scholarly journals Comparing Outcomes of Patients Treated With Radiation Therapy With or Without Concurrent and Adjuvant Temozolomide After Surgical Resection for Newly Diagnosed WHO Grade 3 Anaplastic Astrocytoma

2017 ◽  
Vol 99 (2) ◽  
pp. E62
Author(s):  
A. Ali ◽  
S. Garg ◽  
L. Kim ◽  
J. Glass ◽  
B.E. Leiby ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Surgical Resection ◽  
Anaplastic Astrocytoma ◽  
Newly Diagnosed ◽  
Who Grade ◽  
Adjuvant Temozolomide ◽  
Grade 3

scholarly journals SYST-08. A phase II trial of concurrent Sunitinib, Temozolomide and Radiation Therapy followed by adjuvant Temozolomide for newly diagnosed Glioblastoma patients with an unmethylated MGMT gene promoter (A01-M121-11A, McG1132)

2021 ◽  
Vol 3 (Supplement_4) ◽  
pp. iv10-iv10
Author(s):  
Mame Daro Faye ◽  
Siham Sabri ◽  
Paula De Robles ◽  
Raman Agnihotram ◽  
Alexander Torres-Vasquez ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Standard Of Care ◽  
Treatment Modalities ◽  
Newly Diagnosed ◽  
Current Standard ◽  
Who Grade ◽  
Adjuvant Temozolomide ◽  
Mgmt Promoter ◽  
Grade 3

Abstract INTRODUCTION Despite advances in treatment modalities, the overall prognosis of GBM remains dismal, particularly for patients with unmethylated MGMT promoter. Thus, alternative treatment strategies are warranted. Our group has previously shown that addition of Sunitinib (SU11248) to standard therapy significantly improved the response of unmethylated MGMT cells through decreased angiogenicity and tumorigenicity. In this phase II trial, we tested for the first time the combination of Sunitinib with RT and Temozolomide in newly diagnosed MGMT unmethylated GBM patients. METHODS Patients with histologically confirmed WHO Grade IV GBM and MS-PCR confirmed unmethylated MGMT promoter, age 18-70, KPS ≥70, life expectancy ≥6 months were eligible. 41 patients treated between 2012 and 2017 were screened, 37 of which were eligible. Patients received 12.5 mg of daily Sunitinib for 7 days, followed by concurrent RT, Temozolomide and 12.5 mg Sunitinib for 6 weeks, then adjuvant Temozolomide x6 cycles. RT and Temozolomide doses were as per standard of care. Primary objective was PFS as assessed by RANO criteria, secondary objectives were OS and safety. RESULTS Median follow-up time was 15 months. Median PFS was 7 months (95%CI, 6.7-7.2) and 6-month PFS was 59.3%. Median OS was 13 months (95%CI, 12.62-13.37) and 2-year OS was 17.8%. Two patients had OS >50 months, with one surviving 71 months. Having received >3 cycles of adjuvant Temozolomide, surgery at progression or age ≤65 significantly predicted for better OS, with hazard ratios of 0.184 (p=0.001), 0.402 (p=0.026) and 10.017 (for age >65, p=0.002) respectively. Grade ≥3 thrombocytopenia occurred in 18.9% of patients, grade ≥3 neutropenia in 10.8% and grade ≥3 thromboembolic events in 13.5%. There were no grade 5 evens. CONCLUSION Addition of Sunitinib to RT and Temozolomide was well tolerated and survival outcomes compared favorably to the current standard of care for GBM patients with unmethylated MGMT promoter status.

scholarly journals INNV-07. THE KOREAN SOCIETY FOR NEURO-ONCOLOGY (KSNO) GUIDELINE FOR GLIOMAS: VERSION 2019.01

