Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma.

Journal Article (Journal Article)

BACKGROUND: In this phase II trial, we investigated the efficacy of a metronomic temozolomide schedule in the treatment of recurrent malignant gliomas (MGs). METHODS: Eligible patients received daily temozolomide (50 mg/m2) continuously until progression. The primary endpoint was progression-free survival rate at 6 months in the glioblastoma cohort (N = 37). In an exploratory analysis, 10 additional recurrent grade III MG patients were enrolled. Correlative studies included evaluation of 76 frequent mutations in glioblastoma (iPLEX assay, Sequenom) aiming at establishing the frequency of potentially "drugable" mutations in patients entering recurrent MG clinical trials. RESULTS: Among glioblastoma patients, median age was 56 y; median Karnofsky performance score (KPS) was 80; 62% of patients had been treated for ≥2 recurrences, including 49% of patients having failed bevacizumab. Treatment was well tolerated; clinical benefit (complete response + partial response + stable disease) was seen in 10 (36%) patients. Progression-free survival rate at 6 months was 19% and median overall survival was 7 months. Patients with previous bevacizumab exposure survived significantly less than bevacizumab-naive patients (median overall survival: 4.3 mo vs 13 mo; hazard ratio = 3.2; P = .001), but those patients had lower KPS (P = .04) and higher number of recurrences (P < .0001). Mutations were found in 13 of the 38 MGs tested, including mutations of EGFR (N = 10), IDH1 (N = 5), and ERBB2 (N = 1). CONCLUSIONS: In spite of a heavily pretreated population, including nearly half of patients having failed bevacizumab, the primary endpoint was met, suggesting that this regimen deserves further investigation. Results in bevacizumab-naive patients seemed particularly favorable, while results in bevacizumab-failing patients highlight the need to develop further treatment strategies for advanced MG. Clinical identifier NCT00498927 (available at

Full Text

Duke Authors

Cited Authors

  • Omuro, A; Chan, TA; Abrey, LE; Khasraw, M; Reiner, AS; Kaley, TJ; Deangelis, LM; Lassman, AB; Nolan, CP; Gavrilovic, IT; Hormigo, A; Salvant, C; Heguy, A; Kaufman, A; Huse, JT; Panageas, KS; Hottinger, AF; Mellinghoff, I

Published Date

  • February 2013

Published In

Volume / Issue

  • 15 / 2

Start / End Page

  • 242 - 250

PubMed ID

  • 23243055

Pubmed Central ID

  • PMC3548585

Electronic International Standard Serial Number (EISSN)

  • 1523-5866

Digital Object Identifier (DOI)

  • 10.1093/neuonc/nos295


  • eng

Conference Location

  • England