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.

scholarly journals CTNI-43. ANLOTINIB COMBINED WITH STUPP REGIMEN IN TREATING PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME: A PHASE II PILOT STUDY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii52-ii52
Author(s):  
Shuzhen Lai ◽  
Yuanyuan Chen
Keyword(s):  
Pilot Study ◽  
Glioblastoma Multiforme ◽  
Adjuvant Therapy ◽  
Disease Progression ◽  
Phase Ii ◽  
Signal Pathways ◽  
Severe Toxicity ◽  
Newly Diagnosed ◽  
Newly Diagnosed Glioblastoma ◽  
Grade 3

Abstract PURPOSE Anlotinib, an orally multi-target tyrosine kinase inhibitor, inhibits tumor angiogenic and proliferative signal pathways. We performed a phase II trial of anlotinib in combination with the STUPP regimen in patients with newly diagnosed glioblastoma multiforme（GBM）to determine whether the combination therapy would safely improve outcomes in this group of patients. An initial pilot study assessed interim safety and tolerability. METHODS AND MATERIALS Ten newly diagnosed GBM patients were included in this study. All patients received standard radiation of 60 Gy in 30 fractions starting within 4–6 weeks after surgery with concurrent TMZ (daily, 75 mg/m2) and anlotinib (8mg per day, from day 1 to 14, every 3 weeks). After a 4-week break, adjuvant therapy including 6 cycles of TMZ (150–200 mg/m², from day 1 to 5, every 4 weeks) and 8 cycles of anlotinib (8mg per day, from day 1 to 14, every 3 weeks) was given. For patients completing adjuvant therapy, anlotinib alone (8mg per day, from day 1 to 14, every 3 weeks) was administrated until disease progression. RESULTS All patients completed concurrent chemo-radiotherapy without interruption. One patient developed grade 3 weight loss at 56th week and grade 3 presumed radiation-induced cognitive disturbance at 60th week. Fatigue and hypertension were frequently observed during treatment, which potentially be related to the treatment. No severe toxicity was observed in other patients. Up to this writing, none of these patients developed disease progression. CONCLUSION Anlotinib combined with the STUPP regimen is a potential choice for newly diagnosed GBM patients. It is well tolerated and the toxicity is manageable. It’s acceptable to continue enrolling of this Phase II study.

scholarly journals Phase II Study of Erlotinib Plus Temozolomide During and After Radiation Therapy in Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma

2009 ◽  
Vol 27 (4) ◽  
pp. 579-584 ◽  
Author(s):  
Michael D. Prados ◽  
Susan M. Chang ◽  
Nicholas Butowski ◽  
Rebecca DeBoer ◽  
Rupa Parvataneni ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Molecular Markers ◽  
Glioblastoma Multiforme ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Methylation Status ◽  
Strong Positive Correlation ◽  
Newly Diagnosed ◽  
Phase Ii Trials ◽  
Open Label

Purpose This open-label, prospective, single-arm, phase II study combined erlotinib with radiation therapy (XRT) and temozolomide to treat glioblastoma multiforme (GBM) and gliosarcoma. The objectives were to determine efficacy of this treatment as measured by survival and to explore the relationship between molecular markers and treatment response. Patients and Methods Sixty-five eligible adults with newly diagnosed GBM or gliosarcoma were enrolled. We intended to treat patients not currently treated with enzyme-inducing antiepileptic drugs (EIAEDs) with 100 mg/d of erlotinib during XRT and 150 mg/d after XRT. Patients receiving EIAEDs were to receive 200 mg/d of erlotinib during XRT and 300 mg/d after XRT. After XRT, the erlotinib dose was escalated until patients developed tolerable grade 2 rash or until the maximum allowed dose was reached. All patients received temozolomide during and after XRT. Molecular markers of epidermal growth factor receptor (EGFR), EGFRvIII, phosphatase and tensin homolog (PTEN), and methylation status of the promotor region of the MGMT gene were analyzed from tumor tissue. Survival was compared with outcomes from two historical phase II trials. Results Median survival was 19.3 months in the current study and 14.1 months in the combined historical control studies, with a hazard ratio for survival (treated/control) of 0.64 (95% CI, 0.45 to 0.91). Treatment was well tolerated. There was a strong positive correlation between MGMT promotor methylation and survival, as well as an association between MGMT promotor-methylated tumors and PTEN positivity shown by immunohistochemistry with improved survival. Conclusion Patients treated with the combination of erlotinib and temozolomide during and following radiotherapy had better survival than historical controls. Additional studies are warranted.

