INTRATUMORAL DIFFERENCES IN METHOTREXATE LEVELS WITHIN HUMAN OSTEOSARCOMA XENOGRAFTS STUDIED BY MICRODIALYSIS

A central tenet in oncology is the assumed relationship between drug c oncentration and cytotoxicity. Determinations of drug levels in tumor tissues are, however, generally not undertaken. Microdialysis is a met hod where continuous drug monitoring may be achieved by sampling of lo w molecular weight substances from the extracellular space. By employi ng this technique it is possible to observe variable drug levels withi n tissues, including tumors, over time. Herein, we present results fro m a nude rat model where subcutaneous human osteosarcoma xenografts we re established prior to the administration of the antifolate methotrex ate as an intravenous infusion. Significant differences in drug exposu re within single tumors were evident. Generally, peak drug concentrati ons were lower and drug efflux slower from the center of the tumors as compared to the periphery. The use of microdialysis could be an impor tant tool for optimizing current strategies in anticancer chemotherapy . (C) 1997 Elsevier Science Inc.