Publications [#132207] of James M Provenzale

Papers Published

1. DA Reardon, JA Quinn, JN Rich, S Gururangan, J Vredenburgh, JH Sampson, JM Provenzale, A Walker, M Badruddoja, S Tourt-Uhlig, JE Herndon 2nd, JM Dowell, ML Affronti, S Jackson, D Allen, K Ziegler, S Silverman, C Bohlin, AH Friedman, DD Bigner, HS Friedman, Phase 2 trial of BCNU plus irinotecan in adults with malignant glioma., Neuro-oncology, vol. 6 no. 2 (April, 2004), pp. 134-44, ISSN 1522-8517
   (last updated on 2011/07/12)

   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.

   Keywords:
   Adult • Aged • Antineoplastic Combined Chemotherapy Protocols • Astrocytoma • Camptothecin • Carmustine • Confidence Intervals • Female • Glioblastoma • Glioma • Humans • Male • Middle Aged • Oligodendroglioma • administration & dosage • administration & dosage* • analogs & derivatives* • drug therapy • drug therapy* • pathology