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi131-vi132
Author(s):  
Young Zoon Kim ◽  
Chae-Yong Kim ◽  
Do Hoon Lim ◽  
Dong-Sup Chung
Keyword(s):  
Anaplastic Astrocytoma ◽  
Poor Performance ◽  
Diffuse Astrocytoma ◽  
Molecular Feature ◽  
Who Grade ◽  
Korean Society ◽  
Brain Radiotherapy ◽  
Adjuvant Temozolomide ◽  
Radiotherapy Alone ◽  
Temozolomide Chemotherapy

Abstract BACKGROUND There was no practical guideline for the management of patients with central nervous system (CNS) tumor in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, started to prepare a guideline for CNS tumors from February 2018. METHODS The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. RESULTS First, for the glioblastoma as WHO Grade IV Gliomas, the maximal safe resection if feasible is recommended. Patients aged ≤ 70 years with good performance should be treated by concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide chemotherapy (Stupp’s protocol) or standard brain radiotherapy alone. However, those with poor performance should be treated by hypofractionated brain radiotherapy (preferred) ± concurrent or adjuvant temozolomide or temozolomide alone (Level III) or supportive treatment. Second, for the WHO Grade III Gliomas, patients with anaplastic astrocytoma, IDH-mutant should be treated by standard brain radiotherapy followed by adjuvant temozolomide chemotherapy, or Stupp’s protocol, or standard brain radiotherapy with neoadjuvant or adjuvant PCV chemotherapy, or Standard brain radiotherapy alone (Level III). However, those anaplastic astrocytoma, IDH-wildtype should be treated by the protocol for glioblastoma. Third, for the WHO Grade II Gliomas, patients with diffuse astrocytoma, IDH-wildtype without molecular feature of glioblastoma should be treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy (Level III), or standard brain radiotherapy alone, or observation. And patients with diffuse astrocytoma IDH-mutant and oligodendroglioma (IDH-mutant and 1p/19q codeletion) should be treated according to the risk factors. CONCLUSION The recent KSNO’s guideline recommends that glioma should be treated according to the molecular as well as histological features. However, the practice can be limited by the National Insurance for Health in Korea.

Promising Survival for Patients With Newly Diagnosed Glioblastoma Multiforme Treated With Concomitant Radiation Plus Temozolomide Followed by Adjuvant Temozolomide

2002 ◽  
Vol 20 (5) ◽  
pp. 1375-1382 ◽  
Author(s):  
Roger Stupp ◽  
Pierre-Yves Dietrich ◽  
Sandrine Ostermann Kraljevic ◽  
Alessia Pica ◽  
Ivan Maillard ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase Ii ◽  
Pneumocystis Carinii ◽  
Survival Rates ◽  
Concomitant Treatment ◽  
Newly Diagnosed ◽  
Open Label ◽  
Fractionated Radiotherapy ◽  
Adjuvant Temozolomide ◽  
Grade 3

PURPOSE: Temozolomide is a novel oral alkylating agent with demonstrated efficacy as second-line therapy for patients with recurrent anaplastic astrocytoma and glioblastoma multiforme (GBM). This phase II study was performed to determine the safety, tolerability, and efficacy of concomitant radiation plus temozolomide therapy followed by adjuvant temozolomide therapy in patients with newly diagnosed GBM. PATIENTS AND METHODS: Sixty-four patients were enrolled onto this open-label, phase II trial. Temozolomide (75 mg/m2/d × 7 d/wk for 6 weeks) was administered orally concomitant with fractionated radiotherapy (60 Gy total dose: 2 Gy × 5 d/wk for 6 weeks) followed by temozolomide monotherapy (200 mg/m2/d × 5 days, every 28 days for six cycles). The primary end points were safety and tolerability, and the secondary end point was overall survival. RESULTS: Concomitant radiation plus temozolomide therapy was safe and well tolerated. Nonhematologic toxicities were rare and mild to moderate in severity. During the concomitant treatment phase, grade 3 or 4 neutropenia, thrombocytopenia, or both were observed in 6% of patients, including two severe infections with Pneumocystis carinii. During adjuvant temozolomide, 2% and 6% of cycles were associated with grade 3 and 4 neutropenia or thrombocytopenia, respectively. Median survival was 16 months, and the 1- and 2-year survival rates were 58% and 31%, respectively. Patients younger than 50 years old and patients who underwent debulking surgery had the best survival outcome. CONCLUSION: Continuous daily temozolomide and concomitant radiation is safe. This regimen of concomitant chemoradiotherapy followed by adjuvant chemotherapy may prolong the survival of patients with glioblastoma. Further investigation is warranted, and a randomized trial is ongoing.

