Treatment > Irinotecan · Temozolomide Clinical Trials

Meeting Abstract

Treatment of adults with recurrent malignant glioma using temozolomide plus CPT-11: a phase I study

Sandra Tourt-Uhlig, David Reardon, Mary L Affronti, Deborah Allen, Rodney Beason, Brandon Evans, Sridharan Gururangan, Allan Friedman, Susanne Jackson, Roger McLendon, Jennifer Quinn, Jeremy Rich, John Sampson, Valerie Stafford-Fox, Karen Ziegler, Darell D Bigner, Henry Friedman

Duke University Med Ctr, Durham, NC; Pharmacia Corporation, Kalamazoo, MI; Schering-Plough, Kenilworth, NJ

The combination of temozolomide plus CPT-11 produced greater than additive activity when given to athymic nude mice with a D-54 malignant glioma (MG) xenograft (Patel, Clin Ca Res 6:4154, 2000). 
These results led to the current phase I study combining temozolomide with CPT-11 for patients with recurrent MG. 
In this study, patients were stratified by whether they were concurrently taking glucouronidation-enhancing anti-convulsant (GEAC) or not. 
Temozolomide is administered at 200 mg/m2/day for 5 consecutive days beginning on the same day as the first CPT-11 dose. CPT-11 is administered intravenously once weekly over 90 minutes. 
A treatment cycle consists of 4 weekly administrations of CPT-11 followed by a two-week rest. 
The dose of CPT-11 escalates in cohorts of 3-6 patients beginning at 40 mg/m2. 
Twenty-four patients have been treated to date including 17 receiving concurrent GEACs (glioblastoma multiforme (GBM), n=17; anaplastic astrocytoma (AA), n=3) and 7 not taking GEACs (GBM, n=4; AA, n=3). 
No DLT has been encountered to date and accrual is ongoing at the 100 mg/m2 dose level for patients on GEAC and at the 80 mg/m2 dose level for those not receiving GEACs. 
Thirteen of 20 evaluable patients have had stable disease for at least 2 cycles. 
Based on these encouraging results, a phase II study is planned once the current studies establish the MTDs for each treatment strata.

© Copyright 2002 American Society of Clinical Oncology