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

BACKGROUND

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.

METHODS

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.