The lack of a more dramatic response to chemotherapy of brain tumors has been partially attributed to the blood-brain barrier, or more precisely, the blood-tumor barrier. The effectiveness of chemotherapy agents has traditionally been attributed to their ability to penetrate across the blood-brain barrier, but this remains controversial. We propose to study the tissue delivery of the chemotherapeutic agent paclitaxel into brain tumors by simultaneously assaying (1)serum, (2)cerebrospinal fluid, (3) brain tumor tissue, and (4)brain tissue adjacent to tumor for paclitaxel drug levels following an infusion of paclitaxel. Patients entered into this study will be those patients with recurrent primary brain tumors, or recurrent or newly diagnosed brain metastasis whose normal course of treatment would consist of resection of the tumor. After determining the levels of paclitaxel in tumor tissue, we plan to examine whether or not tamoxifen enhances the delivery of paclitaxel to tumor. The specific objectives of this study are (1)to determine whether therapeutically effective levels of paclitaxel can be achieved in brain tumor tissue following an infusion of chemotherapy; (2)to determine the therapeutic index of paclitaxel drug delivery based upon tissue levels in brain tumor vs. normal brain adjacent to tumor; and (3)to determine whether or not agents that open the blood-brain barrier such as tamoxifen increase the therapeutic index of paclitaxel drug delivery.
Showing the most recent 10 out of 1103 publications
