Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA–09): a randomised, open-label, phase 3 trial

Herrlinger, Ulrich; Tzaridis, Theophilos; Mack, Frederic; Steinbach, Joachim P.; Schlegel, Uwe; Sabel, Michael; Hau, Peter; Kortmann, Rolf‐Dieter; Krex, Dietmar; Grauer, Oliver; Goldbrunner, Roland; Schnell, Oliver; Bähr, Oliver; Seidel, Clemens; Tabatabai, Ghazaleh; Kowalski, Thomas E.; Ringel, Florian; Schmidt‐Graf, Friederike; Suchorska, Bogdana; Brehmer, Stefanie; Weyerbrock, Astrid; Renovanz, Miriam; Bullinger, Lars; Galldiks, Norbert; Vajkoczy, Peter; Misch, Martin; Vatter, Hartmut; Stuplich, Moritz; Schäfer, Niklas; Kebir, Sied; Weller, Johannes; Schaub, Christina; Stummer, Walter; Tonn, Jörg‐Christian; Simon, Matthias; Keil, Vera C.; Nelles, Michael; Urbach, Horst; Coenen, Martin; Wick, Wolfgang; Weller, Michael; Fimmers, Rolf; Maurizio, Schmid; Hattingen, Elke; Pietsch, Torsten; Coch, Christoph; Glas, Martin

doi:10.1016/s0140-6736(18)31791-4

Cited by 429 publications

(329 citation statements)

References 31 publications

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“…Herrlinger et al investigated the effect of lomustine plus TMZ versus the standard TMZ regimen for newly diagnosed MGMT methylated GBM undergoing radiation in the setting of a randomized phase III trial. 24 The results suggested that lomustine-TMZ chemotherapy may improve OS compared with TMZ standard therapy in patients with a methylated MGMT promoter. However, the hematological side effects were significantly greater in the experimental treatment group.…”

Section: Chemotherapymentioning

confidence: 99%

Neuro-oncology management during the COVID-19 pandemic with a focus on WHO grades III and IV gliomas

et al. 2020

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Abstract Background Because of the increased risk in cancer patients of developing complications caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), physicians have to balance the competing risks of the negative impact of the pandemic and the primary tumor disease. In this consensus statement, an international group of experts present mitigation strategies and treatment guidance for patients suffering from high grade gliomas (HGGs) during the coronavirus disease 2019 (COVID-19) pandemic. Methods Sixteen international experts in the treatment of HGG contributed to this consensus-based practice recommendation, including neuro-oncologists, neurosurgeons, radiation oncologists, and a medical physicist. Generally, treatment of neuro-oncological patients cannot be significantly delayed and initiating therapy should not be outweighed by COVID-19. We present detailed interdisciplinary treatment strategies for molecular subgroups in 2 pandemic scenarios, a scale-up phase and a crisis phase. Conclusion This practice recommendation presents a pragmatic framework and consensus-based mitigation strategies for the treatment of HGG patients during the SARS-CoV-2 pandemic.

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Section: Chemotherapymentioning

confidence: 99%

Neuro-oncology management during the COVID-19 pandemic with a focus on WHO grades III and IV gliomas

et al. 2020

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“…In nearly 100% of cases, this approach fails, resulting in a recurrent tumor with limited therapeutic options. Few therapies are FDA-approved for patients with recurrent GBM, including lomustine, bevacizumab, carmustine wafers, and tumor-treating fields, none of which have demonstrated a marked improvement in overall survival [6][7][8][9] . Multiple other cancers have faced similar obstacles to effective treatment, but this has been recently overcome with the use of immune-modulating therapies, and as a consequence, there is interest in trying to modify the immune system in GBM.…”

Section: Introductionmentioning

confidence: 99%

Metronomic capecitabine as an immune modulator in glioblastoma patients reduces myeloid-derived suppressor cells

Peereboom

Alban

Grabowski

et al. 2019

Preprint

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Background: Myeloid-derived suppressor cells (MDSCs) are elevated in glioblastoma (GBM) patient circulation, present in tumor tissue, and associated with poor prognosis. While low-dose chemotherapy reduces MDSCs in preclinical models, the use of this strategy to reduce MDSCs in GBM patients has yet to be evaluated. Methods:A phase 0/1 dose-escalation clinical trial was conducted in recurrent glioblastoma patients treated 5-7 days prior to surgery with low-dose chemotherapy via capecitabine followed by concomitant low-dose capecitabine and bevacizumab. Clinical outcomes, including progression-free and overall survival, were measured, along with safety and toxicity profiles. Over the treatment time course, circulating MDSC levels were measured by multi-parameter flow cytometry, and tumor tissue immune profiles were assessed via mass cytometry time-of-flight.Results: A total of 11 patients were enrolled across escalating dose cohorts of 150, 300, and 450 mg bid, with a progression-free survival of 5.8 months (range of 1.8-27.8 months) and an overall survival of 11.5 months (range of 3->28.0 months) from trial enrollment. No serious adverse events related to the drug combination were observed. Compared to pre-treatment baseline, circulating MDSCs were found to be higher after surgery in the 150 mg treatment arm and lower in the 300 mg and 450 mg treatment arms. Increased cytotoxic immune infiltration was observed after low-dose capecitabine compared to untreated GBM patients in the 300 mg and 450 mg treatment arms. Conclusions:Low-dose, metronomic capecitabine in combination with bevacizumab is well tolerated in GBM patients and was associated with a reduction in circulating MDSC levels and an increase in cytotoxic immune infiltration into the tumor microenvironment.

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“…New data from Herrlinger et al reinforce a conclusion that chemotherapy is effective in patients with methylated promotor status (8). This study was driven by findings from UKT-03 trial, a small single-arm phase 2 trial (31 patients) that explored combined lomustine/TMZ chemotherapy in patients with newly diagnosed glioblastoma (9,10).…”

Section: A Commentary Onmentioning

confidence: 97%

Commentary: Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA-09): a randomised, open-label, phase 3 trial

2020

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Citation:Das S, Sahgal A and Perry JR (2020) Commentary: Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA-09): a randomised, open-label, phase 3 trial. Front. Oncol. 10:66. Commentary: Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA-09): a randomised, open-label, phase 3 trial

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Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA–09): a randomised, open-label, phase 3 trial

Cited by 429 publications

References 31 publications

Neuro-oncology management during the COVID-19 pandemic with a focus on WHO grades III and IV gliomas

Neuro-oncology management during the COVID-19 pandemic with a focus on WHO grades III and IV gliomas

Metronomic capecitabine as an immune modulator in glioblastoma patients reduces myeloid-derived suppressor cells

Commentary: Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA-09): a randomised, open-label, phase 3 trial

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