Local and sustained delivery of 5-fluorouracil from biodegradable microspheres for the radiosensitization of malignant glioma: a randomized phase II trial.
OBJECTIVE
This study was a randomized, multicenter Phase II trial comparing the effect of perioperative implantation of 5-fluorouracil-releasing microspheres followed by early radiotherapy (Arm A) and early radiotherapy alone (Arm B) in patients with gross total resection of high-grade glioma.


METHODS
Patients were randomized on clinical and radiological assumption of supratentorial high-grade glioma. All patients underwent surgery, and after resection and histological confirmation, patients randomized to Arm A received multiple injections of microsphere suspension (130 mg of 5-fluorouracil). Conventional fractionated radiotherapy (59.4 Gy) was initiated between the second and the seventh day after surgery for both arms.


RESULTS
A total of 95 patients were randomized. Seventy-seven patients were treated and analyzed in intention to treat for efficacy and safety. Overall survival was 15.2 months in Arm A and 13.5 months in Arm B. In the subpopulation of patients with complete resection, overall survival was 15.2 months in Arm A versus 12.3 months in Arm B. However, these differences were not significant. Safety was acceptable with prophylactic high doses of corticosteroids.


CONCLUSIONS
It may be hypothesized that the implantation of 5-fluorouracil-loaded microspheres in the wall of the cavity resection did increase the overall survival, but the present study was not designed and sufficiently powered to demonstrate this.
Menei
Philippe
P
Department of Neurosurgery, Institut National de la Santé et de la Recherche Médicale, Unite 646, University Hospital, Angers, France. phmenei@chu-angers.fr
Capelle
Laurent
L
Guyotat
Jacques
J
Fuentes
Stéphane
S
Assaker
Richard
R
Bataille
Benoit
B
François
Patrick
P
Dorwling-Carter
Didier
D
Paquis
Philippe
P
Bauchet
Luc
L
Parker
Fabrice
F
Sabatier
Jean
J
Faisant
Nathalie
N
Benoit
Jean-Pierre
JP
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001673:Biodegradation, Environmental; D003131:Combined Modality Therapy; D003692:Delayed-Action Preparations; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D005910:Glioma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D011838:Radiation-Sensitizing Agents; D015173:Supratentorial Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*
D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D011838:Radiation-Sensitizing Agents; D005472:Fluorouracil