Phase 2 trial of BCNU plus irinotecan in adults with malignant glioma.

Abstract

In preclinical studies, BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, plus CPT-11 (irinotecan) exhibits schedule-dependent, synergistic activity against malignant glioma (MG). We previously established the maximum tolerated dose of CPT-11 when administered for 4 consecutive weeks in combination with BCNU administered on the first day of each 6-week cycle. We now report a phase 2 trial of BCNU plus CPT-11 for patients with MG. In the current study, BCNU (100 mg/m2) was administered on day 1 of each 6-week cycle. CPT-11 was administered on days 1, 8, 15, and 22 at 225 mg/m2 for patients receiving CYP3A1- or CYP3A4-inducing anticonvulsants and at 125 mg/m2 for those not on these medications. Newly diagnosed patients received up to 3 cycles before radiotherapy, while recurrent patients received up to 8 cycles. The primary end point of this study was radiographic response, while time to progression and overall survival were also assessed. Seventy-six patients were treated, including 37 with newly diagnosed tumors and 39 with recurrent disease. Fifty-six had glioblastoma multiforme, 18 had anaplastic astrocytoma, and 2 had anaplastic oligodendroglioma. Toxicities (grade > or =3) included infections (13%), thromboses (12%), diarrhea (10%), and neutropenia (7%). Interstitial pneumonitis developed in 4 patients. Five newly diagnosed patients (14%; 95% CI, 5%-29%) achieved a radiographic response (1 complete response and 4 partial responses). Five patients with recurrent MG also achieved a response (1 complete response and 4 partial responses; 13%; 95% CI, 4%-27%). More than 40% of both newly diagnosed and recurrent patients achieved stable disease. Median time to progression was 11.3 weeks for recurrent glioblastoma multiforme patients and 16.9 weeks for recurrent anaplastic astrocytoma/ anaplastic oligodendroglioma patients. We conclude that the activity of BCNU plus CPT-11 for patients with MG appears comparable to that of CPT-11 alone and may be more toxic.

• Authors: David A Reardon, Jennifer A Quinn, Jeremy N Rich, Sridharan Gururangan, James Vredenburgh, John H Sampson, James M Provenzale, Amy Walker, Michael Badruddoja, Sandra Tourt-Uhlig, James E Herndon 2nd, Jeannette M Dowell, Mary Lou Affronti, Susanne Jackson, Deborah Allen, Karen Ziegler, Steven Silverman, Cindy Bohlin, Allan H Friedman, Darell D Bigner, Henry S Friedman
• Journal: Neuro-oncology (Neuro Oncol) Vol. 6 Issue 2 Pg. 134-44 (Apr 2004) ISSN: 1522-8517 [Print] England
• PMID: 15134628 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Irinotecan
• Carmustine
• Camptothecin

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Astrocytoma (drug therapy, pathology)
• Camptothecin (administration & dosage, analogs & derivatives)
• Carmustine (administration & dosage)
• Confidence Intervals
• Female
• Glioblastoma (drug therapy, pathology)
• Glioma (drug therapy, pathology)
• Humans
• Irinotecan
• Male
• Middle Aged
• Oligodendroglioma (drug therapy, pathology)