BACKGROUND: The authors developed a new method of drug delivery into the brain using implantable, biodegradable microspheres. The strategy was evaluated initially to provide localized and sustained delivery of the radiosensitizer 5-fluorouracil (5-FU) after patients underwent surgical resection of malignant glioma. In this study, the microspheres were implanted by stereotaxy into deeply situated and inoperable brain tumors. METHODS: Ten patients with newly diagnosed, inoperable, malignant gliomas were included in the study, and 1 dose of 5-FU was studied (132 mg). After histologic confirmation, a suspension of poly(D-L lactide-co-glycolide) 5-FU-loaded microspheres was implanted by stereotaxy into the tumor in one or several trajectories with one to seven deposits per trajectory. External beam radiation (59.4 grays) was started before postoperative Day 7. Patients were followed by clinical examination, computed tomography scanning, magnetic resonance imaging, and 5-FU assays in blood and cerebrospinal fluid (CSF). RESULTS: The number of trajectories was adapted to the size and shape of the tumor. Microsphere implantation was tolerated well, except in four patients who received a single trajectory and experienced a transitory worsening of preexisting neurologic symptoms. There were no episodes of edema or hematologic complications. 5-FU was detected in CSF and blood in some patients at very low concentrations. The median overall survival was 40 weeks, with 2 patients who had longer survival (71 weeks and 89 weeks, respectively). CONCLUSIONS: In this study, the authors demonstrated that biodegradable microspheres could be implanted by stereotaxy and were efficient systems for drug delivery into brain tumors. This method may have future applications in the treatment of patients other malignancies. Copyright 2003 American Cancer Society.
BACKGROUND: The authors developed a new method of drug delivery into the brain using implantable, biodegradable microspheres. The strategy was evaluated initially to provide localized and sustained delivery of the radiosensitizer 5-fluorouracil (5-FU) after patients underwent surgical resection of malignant glioma. In this study, the microspheres were implanted by stereotaxy into deeply situated and inoperable brain tumors. METHODS: Ten patients with newly diagnosed, inoperable, malignant gliomas were included in the study, and 1 dose of 5-FU was studied (132 mg). After histologic confirmation, a suspension of poly(D-L lactide-co-glycolide) 5-FU-loaded microspheres was implanted by stereotaxy into the tumor in one or several trajectories with one to seven deposits per trajectory. External beam radiation (59.4 grays) was started before postoperative Day 7. Patients were followed by clinical examination, computed tomography scanning, magnetic resonance imaging, and 5-FU assays in blood and cerebrospinal fluid (CSF). RESULTS: The number of trajectories was adapted to the size and shape of the tumor. Microsphere implantation was tolerated well, except in four patients who received a single trajectory and experienced a transitory worsening of preexisting neurologic symptoms. There were no episodes of edema or hematologic complications. 5-FU was detected in CSF and blood in some patients at very low concentrations. The median overall survival was 40 weeks, with 2 patients who had longer survival (71 weeks and 89 weeks, respectively). CONCLUSIONS: In this study, the authors demonstrated that biodegradable microspheres could be implanted by stereotaxy and were efficient systems for drug delivery into brain tumors. This method may have future applications in the treatment of patients other malignancies. Copyright 2003 American Cancer Society.
Authors: Brent D Weinberg; Ravi B Patel; Hanping Wu; Elvin Blanco; Carlton C Barnett; Agata A Exner; Gerald M Saidel; Jinming Gao Journal: Med Biol Eng Comput Date: 2008-06-04 Impact factor: 2.602