Combined temozolomide and radiation as an initial treatment for anaplastic glioma

Tham, Chee Kian; See, Siew Ju; Tan, Sze Huey; Lim, Keith; Ng, Wai Hoe; Thomas, John C.; Chong, Dawn Q.; Chua, Eu Tiong

doi:10.1111/ajco.12038

Cited by 8 publications

(6 citation statements)

References 21 publications

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“…These tumors used to be included in trials together with glioblastoma as high-grade gliomas, and there have been few studies focused only on grade 3 glioma. Postoperative radiotherapy in combination with chemotherapy has improved the prognosis of highgrade glioma, with the median OS reported as two years for AA and four years for AO [6], although the prognosis is highly variable depending on factors such as the extent of resection and molecular markers [7][8][9]. The prognosis in our study was comparable to that in previous studies.…”

Section: Discussionsupporting

confidence: 78%

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Radiation Therapy for Grade 3 Gliomas: Correlation of MRI Findings With Prognosis

Mizumoto¹,

Liang²,

Oshiro³

et al. 2021

Cureus

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Background and objectivePostoperative radiotherapy is usually indicated for both grade 3 glioma and grade 4 glioblastoma. However, the treatment results and tumor features of grade 3 glioma clearly differ from those of glioblastoma. There is limited information on outcomes and tumor progression for grade 3 glioma. In this study, we evaluate the result of postoperative radiotherapy for grade 3 glioma and focus on the correlation of MRI findings with prognosis. MethodsIn this study, 99 of 110 patients with grade 3 glioma who received postoperative radiotherapy and were followed up for more than one year were retrospectively analyzed. The total irradiation dose was 60.0 Gy in 30 fractions, and daily temozolomide or two cycles of nimustine (ACNU) was concurrently administered during radiotherapy. The median follow-up period was 46 months (range: 2-151 months). ResultsIn multivariate analysis, pathology [anaplastic oligodendroglioma (AO) vs. anaplastic astrocytoma (AA)], the status of surgical resection (biopsy vs. partial resection or more), and contrast enhancement (enhanced by MRI image or not) were significant factors for overall survival (OS). The five-year OS for AO vs. AA cases were 76.8% vs. 46.1%, total to partial resection vs. biopsy cases were 72.7% vs. 21.0%, and non-enhanced vs. enhanced cases were 82.5% vs. 45.6%, respectively. In multivariate analysis, the status of surgical resection and longer extension of preoperative edema (PE) were significant factors for progression-free survival (PFS). The five-year PFS for the total to partial resection vs. biopsy cases were 52.9% vs. 10.7%, and non-extensive PE vs. extensive PE (EPE) cases were 62.2% vs. 19.1%, respectively. ConclusionOur results suggest that a contrast-enhanced tumor on MRI and a longer PE may also be significantly associated with OS and PFS among grade 3 glioma patients.

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Section: Discussionsupporting

confidence: 78%

“…Postoperative radiotherapy is usually indicated for both grade 3 glioma and grade 4 glioblastoma. However, the treatment results and tumor features of grade 3 glioma clearly differ from those of glioblastoma, but there is scarce data on outcomes and tumor progression for grade 3 glioma [1][2][3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Radiation Therapy for Grade 3 Gliomas: Correlation of MRI Findings With Prognosis

Mizumoto¹,

Liang²,

Oshiro³

et al. 2021

Cureus

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“…Stupp and colleagues have reported that survival of patients who received the combination therapy of TMZ and radiation exceeded that of radiation alone [ 32 ]. Unfortunately, there is no significant benefit of using similar approach in our patient cohort [ 33 ]. This may be due to the small number of patient cohort, or perhaps, the genetic aberrations of Asian glioma patients differ from those of Caucasian glioma patients.…”

Section: Discussionmentioning

confidence: 99%

Combined treatment of Nimotuzumab and rapamycin is effective against temozolomide-resistant human gliomas regardless of the EGFR mutation status

