Phase I/II Trial of Gliadel Plus Temodar for Adult Patients with Recurrent High-Grade Glioma.
Jeremy Rich, David Reardon, Deborah Allen, Mary Lou Affronti, James Carter, Shari Edwards, Allan Friedman, Sri Gururangan, James Herndon, Suzanne Jackson, Roger McLendon, Jennifer Quinn, Sandra Tourt-Uhlig, John Sampson, Darell Bigner, Valerie Stafford-Fox, Sara Zaknoen, Henry Friedman, Duke University Medical Center, Durham, NC; Oncology Biotech, Chapel Hill, NC; Schering-Plough Research Institute, Kenilworth, NJ.
Presented at the American Society Of Clinical Oncology, 2001 Conference

Gliadel wafers, an FDA-approved treatment for patients with high-grade gliomas (HGG) deliver interstitial chemotherapy directly to the primary site via controlled release polymers containing 3.85% BCNU. However, because HGG tend to aggressively infiltrate, we hypothesized that combining Gliadel wafers with systemic chemotherapy may improve overall tumor control. We therefore are conducting a Phase I/II study combining Temodar, an oral imidazotetrazine alkylating agent with established activity against recurrent and newly diagnosed HGG, with Gliadel wafers for patients with recurrent HGG. Gliadel wafers (as many as possible, to a maximum of 8) are implanted in the resected tumor cavity at the time of surgery. Treatment with Temodar starts within 14-21 days of surgery and is administered for 5 consecutive days every 28 days. Patients may receive up to a maximum of 12 cycles of Temodar in the absence of progressive disease or unacceptable toxicity. In the Phase I study, the initial Temodar dose was 100 mg/m2/day and dose escalations were successfully conducted to 200 mg/m2/day without dose-limiting toxicity. Accrual in the Phase II study is ongoing at a Temodar dose of 200 mg/m2/day. Thirteen patients have been enrolled to date including 9 with GBM and 4 with AA. Toxicity has been mild and primarily hematologic with only one patient sustaining a reversible grade 4 hematologic toxicity. Nine patients have achieved stable disease for 1-12 cycles of Temodar. Our results demonstrate that Gliadel followed by Temodar appears to be well tolerated with encouraging although preliminary response rates.