Phase I analysis of BCNU-impregnated biodegradable polymer wafers followed by systemic interferon alfa-2b in adults with recurrent glioblastoma multiforme

Jeffrey J. Olson*, Ellen McKenzie, Megan Skurski-Martin, Zhaobin Zhang, Daniel Brat, Surasak Phuphanich

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Introduction: Carmustine (BCNU)-impregnated biodegradable polymer wafers have been shown to prolong survival in patients with recurrent malignant glioma. Interferon alfa-2b (IFNα2b) has demonstrated antitumor activity against a number of cancers, but its use in glioma has been limited. The use of these agents in combination is appealing because the mode of antitumor activity likely differs. This is a report of a phase I dose-finding study for IFNα2b in combination with surgery and BCNU wafers in patients with recurrent glioblastoma. Method: Patients with progressive malignant glioma that was confirmed intraoperatively to be glioblastoma were treated with surgical resection and implantation of 8 BCNU wafers. A week later, IFNα2b was initiated three times a week at a dose of 3 MU/m2, which was escalated in increments of 3 MU/m2. The treatment cycle encompassed 8 weeks. Toxicity was monitored by clinical and laboratory testing. Correlative studies of methylguanine methyltransferase (MGMT) expression and gene expression array analysis were carried out. Results: Ten patients were enrolled, and 9 patients had evaluable data. Dose-limiting toxicity in the form of fatigue occurred at 9 MU/m2. Two complete imaging responses were observed at the 3 MU/m2 dose. MGMT expression and gene expression arrays did not correlate with toxicity or response. Conclusions: Multimodal therapy with surgery, BCNU wafers, and IFNα2b appears to be a feasible and safe treatment strategy. The maximum tolerated dose of IFNα2b was determined to be 6 MU/m2. Analysis of MGMT expression and gene expression was feasible.

Original languageEnglish (US)
Pages (from-to)293-299
Number of pages7
JournalJournal of Neuro-Oncology
Volume90
Issue number3
DOIs
StatePublished - 2008

Keywords

  • Gene expression array
  • Gliadel wafer
  • Glioblastoma
  • Interferon alfa
  • Methylguanine methyltransferase

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neurology

Fingerprint Dive into the research topics of 'Phase I analysis of BCNU-impregnated biodegradable polymer wafers followed by systemic interferon alfa-2b in adults with recurrent glioblastoma multiforme'. Together they form a unique fingerprint.

  • Cite this