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/m2 given as a 4-h infusion) therapy in a 43-year-old man with a malignant fibrous histiocytoma in the medial 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 treatment cycle due to leakage. No attempt to correct for microdialysis recovery was made. The intratumorally localized probe gave reproducible 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 MTX and its major extracellular metabolite 7-hydroxymethotrexate. Although limited to the study of MTX pharmacokinetics in a single subject, the experiment demonstrates that intratumoral microdialysis may provide data on tumor drug exposure, although of an indirect nature and dependent on the probe characteristics, the flow rate, and, possibly, the time after probe implantation. We propose that the application of microdialysis may prove useful for elucidation of the relationship between local drug exposure and the therapeutic response in normally inaccessible compartments during cancer pharmacotherapy.
Ekstrøm
P O
PO
Department of Surgical Oncology, Norwegian Radium Hospital, Oslo, Norway.
Andersen
A
A
Saeter
G
G
Giercksky
K E
KE
Slørdal
L
L
D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005266:Femoral Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D018219:Histiocytoma, Benign Fibrous / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D017551:Microdialysis / Q000379:methods*
D000964:Antimetabolites, Antineoplastic; C011864:7-hydroxymethotrexate; D008727:Methotrexate