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

Omuro, Antonio, Chan, Timothy A., Abrey, Lauren E., Khasraw, Mustafa, Reiner, Anne S., Kaley, Thomas J., DeAngelis, Lisa M., Lassman, Andrew B., Nolan, Craig P., Gavrilovic, Igor T., Hormigo, Adilia, Salvant, Cynthia, Heguy, Adriana, Kaufman, Andrew, Huse, Jason T., Panageas, Katherine S., Hottinger, Andreas F. and Mellinghoff, Ingo 2013, Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma, Neuro-Oncology, vol. 15, no. 2, pp. 242-250, doi: 10.1093/neuonc/nos295.

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Title Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma
Author(s) Omuro, Antonio
Chan, Timothy A.
Abrey, Lauren E.
Khasraw, MustafaORCID iD for Khasraw, Mustafa
Reiner, Anne S.
Kaley, Thomas J.
DeAngelis, Lisa M.
Lassman, Andrew B.
Nolan, Craig P.
Gavrilovic, Igor T.
Hormigo, Adilia
Salvant, Cynthia
Heguy, Adriana
Kaufman, Andrew
Huse, Jason T.
Panageas, Katherine S.
Hottinger, Andreas F.
Mellinghoff, Ingo
Journal name Neuro-Oncology
Volume number 15
Issue number 2
Start page 242
End page 250
Total pages 9
Publisher Oxford University Press
Place of publication Cary, N. C.
Publication date 2013
ISSN 1522-8517
Keyword(s) bevacizumab
malignant glioma
metronomic chemotherapy
Summary 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.
Language eng
DOI 10.1093/neuonc/nos295
Field of Research 111203 Cancer Genetics
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
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Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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Created: Thu, 21 Feb 2013, 12:55:22 EST by Jane Moschetti

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