirect nature and depen dent on the probe characteristics, the flow rate, and, possibly, the t ime after probe implantation. We propose that the application of micro dialysis may prove useful for elucidation of the relationship between local drug exposure and the therapeutic response in normally inaccessi ble compartments during cancer pharmacotherapy.