Al's Comment:

 This abstract shows that continuous low dose Temodar might be useful for recurrent GBMs and Anaplastic Astrocytomas, especially if the patient has not yet failed on Avastin.

 An interesting side note is they found a smaller % of patients had mutation in EGFR than previously reported.  Perhaps that means people with these mutations in general do not do well enough to take part in a trial after having a few recurrences.  This has to be taken into consideration for the anti-EGFR trials.. 

Posted on: 12/20/2012

Neuro Oncol. 2012 Dec 14. [Epub ahead of print]
Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma.
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.
Departments of Neurology (A.O., L.E.A., M.K., T.J.K., L.M.D., A.B.L., C.P.N., I.T.G., A.H., C.S., A.F.H., I.M.), Radiation Oncology (T.A.C.), Human Oncology and Pathogenesis Program (T.A.C., A.H., A.K., I.M.), Epidemiology and Biostatistics (A.S.R., K.S.P.), Pathology (J.T.H.), Memorial Sloan-Kettering Cancer Center, New York, New York.
BackgroundIn this phase II trial, we investigated the efficacy of a metronomic temozolomide schedule in the treatment of recurrent malignant gliomas (MGs).MethodsEligible patients received daily temozolomide (50 mg/m(2)) 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
 PMID: 23243055 [PubMed - as supplied by publisher] 


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