Local and sustained delivery of 5-fluorouracil from biodegradable microspheres for the radiosensitization of glioblastoma: a pilot study.
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 microm 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 remission 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].
Service de Neurochirurgie, Centre Hospitalo-Universitaire d'Angers, France.
P
P
Menei
M C
MC
Venier
E
E
Gamelin
J P
JP
Saint-André
G
G
Hayek
E
E
Jadaud
D
D
Fournier
P
P
Mercier
G
G
Guy
J P
JP
Benoit
D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D001673:Biodegradation, Environmental; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D016503:Drug Delivery Systems; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D010865:Pilot Projects; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D016019:Survival Analysis; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D011838:Radiation-Sensitizing Agents; D005472:Fluorouracil