QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Raizer, J. J. Articles by Abrey, L. E. Search for Related Content PubMed PubMed Citation

Phase 1 study of 28-day, low-dose temozolomide and BCNU in the treatment of malignant gliomas after radiation therapy

Neurology Department, Northwestern Memorial Hospital, Chicago, IL 60611 (J.J.R.); Medical College of Wisconsin, Milwaukee, WI 53226 (M.G.M), Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (M.K., L.E.A); USA

² Address correspondence to Jeffrey J. Raizer, Davee Department of Neurology, Abbott Hall, 710 North Lake Shore Drive, Room 1123, Chicago, IL 60611, USA (j-raizer{at}northwestern.edu).

Abstract

We conducted a study to determine the dose-limiting toxicity of an extended dosing schedule of temozolomide (TMZ) when used with a fixed dose of BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea (carmustine), taking advantage of TMZ's ability to deplete O⁶-alkylguanine-DNA-alkyltransferase and the synergistic activity of these two agents. Patients with malignant gliomas who had undergone radiation therapy were eligible. Patients were treated with TMZ for 28 days, followed by a 28-day rest (1 cycle). The TMZ was started at 50 mg/m² and increased in 10-mg/m² increments; a fixed dose of BCNU (150 mg/m²) was given within 72 h of starting TMZ. A standard phase 1 dose-escalation scheme was used with 3 patients per cohort. Fourteen glioblastoma patients and 10 anaplastic astrocytoma patients were treated. The dose-limiting toxicity was myelosuppression at 90 mg/m² of TMZ. The total number of cycles given was 73 (median number was 2). Six patients (25%) required a dose reduction in BCNU, and six were removed from study for hematologic toxicity after cycle 1; three patients overlapped. The median time to progression and overall survival were, respectively, 82 and 132 weeks for anaplastic astrocytomas and 14 and 69 weeks for glioblastomas. We conclude that the combination of BCNU and the extended dosing schedule of TMZ is feasible and that the maximal tolerated dose of a 28-day course of TMZ is 80 mg/m² when combined with a fixed dose of BCNU at 150 mg/m². This is the recommended dose for phase 2, but myelosuppression after cycle 1 suggests that long-term treatment may be difficult.

This article has been cited by other articles:

				D. S. Ziegler, A. L. Kung, and M. W. Kieran Anti-Apoptosis Mechanisms in Malignant Gliomas J. Clin. Oncol., January 20, 2008; 26(3): 493 - 500. [Abstract] [Full Text] [PDF]

				U. Herrlinger, J. Rieger, D. Koch, S. Loeser, B. Blaschke, R.-D. Kortmann, J. P. Steinbach, T. Hundsberger, W. Wick, R. Meyermann, et al. Phase II Trial of Lomustine Plus Temozolomide Chemotherapy in Addition to Radiotherapy in Newly Diagnosed Glioblastoma: UKT-03 J. Clin. Oncol., September 20, 2006; 24(27): 4412 - 4417. [Abstract] [Full Text] [PDF]

				R. Stupp, M. E. Hegi, M. J. van den Bent, W. P. Mason, M. Weller, R. O. Mirimanoff, J. G. Cairncross, and on behalf of the European Organisation for Researc Changing paradigms--an update on the multidisciplinary management of malignant glioma. Oncologist, February 1, 2006; 11(2): 165 - 180. [Abstract] [Full Text] [PDF]