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 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.