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

INTRODUCTION: Carmustine (BCNU)-impregnated biodegradable polymer wafers have been shown to prolong survival in patients with recurrent malignant glioma. Interferon alfa-2b (IFNalpha(2b)) 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 IFNalpha(2b) 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, IFNalpha(2b) was initiated three times a week at a dose of 3 MU/m(2), which was escalated in increments of 3 MU/m(2). 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/m(2). Two complete imaging responses were observed at the 3 MU/m(2) dose. MGMT expression and gene expression arrays did not correlate with toxicity or response.
CONCLUSIONS: Multimodal therapy with surgery, BCNU wafers, and IFNalpha(2b) appears to be a feasible and safe treatment strategy. The maximum tolerated dose of IFNalpha(2b) was determined to be 6 MU/m(2). Analysis of MGMT expression and gene expression was feasible.