Phase II trial of pre-irradiation and concurrent temozolomide in patients with newly diagnosed anaplastic oligodendrogliomas and mixed anaplastic oligoastrocytomas: RTOG BR0131

¹ Brain Tumor and NeuroOncology Center / ND40, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, USA
² Radiation Therapy Oncology Group, Philadelphia, PA, USA
³ Cleveland Clinic, Brain Tumor and NeuroOncology Center, Cleveland, OH, USA
⁴ London Regional Cancer Center, London, Ontario, Canada
⁵ Mayo Clinic, Rochester, MN, USA
⁶ Johns Hopkins School of Medicine, Baltimore, MD, USA
⁷ University of Utah Huntsman Cancer Center, Salt Lake City, UT, USA
⁸ Arizona Oncology Services, Phoenix AZ, USA
⁹ Medical College of Wisconsin, Milwaukee, WI, USA
¹⁰ University of Wisconsin Department of Human Oncology, Madison, WI, USA

^* To whom correspondence should be addressed. E-mail: vogelbm{at}ccf.org.

	Abstract

Purpose: The primary objectives of this phase II study were to evaluate the use of pre-irradiation temozolomide followed by concurrent temozolomide and RT in patients with newly diagnosed anaplastic oligodendroglioma (AO) and mixed anaplastic oligoastrocytoma (MOA). Methods: Pre-irradiation temozolomide (150 mg/m2/day) was given on a 7–day on/7–day off schedule for up to 6 cycles. The primary endpoint was the response rate during the 6–month pre-RT chemotherapy. Tumor tissue was analyzed for the presence of chromosomal deletions on 1p and 19q, and for MGMT promoter methylation. Results: Forty-two patients were enrolled; 39 were eligible. The objective response rate was 32% (6% CR, 26% PR) and the rate of progression during pre-RT chemotherapy was 10%. The worst non-hematological toxicity was grade 4 in 3 patients (8%). Twenty-two patients completed concurrent chemotherapy and RT. There were no grade 4 non-hematological toxicities during the concurrent chemotherapy and RT. Seventeen of 28 (60.7%) evaluable cases had codeletion of 1p/19q; all 17 were free from progression at 6 months. Sixteen of 20 (80%) evaluable cases had MGMT promoter methylation; all 16 were free from progression at 6 months. Conclusions: The rate of progression of 10% during pre-RT temozolomide chemotherapy for newly diagnosed AO and MAO compared favorably to prior experience with pre-RT PCV chemotherapy (20% in RTOG 9402). The toxicity of the dose-intense pre-RT regimen used in this study may warrant evaluation of other, less intense dosing strategies. Future studies will need to prospectively stratify patients according to the presence of deletions of chromosomes 1p and 19q.

Key Words: 1p/19q loss of heterozygosity, MGMT, glioma, oligodendroglioma, RTOG, temozolomide

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