Local and sustained delivery of 5-fluorouracil from biodegradable microspheres for the radiosensitization of malignant glioma: a randomized phase II trial

Neurosurgery. 2005 Feb;56(2):242-8; discussion 242-8. doi: 10.1227/01.neu.0000144982.82068.a2.

Abstract

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.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / therapeutic use*
  • Biodegradation, Environmental
  • Combined Modality Therapy
  • Delayed-Action Preparations
  • Female
  • Fluorouracil / administration & dosage*
  • Glioma / drug therapy*
  • Glioma / radiotherapy*
  • Humans
  • Male
  • Microspheres*
  • Middle Aged
  • Radiation-Sensitizing Agents
  • Supratentorial Neoplasms / drug therapy*
  • Supratentorial Neoplasms / radiotherapy*

Substances

  • Antimetabolites, Antineoplastic
  • Delayed-Action Preparations
  • Radiation-Sensitizing Agents
  • Fluorouracil