Phase II trial of preirradiation and concurrent temozolomide in patients with newly diagnosed anaplastic oligodendrogliomas and mixed anaplastic oligoastrocytomas: RTOG BR0131.

Abstract	The primary objectives of this phase II study were to evaluate the use of preirradiation temozolomide followed by concurrent temozolomide and radiotherapy (RT) in patients with newly diagnosed anaplastic oligodendroglioma (AO) and mixed anaplastic oligoastrocytoma (MOA). Preirradiation temozolomide (150 mg/m(2)/day) was given on a 7-day-on/7-day-off schedule for up to six cycles. The primary end point 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. Forty-two patients were enrolled; 39 were eligible. The objective response rate was 32% (6% [complete response, CR], 26% [partial response PR]), and the rate of progression during pre-RT chemotherapy was 10%. The worst nonhematological toxicity was grade 4 in three patients (8%). Twenty-two patients completed concurrent chemotherapy and RT. There were no grade 4 nonhematological 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. In conclusion, the rate of progression of 10% during pre-RT temozolomide chemotherapy for newly diagnosed AO and MAO compared favorably with 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.
Authors	Michael A Vogelbaum, Brian Berkey, David Peereboom, David Macdonald, Caterina Giannini, John H Suh, Robert Jenkins, James Herman, Paul Brown, Deborah T Blumenthal, Christopher Biggs, Christopher Schultz, Minesh Mehta
Journal	Neuro-oncology (Neuro Oncol) Vol. 11 Issue 2 Pg. 167-75 (Apr 2009) ISSN: 1522-8517 [Print] England
PMID	18779504 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
Chemical References	Antineoplastic Agents, Phytogenic Tumor Suppressor Proteins Dacarbazine DNA Modification Methylases MGMT protein, human DNA Repair Enzymes Temozolomide
Topics	Adolescent Adult Aged Antineoplastic Agents, Phytogenic (therapeutic use) Astrocytoma (diagnosis, drug therapy, radiotherapy, therapy) Brain Neoplasms (diagnosis, drug therapy, radiotherapy, therapy) Chromosome Deletion Chromosomes, Human, Pair 1 (genetics) Chromosomes, Human, Pair 19 (genetics) Combined Modality Therapy DNA Methylation DNA Modification Methylases (genetics) DNA Repair Enzymes (genetics) Dacarbazine (analogs & derivatives, therapeutic use) Dose Fractionation, Radiation Female Humans In Situ Hybridization, Fluorescence Male Middle Aged Neoplasm Recurrence, Local (diagnosis, therapy) Oligodendroglioma (diagnosis, drug therapy, radiotherapy, therapy) Prognosis Promoter Regions, Genetic Survival Rate Temozolomide Treatment Outcome Tumor Suppressor Proteins (genetics) Young Adult

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