Chong

Toh

et al. 2015

BMC Cancer

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BackgroundThe treatment of glioblastoma multiforme (GBM) is an unmet clinical need. The 5-year survival rate of patients with GBM is less than 3%. Temozolomide (TMZ) remains the standard first-line treatment regimen for gliomas despite the fact that more than 90% of recurrent gliomas do not respond to TMZ after repeated exposure. We have also independently shown that many of the Asian-derived glioma cell lines and primary cells derived from Singaporean high-grade glioma patients are indeed resistant to TMZ. This issue highlights the need to develop new effective anti-cancer treatment strategies. In a recent study, wild-type epidermal growth factor receptor (wtEGFR) has been shown to phosphorylate a truncated EGFR (known as EGFRvIII), leading to the phosphorylation of STAT proteins and progression in gliomagenesis. Despite the fact that combination of EGFR targeting drugs and rapamycin has been used before, the effect of mono-treatment of Nimotuzumab, rapamycin and combination therapy in human glioma expressing different types of EGFR is not well-studied. Herein, we evaluated the efficacy of dual blockage using monoclonal antibody against EGFR (Nimotuzumab) and an mTOR inhibitor (rapamycin) in Caucasian patient-derived human glioma cell lines, Asian patient-derived human glioma cell lines, primary glioma cells derived from the Mayo GBM xenografts, and primary short-term glioma culture derived from high-grade glioma patients.MethodsThe combination effect of Nimotuzumab and rapamycin was examined in a series of primary human glioma cell lines and glioma cell lines. The cell viability was compared to TMZ treatment alone. Endogenous expressions of EGFR in various GBM cells were determined by western blotting.ResultsThe results showed that combination of Nimotuzumab with rapamycin significantly enhanced the therapeutic efficacy of human glioma cells compared to single treatment. More importantly, many of the Asian patient-derived glioma cell lines and primary cells derived from Singaporean high-grade gliomas, which showed resistance to TMZ, were susceptible to the combined treatments.ConclusionsIn conclusion, our results strongly suggest that combination usage of Nimotuzumab and rapamycin exert higher cytotoxic activities than TMZ. Our data suggest that this combination may provide an alternative treatment for TMZ-resistant gliomas regardless of the EGFR status.

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“…Until now, there have been limited trials examining the efficacy and safety of temozolomide for patients with WHO grade III gliomas based on prospective molecular stratification. Furthermore, for patients with WHO grade III gliomas, the addition of temozolomide to radiotherapy, rather than PCV, is unusual [24]. Available data demonstrate with fair clarity that temozolomide is less toxic, easier to prescribe and less complicated for patients [25].…”

Section: Discussionmentioning

confidence: 99%

Concurrent and Adjuvant Temozolomide for Newly Diagnosed Grade III Gliomas without 1p/19q Co-deletion: A Randomized, Open-Label, Phase 2 Study (KNOG-1101 Study)

et al. 2020

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PurposeWe investigated the efficacy of temozolomide during and after radiotherapy in Korean adults with anaplastic gliomas without 1p/19q co-deletion.Materials and MethodsThis was a randomized, open-label, phase 2 study and notably the first multicenter trial for Korean grade III glioma patients. Eligible patients were aged 18 years or older and had newly diagnosed non-co-deleted anaplastic glioma with an Eastern Cooperative Oncology Group performance status of 0-2. Patients were randomized 1:1 to receive radiotherapy alone (60 Gy in 30 fractions of 2 Gy) (control group, n=44) or to receive radiotherapy with concurrent temozolomide (75 mg/m2/day) followed by adjuvant temozolomide (150-200 mg/m2/day for 5 days during six 28-day cycles) (treatment group, n=40). The primary end-point was 2-year progression-free survival (PFS). Seventy patients (83.3%) were available for the analysis of the isocitrate dehydrogenase 1 gene (IDH1) mutation status.ResultsThe two-year PFS was 42.2% in the treatment group and 37.2% in the control group. Overall survival (OS) did not reach to significant difference between the groups. In multivariable analysis, age was a significant risk factor for PFS (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.04 to 4.16). The IDH1 mutation was the only significant prognostic factor for PFS (HR, 0.28; 95% CI, 0.13 to 0.59) and OS (HR, 0.19; 95% CI, 0.07 to 0.50). Adverse events over grade 3 were seen in 16 patients (40.0%) in the treatment group and were reversible.ConclusionConcurrent and adjuvant temozolomide in Korean adults with newly diagnosed non-co- deleted anaplastic gliomas showed improved 2-year PFS. The survival benefit of this regimen needs further analysis with long-term follow-up at least more than 10 years.

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Combined temozolomide and radiation as an initial treatment for anaplastic glioma

Abstract: No significant benefit of combined TMZ with RT compared to RT alone was observed as the initial treatment of anaplastic glioma. Prospective randomized trials are needed to evaluate the optimal treatment for this disease.

Cited by 8 publications

References 21 publications

Radiation Therapy for Grade 3 Gliomas: Correlation of MRI Findings With Prognosis

Radiation Therapy for Grade 3 Gliomas: Correlation of MRI Findings With Prognosis

Combined treatment of Nimotuzumab and rapamycin is effective against temozolomide-resistant human gliomas regardless of the EGFR mutation status

Concurrent and Adjuvant Temozolomide for Newly Diagnosed Grade III Gliomas without 1p/19q Co-deletion: A Randomized, Open-Label, Phase 2 Study (KNOG-1101 Study)

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