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 ACTR-03. FINAL RESULTS OF A PHASE II STUDY OF HYPOFRACTIONATED RADIOTHERAPY WITH CONCURRENT AND ADJUVANT TEMOZOLOMIDE IN PATIENTS OVER 70 YEARS OLD WITH NEWLY DIAGNOSED GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi12-vi12
Author(s):  
Mehran Yusuf ◽  
Jeremy Gaskins ◽  
Shiao Woo ◽  
Eric Burton
Keyword(s):  
Phase Ii ◽  
Methylation Status ◽  
Progression Free Survival ◽  
Hypofractionated Radiotherapy ◽  
Newly Diagnosed ◽  
Linear Effect ◽  
Adjuvant Temozolomide ◽  
Kaplan Meier ◽  
Newly Diagnosed Glioblastoma ◽  
Grade 3

Abstract BACKGROUND We sought to determine the efficacy and tolerability of hypofractionated radiotherapy (HFRT), 34Gy given over two weeks with concurrent and adjuvant temozolomide, in patients over 70 years old with newly diagnosed GBM. METHODS Patients ≥ 70 years of age with newly diagnosed GBM received HFRT to a dose of 34 Gy in 10 fractions over 2 weeks, delivered with concurrent and adjuvant TMZ. Quality of life (QOL) data using the validated functional assessment of cancer therapy-brain (FACT-BR) questionnaire was collected. Kaplan-Meier methods and log-rank tests were used for survival analyses. A random intercepts growth model with baseline and linear effect in time terms was used to assess QOL with relation to protocol treatment. RESULTS Eleven patients were enrolled from 12/1/2015 to 2/5/2018. Median age and KPS of the cohort was 74 years (range 70 -81) and 80 (range 60–100). Eight patients have died. Median follow-up of the cohort was 13.8 months (range 3 – 26 months). The median progression free survival (PFS) was 6.0 months (CI 4.7 months -not achieved (NA) and the median overall survival (OS) was 24.5 months (CI 10.2 months –NA). MGMT methylation status was significantly associated with both PFS (p =0.02) and OS (p =0.02). All patients completed HFRT with no patients developing ≥ grade 3 adverse treatment events. QOL did not significantly worsen over time with therapy (p =0.75). CONCLUSIONS This completed phase II trial suggest a HFRT schedule of 34Gy delivered over 2 weeks with concomitant and adjuvant TMZ is well tolerated in elderly GBM patients without compromising clinical outcomes. This result compares favorably to the longer HFRT regimen of 40Gy over 3 weeks. ClinicalTrials.gov identifier: NCT01985087

Enzastaurin (ENZ) before and concomitant with radiation therapy (RTX), followed by ENZ maintenance therapy in patients with newly diagnosed glioblastoma (GBM) without hypermethylation of the O6-methylguanyl DNA-methyltransferase (MGMT) promoter: A multicenter, open-label, uncontrolled phase II study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13038-e13038
Author(s):  
W. Wick Wolfgang ◽  
S. E. Combs ◽  
M. Platten ◽  
M. Weller ◽  
U. Ohnmacht ◽  
...  
Keyword(s):  
Phase Ii ◽  
Dna Methyltransferase ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Unmet Need ◽  
Newly Diagnosed ◽  
Open Label ◽  
Split Dose ◽  
Mgmt Promoter ◽  
Grade 3

e13038 Background: There is an unmet need to improve efficacy outcome for GBM patients without hypermethylation of the MGMT promoter. Preclinical data indicated a potential benefit of ENZ, an oral serine/threonine kinase inhibitor, together with RTX (Tabatabai et al; Ann Neurol 61: 2007). In a run-in phase of this phase II study the feasibility of once or twice daily ENZ dosing was evaluated. The split dose results in higher exposure. The results of the run-in phase are presented. Methods: Patients (pts) with newly diagnosed supratentorial GBM were entered. The first regimen administered once daily ENZ (500 mg QD) before and concomitant with standard radiotherapy at a dose of 60 Gy (2 Gy, 5 days a week). As no dose-limiting toxicities occurred in the first 3 pts, another 6 pts were enrolled into the second regimen, twice daily ENZ (250 mg BID) with RTX. ENZ is given until progression afterward. Results: Between 10/07 and 07/08 a total of 9 pts were enrolled. Mean treatment duration was 9.3 weeks for ENZ, and 6.3 weeks for RTX. No drug-related grade 3/4 toxicity was reported. The only laboratory toxicity CTC grade 3 (low potassium) and 1 serious adverse event (erysipelas) were reported in the BID regimen. No pts discontinued in the first 9 weeks, no deaths in this period. Conclusions: Following the results of the run-in phase, the BID regimen was chosen for the ongoing study. [Table: see text] [Table: see text]

