RTOG 0525: A randomized phase III trial comparing standard adjuvant temozolomide (TMZ) with a dose-dense (dd) schedule in newly diagnosed glioblastoma (GBM).

• DOI: 10.1200/jco.2011.29.15_suppl.2006
• Publication Date: 2017-02-23T13:58:03Z
• Authors: M. R. Gilbert; M. Wang; K. D. Aldape; R. Stupp; M. Hegi; K. A. Jaeckle; T. S. Armstrong; J. S. Wefel; M. Won; D. T. Blumenthal; A. Mahajan; C. J. Schultz; S. C. Erridge; P. D. Brown; A. Chakravarti; W. J. Curran; M. P. Mehta
• Keywords: Temozolomide; Clinical endpoint; Concomitant; Progression-free survival

2006 Background: Radiotherapy with concomitant and adjuvant TMZ (TMZ/RT→TMZ) is the standard of care for newly diagnosed GBM. MGMT methylation status may be an important determinant treatment response. Compared TMZ, dd results in prolonged depletion blood mononuclear cells possibly tumor. This trial determined if intensified improves survival (OS) or progression free (PFS). Methods: phase III was conducted by RTOG, EORTC NCCTG. Neurologically stable patients adequate tissue prospective analysis were randomized to Arm 1: (150-200 mg/m2 x 5 d) 2: (75-100 21 q 4 wks 6-12 cycles. Symptom, QOL neurocognitive testing performed a subset patients. The primary endpoint OS. Secondary analyses evaluated impact status. Eligibility criteria included age > 18 yrs, KPS ≥ 60, block 1cm2 Results: A total 833 from 1173 registered. Inadequate (n=144) early disease (n =56) most frequent reasons non-randomization. No statistical difference observed between Arms 1 2 median OS (16.6, 14.9 mo, p = 0.63), PFS (5.5, 6.7 0.06), associated improved (21.2, 14 < 0.0001), (8.7, 5.7 0.0001) response (p 0.012). Cox modeling showed that RPA class significant predictors while arm radiation technique (EORTC vs. RTOG) not. There increased grade 3 toxicity (19%, 27%, 0.008); mostly lymphopenia fatigue. Conclusions: study did not demonstrate efficacy GBM regardless However, it confirmed prognostic significance Additionally, demonstrated feasibility tumor collection, molecular stratification collection patient outcomes large transatlantic intergroup established this as viable clinical paradigm. Supported NCI U10 CA 21661 CA37422.