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Neurosurgery 56: 242-248, 2005
Local and Sustained Delivery of 5-Fluorouracil from Biodegradable Microspheres for the Radiosensitization of Malignant Glioma: A Randomized Phase II Trial
Philippe Menei, M.D., Ph.D.; Laurent Capelle, M.D.; Jacques Guyotat, M.D., Ph.D.; Stéphane Fuentes, M.D.; Richard Assaker, M.D.; Benoit Bataille, M.D.; Patrick François, M.D.; Didier Dorwling-Carter, M.D.; Philippe Paquis, M.D.; Luc Bauchet, M.D.; Fabrice Parker, M.D.; Jean Sabatier, M.D.; Nathalie Faisant, Ph.D.; Jean-Pierre Benoit, Pharm.D., Ph.D.
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.
CONCLUSION;
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.