A pilot study of levetiracetam as a sensitizer of temozolomide for newly diagnosed glioblastoma: A prospective, open-label, phase II study (KBTS-1601 study).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2560-2560
Author(s):  
Chae-Yong Kim ◽  
Kihwan Hwang ◽  
Jong Hee Chang ◽  
Seok-Gu Kang ◽  
Tae-Young Jung ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Median Overall Survival ◽  
Phase Ii Study ◽  
Performance Status ◽  
Control Group ◽  
Newly Diagnosed ◽  
Open Label ◽  
Adjuvant Temozolomide ◽  
Newly Diagnosed Glioblastoma

2560 Background: We evaluated the survival benefit of levetiracetam as a chemosensitizer of temozolomide for patients with newly diagnosed glioblastoma. Methods: This was an open-label, multicenter, phase II study (NCT02815410). Eligible patients were aged 18 years or older and had newly diagnosed glioblastoma with an ECOG performance status of 0-2. All patients received 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). The first dose of levetiracetam was given just after the surgery at 250mg orally twice a day and increased up to 500mg twice a day prior to radiation. This prospective study was designed to test whether levetiracetam in conjunction with temozolomide improved survival. The historical control group was based on data from a study by Gwak et al. for Korean patients with newly diagnosed glioblastoma with a median overall survival(OS) of 17.5 months and a median progression-free survival (PFS) of 10.1 months. Results: Forty-six patients were enrolled between August 2016 and January 2019. The median follow-up duration was 24.9 months (range, 7.9-35.5). All patients completed standard radiation therapy with temozolomide, and 39 (84.8%) patients completed six cycles of adjuvant temozolomide. Median overall survival (OS) was 30.0 months, and median PFS was 15.0 months. OS at 6, 12, and 24 months was 100%, 91.3%, and 60.7%, respectively. PFS at 6, 12, and 24 months was 93.2%, 65.3%, and 22.6%, respectively. Conclusions: Addition of levetiracetam during concurrent and adjuvant temozolomide along with radiotherapy in patients with newly diagnosed glioblastoma may result in improved outcomes compared to historical data and merits further study. Clinical trial information: NCT02815410 .

A phase II study of anlotinib combined with STUPP regimen in the treatment of patients with newly diagnosed glioblastoma (GBM).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2039-2039
Author(s):  
Peijing Li ◽  
Yuan yuan Yuan Chen ◽  
Shuzhen Lai ◽  
Fagui Jiang ◽  
Xiaohui Liu ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Open Label ◽  
Who Grade ◽  
Common Grade ◽  
Grade 3

2039 Background: STUPP regimen is now the standard treatment for newly diagnosed GBM, while the effectiveness is limited. This study assessed the efficacy and safety of anlotinib, a multitarget tyrosine kinase inhibitor, combined with the STUPP regimen in treating these patients. Methods: This is a phase II, multicenter, open-label, single-arm trial (NCT04119674). Thirty-three patients (17 males and 16 females) were enrolled from 8 hospitals in China between January 2019 and February 2021. Inclusion criterion included 1) newly diagnosed histologically confirmed glioblastoma (WHO grade IV), 2) 2-6 weeks (wks) after surgery with healed incision, 3) 18-70 years old, 4) KPS≥60, 5) at least one measurable lesion according to RANO criteria, 6) radiotherapy (RT), chemotherapy, immunotherapy or biotherapy naïve. All patients received 54-60 Gy radiation (1.8-2.0 Gy per fraction, five days per week) concurrently with temozolomide (TMZ, 75mg/m2, orally, QD) and anlotinib (8mg, orally, QD, d1-14/3wks). Adjuvant therapy started four weeks after RT completion, including six cycles of TMZ (150-200mg/m², orally, d1-5/4wks) and eight cycles of anlotinib (8mg, orally, QD, d1-14/3wks). Patients who completed adjuvant therapy were administrated anlotinib continuously until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Safety assessment was done in patients who received at least one dose of study agent. Results: The median age is 52 (range 32-69) years. Analyses included data collected through February 6, 2021. The median treatment duration was 6.5 months. The median PFS was not reached, and the median overall survival (OS) was 17.4 months [95%CI 11.6-23.2]. The 1-year PFS and OS rate was 84.0% and 100.0%, respectively. Tumor response occurred in 21 patients, 63.6% (21/33) objective response (CR/PR), and 24.2% (8/33) patients had stable disease (SD).The clinical benefit rate (CBR), defined as the proportion of patients who achieved durable disease control (CR/PR/SD) more than six months, was 57.6% (19/33). Hypertension (6.1%) was the most common ≥grade 3 adverse event. No treatment related death occurred in this study through the last follow-up. Overall, toxicities are mild and manageable. Conclusions: Anlotinib combined with the STUPP regimen is efficacious and well-tolerated in newly diagnosed GBM patients. Clinical trial information: NCT04119674.

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