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

scholarly journals Randomized Phase II Trial of Chemoradiotherapy Followed by Either Dose-Dense or Metronomic Temozolomide for Newly Diagnosed Glioblastoma

2009 ◽  
Vol 27 (23) ◽  
pp. 3861-3867 ◽  
Author(s):  
Jennifer L. Clarke ◽  
Fabio M. Iwamoto ◽  
Joohee Sul ◽  
Katherine Panageas ◽  
Andrew B. Lassman ◽  
...  
Keyword(s):  
Phase Ii ◽  
Dna Methyltransferase ◽  
Methylation Status ◽  
Progression Free Survival ◽  
Therapeutic Index ◽  
Newly Diagnosed ◽  
Randomized Phase Ii ◽  
Elevated Liver Enzymes ◽  
Newly Diagnosed Glioblastoma ◽  
Dose Dense

Purpose Alternative dosing schedules of temozolomide may improve survival in patients with newly diagnosed glioblastoma (GBM) by increasing the therapeutic index, overcoming common mechanisms of temozolomide resistance, or both. The goal of this randomized phase II study was to evaluate two different temozolomide regimens in the adjuvant treatment of newly diagnosed GBM. Patients and Methods Adult patients with newly diagnosed GBM were randomly assigned to receive standard radiotherapy with concurrent daily temozolomide followed by six adjuvant cycles of either dose-dense (150 mg/m2 days 1 to 7 and 15 to 21) or metronomic (50 mg/m2 continuous daily) temozolomide. Maintenance doses of 13-cis-retinoic acid were then administered until tumor progression. The primary end point was overall survival (OS) at 1 year. Tumor tissue was assayed to determine O6-methylguanine–DNA methyltransferase (MGMT) promoter methylation status. Results Eighty-five eligible patients were enrolled; 42 were randomly assigned to dose-dense and 43 to metronomic temozolomide. The 1-year survival rate was 80% for the dose-dense arm and 69% for the metronomic arm; median OS was 17.1 months (95% CI, 14.0 to 28.1 months) and 15.1 months (95% CI, 12.3 to 18.9 months), respectively. The most common toxicities were myelosuppression (leukopenia, neutropenia, and thrombocytopenia) and elevated liver enzymes. Pseudoprogression was observed in 37% of assessable patients and may have had an impact on estimates of progression-free survival (6.6 months in the dose-dense arm and 5.0 months in the metronomic arm). Conclusion Both dose-dense and metronomic temozolomide regimens were well tolerated with modest toxicity. The dose-dense regimen appears promising, with 1-year survival of 80%.

Five-year survival data in newly diagnosed glioblastoma treated with radiotherapy along with concurrent and adjuvant temozolomide

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13009-e13009
Author(s):  
T. Wadasadawala ◽  
R. Jalali ◽  
A. Munshi ◽  
T. Gupta ◽  
N. Kalyani ◽  
...  
Keyword(s):  
Survival Data ◽  
Recursive Partitioning ◽  
Progression Free Survival ◽  
Karnofsky Performance Score ◽  
Newly Diagnosed ◽  
Performance Score ◽  
Adjuvant Temozolomide ◽  
Newly Diagnosed Glioblastoma ◽  
Grade 3

e13009 Background: We report 5-year survival data in patients with newly diagnosed glioblastoma treated with radiotherapy along with concurrent and adjuvant temozolomide (TMZ). Methods: Between March 2001 to April 2008, 81 patients with newly diagnosed histopathologically proven glioblastoma underwent surgery followed by external radiotherapy to a total dose of 60 Gy in 30 fractions over 6 weeks. Concurrent oral TMZ (75 mg/m2) was given daily with RT followed by adjuvant TMZ for 5 days every 28 days for six cycles (150 mg/m2 for the first cycle and 200 mg/m2 for rest of the cycles). Patients were monitored clinicoradiologically as per standard practice. Results: Patients aged between 11–73 years with a median age of 49 years (60 males, 21 females). Forty per cent of patients underwent a gross total resection of tumour, 44% had partial resection, and 16% an open or stereotactic biopsy only. 79% of the patients had a post-operative Karnofsky Performance Score (KPS) of >80. All six adjuvant cycles were completed in 68%. The 2-, 3-, 4-, and 5-year survival was 34%, 24%, 11%, and 11%, respectively (95% CI 14.03–21.96). The median overall and progression-free survival was 18 (2–92 months) and 16 months (2–72 months), respectively. On multivariate analysis, completion of all six cycles of adjuvant TMZ was associated with significantly better survival (p = 0.000). Neurological performance score (NPS) of 2–3 (p = 0.06) and Recursive Partitioning Analysis class V (p = 0.093) showed a trend towards poorer outcome. Treatment was generally well tolerated with only 2.5% of patients developing grade 3 anemia, leucopoenia, and neutropenia. Grade 3 or 4 thrombocytopenia was seen in 5% patients. Conclusions: Concurrent radiotherapy and TMZ followed by adjuvant TMZ results in encouraging survival even at a long follow-up. No significant financial relationships to disclose.

