Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas

Brada, Michael; Viviers, Louis; Abson, C.; Hines, Frances; Britton, J.; Ashley, S.; Sardell, S.; Traish, D.; Gonsalves, A.; Wilkins, P.; Westbury, Charlotte

doi:10.1093/annonc/mdg371

Cited by 243 publications

(132 citation statements)

References 23 publications

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“…Importantly, we did not only detect frequent 5 0 -CpGisland hypermethylation and reduced expression of PRDX1 in oligodendroglial tumours with 1p and 19q deletions but also provided first evidence that this aberration may be linked to radio-and chemosensitivity of Hs683 glioma cells in vitro. Clinically, it has been well documented in numerous retrospective and prospective studies that 1p/19q deletion in low-grade and anaplastic oligodendroglial tumours predicts response to radiotherapy as well as chemotherapy with TMZ or nitrosourea compounds (Brada et al, 2003;Cairncross et al, 2006;Kouwenhoven et al, 2006;van den Bent, 2006;Wick et al, 2009). The molecular basis for the predictive power of 1p/19q deletion is still unknown.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of PRDX1 by promoter hypermethylation is frequent in 1p/19q-deleted oligodendroglial tumours and increases radio- and chemosensitivity of Hs683 glioma cells in vitro

et al. 2011

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Deletions of chromosomal arms 1p and 19q are frequent in oligodendroglial tumours and linked to radio-and chemotherapy response as well as longer survival. The molecular mechanisms underlying this clinically important association are as yet unknown. Here, we studied the peroxiredoxin 1 (PRDX1) gene at 1p34.1 for promoter methylation and expression in primary gliomas and investigated its role in radio-and chemosensitivity of glioma cells in vitro. In total, we screened primary glioma tissues from 93 patients for methylation of the 5 0 -CpG island of PRDX1 by sodium bisulfite sequencing. PRDX1 mRNA and protein expression levels were determined in subsets of the tumours by quantitative PCR and western blot analysis, respectively. PRDX1 hypermethylation and reduced expression were frequently detected in oligodendroglial tumours and secondary glioblastomas, but not in primary glioblastomas. In oligodendroglial tumours, both PRDX1 hypermethylation and reduced mRNA expression were significantly associated with 1p/19q-deletion. Stable knockdown of PRDX1 by lentiviral transduction of shorthairpin (sh)RNA constructs significantly increased apoptosis and reduced cell viability of Hs683 glioma cells exposed to ionizing irradiation or temozolomide in vitro. Taken together, our findings indicate that epigenetic silencing of PRDX1 is frequent in 1p/19q-deleted oligodendroglial tumours and likely contributes to radioand chemosensitivity of these tumours.

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Section: Discussionmentioning

confidence: 99%

Downregulation of PRDX1 by promoter hypermethylation is frequent in 1p/19q-deleted oligodendroglial tumours and increases radio- and chemosensitivity of Hs683 glioma cells in vitro

et al. 2011

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“…On the basis of excellent tolerance and potential efficacy of temozolomide in lower grade tumours, we evaluated temozolomide as the primary treatment following surgery in patients with grade II glial tumours in a single arm phase II study. The results of the study are the subject of a separate report (Brada et al, 2003).…”

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confidence: 95%

Monitoring temozolomide treatment of low-grade glioma with proton magnetic resonance spectroscopy

et al. 2004

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Assessment of low-grade glioma treatment response remains as much of a challenge as the treatment itself. Proton magnetic resonance spectroscopy ( 1 H-MRS) and imaging were incorporated into a study of patients receiving temozolomide therapy for lowgrade glioma in order to evaluate and monitor tumour metabolite and volume changes during treatment. Patients (n ¼ 12) received oral temozolomide (200 mg m À2 day À1 ) over 5 days on a 28-day cycle for 12 cycles. Response assessment included baseline and three-monthly magnetic resonance imaging studies (pretreatment, 3, 6, 9 and 12 months) assessing the tumour size. Short (TE (echo time) ¼ 20 ms) and long (TE ¼ 135 ms) echo time single voxel spectroscopy was performed in parallel to determine metabolite profiles. The mean tumour volume change at the end of treatment was À33% (s.d. ¼ 20). The dominant metabolite in long echo time spectra was choline. At 12 months, a significant reduction in the mean choline signal was observed compared with the pretreatment (P ¼ 0.035) and 3-month scan (P ¼ 0.021). The reduction in the tumour choline/water signal paralleled tumour volume change and may reflect the therapeutic effect of temozolomide.

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“…For a long time, radiotherapy has represented the mainstay of treatment for this type of lesions, but radiation-induced toxicity still has to be carefully considered during decision-making. 12) Although no consensus on the routine use of chemotherapy in treating LGG, and especially astrocytomas, has been reached yet, its efficacy has been demonstrated in terms of clinical and radiological response either as initial treatment [2][3][4]8,10,13,15,24,27) or as salvage therapy after surgery and radiotherapy. 17,18,22,23,26,27) Complete neuroradiological disappearance of a tumor is infrequent, so good response is defined as volumetric regression or stabilization over time.…”

Section: Discussionmentioning

confidence: 99%

“…In this group of patients, once biopsy has been performed, radiotherapy or chemotherapy is then administered. Chemotherapy can reduce volume and infiltration of LGGs, [2][3][4]8,10,13,17,18,22,24,26,27) and can permit total resection of an initially diffuse tumor. 6) We report a case of a patient in which neoadjuvant chemotherapy allowed surgical treatment of a large infiltrating LGG.…”

Section: Introductionmentioning

confidence: 99%

Preoperative Chemotherapy for Infiltrative Low-Grade Oligoastrocytoma: a Useful Strategy to Maximize Surgical Resection -Case Report-

Spena

Garbossa

Barletta

et al. 2010

Neurol. Med. Chir.(Tokyo)

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A 38-year-old woman presented with a large infiltrative left frontal low-grade glioma manifesting as partial seizures of the left arm and lower limb. First line chemotherapy with temozolomide reduced infiltration and volume, allowing subtotal surgical resection. The patient suffered postoperative supplementary motor area syndrome with right hemiparesis and mutism that resolved completely after approximately one month. She was able to return to her full-time job after 4 months. The residual tumor was stable, and the frequency of seizures had lessened dramatically at the last follow-up examination at 18 months. The present case demonstrates that this new therapeutic approach of chemotherapy followed by surgery can offer safer and more radical surgical resection, improving the quality of life of the patient.

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Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas

Cited by 243 publications

References 23 publications

Downregulation of PRDX1 by promoter hypermethylation is frequent in 1p/19q-deleted oligodendroglial tumours and increases radio- and chemosensitivity of Hs683 glioma cells in vitro

Downregulation of PRDX1 by promoter hypermethylation is frequent in 1p/19q-deleted oligodendroglial tumours and increases radio- and chemosensitivity of Hs683 glioma cells in vitro

Monitoring temozolomide treatment of low-grade glioma with proton magnetic resonance spectroscopy

Preoperative Chemotherapy for Infiltrative Low-Grade Oligoastrocytoma: a Useful Strategy to Maximize Surgical Resection -Case Report-

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