BMX-HGG: Phase II trial of newly diagnosed high-grade glioma treated with concurrent radiation therapy, temozolomide, and BMX-001.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS2577-TPS2577
Author(s):  
Katherine B. Peters ◽  
Adam Louis Cohen ◽  
Nicholas A. Butowski ◽  
John L. Villano ◽  
Pierre Giglio ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
White Matter ◽  
Cancer Therapy ◽  
Phase Ii ◽  
Functional Assessment ◽  
Phase Ii Study ◽  
High Grade Glioma ◽  
High Grade ◽  
Newly Diagnosed ◽  
Who Grade

TPS2577 Background: Patients diagnosed with malignant high-grade gliomas (WHO grade III-IV) experience significant morbidity and mortality associated with these cancers. While the mainstay of therapy for patients with newly diagnosed high-grade glioma is surgery followed by concurrent chemotherapy and radiation therapy (RT), the outcomes remain very poor. BMX-001 (MnTnBuOE-2-PyP5+) is a metalloporphyrin with differential action in response to radiation therapy and chemotherapy-induced oxidative stress. Early preclinical studies demonstrated BMX-001’s ability to act as a radioprotectant to healthy tissue such as a central nervous white matter and as a radiosensitizer to cancer cells, in particular, human glioblastoma xenografts. We evaluated the safety of BMX-001 in combination with concurrent RT and temozolomide (TMZ) in a phase I study of newly diagnosed high-grade glioma patients, and we found that BMX-001 is safe and well-tolerated in this population. The maximum tolerated dose of BMX-001 during concurrent RT and TMZ was determined to be 28 mg delivered subcutaneously (SC) followed by 16 biweekly SC doses at 14 mg (Peters et al., Neuro-Oncology 2018). Methods: For this multi-site, open-label, phase II study (NCT02655601), we will randomize approximately 160 patients 1:1 to concurrent RT and TMZ with BMX-001 versus concurrent RT and TMZ alone. Key eligibility criteria include newly diagnosed histologically confirmed high-grade glioma (WHO III-IV), 18 ≥ years, and Karnofsky performance status ≥ 70%. The primary endpoint is overall survival. Secondary endpoints include cognitive performance as assessed by standardized cognitive testing, bone marrow protection, safety and tolerability, progression-free survival, overall tumor response rate, and plasma pharmacokinetics. Exploratory endpoints are health-related quality of life (as assessed by Functional Assessment of Cancer Therapy–Brain, Functional Assessment of Cancer Therapy-Cognition, and Functional Assessment of Chronic Illness Therapy-Fatigue), qualitative hair loss, and white matter integrity (as measured by MRI diffusion tensor/susceptibility imaging). Since November 2018, this phase II study has enrolled 64 of 160 high-grade glioma patients at six sites with future sites planned to be implemented. Clinical trial information: NCT02655601 .

scholarly journals Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline

2021 ◽  
Author(s):  
Nimish A. Mohile ◽  
Hans Messersmith ◽  
Na Tosha Gatson ◽  
Andreas F. Hottinger ◽  
Andrew Lassman ◽  
...  
Keyword(s):  
Performance Status ◽  
Treatment Options ◽  
Poor Performance ◽  
Best Supportive Care ◽  
Poor Performance Status ◽  
Newly Diagnosed ◽  
Who Grade ◽  
Oligodendroglial Tumors ◽  
Mgmt Promoter ◽  
Grade 3

