RTOG 0131: Phase II trial of pre-irradiation and concurrent temozolomide in patients with newly diagnosed anaplastic oligodendrogliomas and mixed anaplastic oligodendrogliomas

Abstract

1520 Background: RTOG 9402 showed that a dose-intense pre-radiation chemotherapy regimen consisting of procarbazine, lomustine and vincristine (PCV) for anaplastic oligodendrogliomas (AOs) and mixed anaplastic oligoastrocytomas (MAOs) produced improved progression free survival at the expense of increased toxicity, but no improvement in overall survival. A less toxic chemotherapy, temozolomide (TMZ), has also shown efficacy in several glial tumors, and it can be given concurrently with radiation therapy (RT) with acceptable toxicity. Methods: A phase II study was performed to evaluate the efficacy of pre-RT TMZ and the toxicity of concurrent RT and TMZ in patients with newly diagnosed AO or MAO. The primary endpoint was to determine the pre-RT TMZ six-month progression rate. Results: 40 eligible patients were entered into the trial; 55% were male, median age was 45, 50% had an AO. Twenty-seven patients completed 6 months of pre-RT TMZ and have undergone central review, and three are too early to evaluate. Of the remaining ten patients, two withdrew early due to tumor progression (not reviewed) and 4 withdrew due to toxicity. Four other patients withdrew from study without evidence of toxicity or progression. Pre-RT TMZ responses in centrally-reviewed patients (N = 27) were as follows: 1 CR (3.7%), 8 PR (29.6%), 15 SD (55.6%) and 1 PD (3.7%). CR required resolution of both T1 and T2 changes. Two patients (7.4%) had no evaluable disease. If the 2 patients who withdrew due to reported progression are included, the 6-month progression rate is 3/29 (10.3%). During concurrent RT and TMZ treatment there were two (5%) grade 3 and zero grade 4 non-hematologic toxicities. Conclusions: Pre-RT TMZ appears to be feasible, without an inordinately high rate of early progression (10.3%). In comparison, the overall 6-month progression rate observed in the pre-RT PCV arm of RTOG 9402 was 20%. Toxicity of the concurrent RT and TMZ regimen was acceptable. Analysis of tumor 1p/19q status is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering Oncology