Influence of 5-fluorouracil-loaded microsphere formulation on efficient rat glioma radiosensitization.
OBJECTIVE
To determine (i) the efficiency of radiosensitizing 5-FU-loaded microspheres and (ii) the impact of microparticle formulation on response to treatment.


METHODS
C6 tumor-bearing rats were stereotactically implanted with microspheres and/or allocated to: control groups (untreated) or treatment (only radiotherapy; fast-release 5-FU microspheres + radiotherapy; slow-release 5-FU microspheres + radiotherapy). The next day, fractionated radiotherapy, limited to the hemibrain, was initiated in all treated animals. The irradiation cycle included 36 Gy, given in 9 sessions for 3 consecutive weeks. Tumor development was assessed by T2-weighted MRI.


RESULTS
5-FU microspheres associated with radiotherapy caused a 47% complete remission rate (9/19) as opposed to the 8% rate (1/12) when radiotherapy alone or 0% in control animals. Drug delivery for 3 weeks produced better survival results (57%) compared to one-week sustained release (41%). MR images showed exponentially increasing tumor volumes during the first half of the radiotherapy cycle, followed by a decrease, and the disappearance of the tumor if survival exceeded 120 days.


CONCLUSIONS
5-FU controlled delivery is a promising strategy for radiosensitizing gliomas. Drug delivery system formulation is unambiguously implicated in both the response to treatment and the limitation of toxic side effects.
Roullin
Valérie-Gaëlle
VG
INSERM ERIT-M 0104, 49100 Angers, France.
Mege
Martine
M
Lemaire
Laurent
L
Cueyssac
Jean-Pierre
JP
Venier-Julienne
Marie-Claire
MC
Menei
Philippe
P
Gamelin
Erik
E
Benoit
Jean-Pierre
JP
D000818:Animals; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D004353:Drug Evaluation, Preclinical; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D005910:Glioma / Q000473:pathology / Q000532:radiotherapy*; D008279:Magnetic Resonance Imaging; D008863:Microspheres; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D011838:Radiation-Sensitizing Agents; D005472:Fluorouracil