Publications [#132219] of James M Provenzale

Papers Published

1. JA Quinn, A Desjardins, J Weingart, H Brem, ME Dolan, SM Delaney, J Vredenburgh, J Rich, AH Friedman, DA Reardon, JH Sampson, AE Pegg, RC Moschel, R Birch, RE McLendon, JM Provenzale, S Gururangan, JE Dancey, J Maxwell, S Tourt-Uhlig, JE Herndon 2nd, DD Bigner, HS Friedman, Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma., Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol. 23 no. 28 (October, 2005), pp. 7178-87, ISSN 0732-183X [doi]
   (last updated on 2011/07/12)

   Abstract:
   OBJECTIVE: We conducted a two-phase clinical trial in patients with progressive malignant glioma (MG). The first phase of this trial was designed to determine the dose of O6-BG effective in producing complete depletion of tumor AGT activity for 48 hours. The second phase of the trial was designed to define the maximum tolerated dose (MTD) of a single dose of temozolomide when combined with O6-BG. In addition, plasma concentrations of O6-BG and O6-benzyl-8-oxoguanine were evaluated after O6-BG. METHODS: For our first phase of the clinical trial, patients were scheduled to undergo craniotomy for AGT determination after receiving a 1-hour O6-BG infusion at 120 mg/m2 followed by a continuous infusion at an initial dose of 30 mg/m2/d for 48 hours. The dose of the continuous infusion of O6-BG escalated until tumor AGT was depleted. Once the O6-BG dose was established a separate group of patients was enrolled in the second phase of clinical trial, in which temozolomide, administered as a single dose at the end of the 1-hour O6-BG infusion, was escalated until the MTD was determined. RESULTS: The O6-BG dose found to be effective in depleting tumor AGT activity at 48 hours was an IV bolus of 120 mg/m2 over 1 hour followed by a continuous infusion of 30 mg/m2/d for 48 hours. On enrolling 38 patients in six dose levels of temozolomide, the MTD was established at 472 mg/m2 with dose-limiting toxicities limited to myelosuppression. CONCLUSIONS: This study provides the foundation for a phase II trial of O6-BG plus temozolomide in temozolomide-resistant MG.

   Keywords:
   Adult • Aged • Antineoplastic Combined Chemotherapy Protocols • Brain Neoplasms • Dacarbazine • Disease Progression • Female • Glioma • Guanine • Humans • Infusions, Intravenous • Injections, Intravenous • Male • Maximum Tolerated Dose • Middle Aged • administration & dosage • adverse effects • analogs & derivatives • drug therapy* • pathology • pharmacokinetics • therapeutic use*