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Local and sustained delivery of 5‐fluorouracil from biodegradable microspheres for the radiosensitization of glioblastoma
Author(s) -
Menei Philippe,
Venier MarieClaire,
Gamelin Erik,
SaintAndré JeanPaul,
Hayek Ghassan,
Jadaud Eric,
Fournier Dominique,
Mercier Philippe,
Guy Gilles,
Benoit JeanPierre
Publication year - 1999
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19990715)86:2<325::aid-cncr17>3.0.co;2-s
Subject(s) - medicine , drug delivery , antimetabolite , microsphere , fluorouracil , glioblastoma , surgery , radiation therapy , magnetic resonance imaging , cerebrospinal fluid , radiosurgery , radiosensitizer , chemotherapy , urology , nuclear medicine , radiology , cancer research , chemistry , organic chemistry , chemical engineering , engineering
BACKGROUND The authors have developed a new method of drug delivery into the brain using implantable biodegradable microspheres. In this study, this method was used to provide localized and sustained delivery of 5‐fluorouracil (5‐FU) after the surgical resection of glioblastoma. This antimetabolite and radiosensitizing drug was selected in an attempt to decrease the rate of local recurrence of the tumor. METHODS Eight patients with newly diagnosed glioblastoma were included in the study and 2 increasing amounts of 5‐FU were studied (70 mg and 132 mg). After surgical resection of the tumor, poly(D‐L lactide‐co‐glycolide) 5‐FU‐loaded microspheres with an average dimension of 45 µm were implanted in the wall of the surgical bed. External beam radiation (59.4 grays) was initiated before the seventh postsurgical day. Patients were followed by clinical examination, magnetic resonance imaging, and 5‐FU assays in the blood and cerebrospinal fluid (CSF). RESULTS 5‐FU assays confirmed sustained concentrations in the CSF for at least 1 month. Concentrations of 5‐FU in the blood were lower and transitory. Systemic tolerance to the treatment was good; one case of recurrent brain swelling was observed at the higher dose studied. At the time of last follow‐up the overall median survival time was 98 weeks from the time of implantation and 2 patients had achieved disease remision at 139 and 153 weeks, respectively. CONCLUSIONS This study demonstrates that biodegradable microspheres are efficient systems for drug delivery into the brain and may have future application in the treatment of brain tumors. Further studies are needed to confirm the potential of 5‐FU‐loaded microspheres for the radiosensitization of glioblastoma. [Please see editorial on pages 197‐9, this issue]. Cancer 1999;86:325–30. © 1999 American Cancer Society.