1. Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study
- Author
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Baumert, BG, Hegi, ME, van den Bent, MJ, von Deimling, A, Gorlia, T, Hoang-Xuan, K, Brandes, AA, Kantor, G, Taphoorn, MJB, Ben Hassel, M, Hartmann, C, Ryan, G, Capper, D, Kros, JM, Kurscheid, S, Wick, W, Enting, R, Reni, M, Thiessen, B, Dhermain, F, Bromberg, JE, Feuvret, L, Reijneveld, JC, Chinot, O, Gijtenbeek, JMM, Rossiter, JP, Dif, N, Balana, C, Bravo-Marques, J, Clement, PM, Marosi, C, Tzuk-Shina, T, Nordal, RA, Rees, J, Lacombe, D, Mason, WP, Stupp, R, Baumert, BG, Hegi, ME, van den Bent, MJ, von Deimling, A, Gorlia, T, Hoang-Xuan, K, Brandes, AA, Kantor, G, Taphoorn, MJB, Ben Hassel, M, Hartmann, C, Ryan, G, Capper, D, Kros, JM, Kurscheid, S, Wick, W, Enting, R, Reni, M, Thiessen, B, Dhermain, F, Bromberg, JE, Feuvret, L, Reijneveld, JC, Chinot, O, Gijtenbeek, JMM, Rossiter, JP, Dif, N, Balana, C, Bravo-Marques, J, Clement, PM, Marosi, C, Tzuk-Shina, T, Nordal, RA, Rees, J, Lacombe, D, Mason, WP, and Stupp, R
- Abstract
BACKGROUND: Outcome of low-grade glioma (WHO grade II) is highly variable, reflecting molecular heterogeneity of the disease. We compared two different, single-modality treatment strategies of standard radiotherapy versus primary temozolomide chemotherapy in patients with low-grade glioma, and assessed progression-free survival outcomes and identified predictive molecular factors. METHODS: For this randomised, open-label, phase 3 intergroup study (EORTC 22033-26033), undertaken in 78 clinical centres in 19 countries, we included patients aged 18 years or older who had a low-grade (WHO grade II) glioma (astrocytoma, oligoastrocytoma, or oligodendroglioma) with at least one high-risk feature (aged >40 years, progressive disease, tumour size >5 cm, tumour crossing the midline, or neurological symptoms), and without known HIV infection, chronic hepatitis B or C virus infection, or any condition that could interfere with oral drug administration. Eligible patients were randomly assigned (1:1) to receive either conformal radiotherapy (up to 50·4 Gy; 28 doses of 1·8 Gy once daily, 5 days per week for up to 6·5 weeks) or dose-dense oral temozolomide (75 mg/m2 once daily for 21 days, repeated every 28 days [one cycle], for a maximum of 12 cycles). Random treatment allocation was done online by a minimisation technique with prospective stratification by institution, 1p deletion (absent vs present vs undetermined), contrast enhancement (yes vs no), age (<40 vs ≥40 years), and WHO performance status (0 vs ≥1). Patients, treating physicians, and researchers were aware of the assigned intervention. A planned analysis was done after 216 progression events occurred. Our primary clinical endpoint was progression-free survival, analysed by intention-to-treat; secondary outcomes were overall survival, adverse events, neurocognitive function (will be reported separately), health-related quality of life and neurological function (reported separately), and correlative analyses of progres
- Published
- 2016