PURPOSE To provide guidance to clinicians regarding therapy for diffuse astrocytic and oligodendroglial tumors in adults. METHODS ASCO and the Society for Neuro-Oncology convened an Expert Panel and conducted a systematic review of the literature. RESULTS Fifty-nine randomized trials focusing on therapeutic management were identified. RECOMMENDATIONS Adults with newly diagnosed oligodendroglioma, isocitrate dehydrogenase (IDH)–mutant, 1p19q codeleted CNS WHO grade 2 and 3 should be offered radiation therapy (RT) and procarbazine, lomustine, and vincristine (PCV). Temozolomide (TMZ) is a reasonable alternative for patients who may not tolerate PCV, but no high-level evidence supports upfront TMZ in this setting. People with newly diagnosed astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 2 should be offered RT with adjuvant chemotherapy (TMZ or PCV). People with astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 should be offered RT and adjuvant TMZ. People with astrocytoma, IDH-mutant, CNS WHO grade 4 may follow recommendations for either astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 or glioblastoma, IDH-wildtype, CNS WHO grade 4. Concurrent TMZ and RT should be offered to patients with newly diagnosed glioblastoma, IDH-wildtype, CNS WHO grade 4 followed by 6 months of adjuvant TMZ. Alternating electric field therapy, approved by the US Food and Drug Administration, should be considered for these patients. Bevacizumab is not recommended. In situations in which the benefits of 6-week RT plus TMZ may not outweigh the harms, hypofractionated RT plus TMZ is reasonable. In patients age ≥ 60 to ≥ 70 years, with poor performance status or for whom toxicity or prognosis are concerns, best supportive care alone, RT alone (for MGMT promoter unmethylated tumors), or TMZ alone (for MGMT promoter methylated tumors) are reasonable treatment options. Additional information is available at www.asco.org/neurooncology-guidelines .

Ultrafractionated radiation therapy (3x per day) for glioblastoma: Preliminary results of a phase II study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1570-1570
Author(s):  
P. D. Beauchesne ◽  
L. Taillandier ◽  
V. Bernier ◽  
M. Djabri ◽  
X. Michel ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Phase Ii ◽  
High Efficiency ◽  
Phase Ii Study ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Progression Free Survival ◽  
Who Grade ◽  
Primary Endpoints ◽  
Grade 3

1570 Background: Ultrafractionation radiation therapy consists in irradiating cells or tumors several times daily, delivering low doses at which hyperradiosensitivity occur. We recently reported the high efficiency of ultrafractionation radiotherapy in glioma cell lines and xenografts, and are now conducting a phase II clinical trial to determine the effect of an ultrafractionation regimen for glioblastoma patients. Methods: A prospective, multicenter, phase II study has opened for accrual in September 2003. Patients over 18 years of age who are able to give informed consent and have histologically proven, newly diagnosed and unresectable, supratentorial glioblastoma (WHO grade IV) are eligible. Three doses of 0.75 Gy spaced by at least four hours are delivered daily, five days a week for six consecutive weeks for a total of 67.5 Gy. Conformal irradiation includes the tumor bulk including a margin of 2.5 cm. Tolerance and toxicity are the primary endpoints; survival and progression-free survival are secondary endpoints. Results: To date 25 patients have been enrolled in this study, 19 currently evalualbe: 11 men and 8 women, median age 58 (range 37 to 76), median Karnofsky performance status (80 range from 70 to 100). The median time between histological diagnosis and the start of treatment is 7 weeks. The ultrafractionated radiation therapy has been well tolerated; no acute grade 3 and/or 4 CNS toxicity has been observed. Minor responses at the end of irradiation were seen in 5 patients. Median survival from initial diagnosis was 13.5 months, nine patients remain alive. Conclusions: Ultrafractionated radiation therapy is safe and well tolerated. No acute CNS toxicitiy has been observed. Overall survival of over 13 months for patients without prior debulking surgery compares favorably with other reports. Updated definitive results will be presented. No significant financial relationships to disclose.

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