scholarly journals A multi-institution phase II study of poly-ICLC and radiotherapy with concurrent and adjuvant temozolomide in adults with newly diagnosed glioblastoma

2010 ◽  
Vol 12 (10) ◽  
pp. 1071-1077 ◽  
Author(s):  
M. R. Rosenfeld ◽  
M. C. Chamberlain ◽  
S. A. Grossman ◽  
D. M. Peereboom ◽  
G. J. Lesser ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Newly Diagnosed ◽  
Adjuvant Temozolomide ◽  
Newly Diagnosed Glioblastoma

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 Survival benefits of hypofractionated radiotherapy combined with temozolomide or temozolomide plus bevacizumab in elderly patients with glioblastoma aged ≥ 75 years

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Makoto Ohno ◽  
Yasuji Miyakita ◽  
Masamichi Takahashi ◽  
Hiroshi Igaki ◽  
Yuko Matsushita ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Dna Methyltransferase ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Methylation Status ◽  
Progression Free Survival ◽  
Promoter Hypermethylation ◽  
Hypofractionated Radiotherapy ◽  
Methylguanine Dna Methyltransferase ◽  
Grade 3

Abstract Background and purpose The purpose of this study was to evaluate the outcomes of elderly patients (aged ≥75 years) with newly diagnosed glioblastoma (GBM), who were treated with hypofractionated radiotherapy comprising 45 Gy in 15 fractions combined with temozolomide (TMZ) or TMZ and bevacizumab (TMZ/Bev). Materials and methods Between October 2007 and August 2018, 30 patients with GBM aged ≥75 years were treated with hypofractionated radiotherapy consisting of 45 Gy in 15 fractions. Twenty patients received TMZ and 10 received TMZ/Bev as upfront chemotherapy. O-6-methylguanine DNA methyltransferase (MGMT) promoter methylation status was analyzed by pyrosequencing. The cutoff value of the mean level of methylation at the 16 CpG sites was 16%. Results Median overall survival (OS) and progression-free survival (PFS) were 12.9 months and 9.9 months, respectively. The 1-year OS and PFS rates were 64.7 and 34.7%, respectively. Median OS and PFS did not differ significantly between patients with MGMT promoter hypermethylation (N = 11) and those with hypomethylation (N = 16) (17.4 vs. 11.8 months, p = 0.32; and 13.1 vs. 7.3 months, p = 0.11, respectively). The median OS and PFS were not significantly different between TMZ (N = 20) and TMZ/Bev (N = 10) chemotherapy (median OS: TMZ 12.9 months vs. TMZ/Bev 14.6 months, p = 0.93, median PFS: TMZ 8.5 months vs TMZ/Bev 10.0 months, p = 0.64, respectively). The median time until Karnofsky performance status (KPS) score decreasing below 60 points was 7.9 months. The best radiological responses included 11 patients with a partial response (36.7%). Grade 3/4 toxicities included leukopenia in 15 patients (50%), anorexia in 4 (13.3%), and hyponatremia during concomitant chemotherapy in 3 (10%). Conclusion Our hypofractionated radiotherapy regimen combined with TMZ or TMZ/Bev showed benefits in terms of OS, PFS, and KPS maintenance with acceptable toxicities in elderly patients with GBM aged ≥75 years.

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.

Full Dose Vincristine (V) Negatively Impacts Progression Free Survival in Newly Diagnosed or Relapsed/Refractory Multiple Myeloma Patients Treated with Pegylated Doxorubicin, Vincristine, Reduced-Dose Dexamethasone, and Thalidomide (DVd-T).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2570-2570
Author(s):  
R. Suppiah ◽  
E. Walker ◽  
K. Almhanna ◽  
S. Andresen ◽  
J. Reed ◽  
...  
Keyword(s):  
Phase Ii ◽  
Overall Response Rate ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Full Dose ◽  
Grade 3 ◽  
Positive Effect

Abstract Background: The activity of V in myeloma was first described in the 1970’s. Although Phase II data suggest that V demonstrates single agent activity, subsequent reports have questioned its role. Due to these conflicting results, we conducted a subanalysis investigating the effect of V dose in the phase II DVd-T regimen that we have previously reported (Agrawal et al ASH 2003). We evaluated the effects of V dose on progression free survival (PFS) and overall survival (OS) in newly diagnosed and relapsed/refractory patients treated with DVd-T. Patients and Methods: As previously reported, this Phase II study enrolled 102 patients with newly diagnosed or relapsed/refractory multiple myeloma with evidence of end organ damage. DVd-T was administered as previously reported. After best response, patients were maintained on prednisone 50mg every other day and the maximum tolerated dose of thalidomide until disease progression. For patients experiencing grade 1 neuropathy, V was reduced by 25%, and for grade 2, by 50%. Patients developing grade 3/4 neuropathy had V discontinued and thalidomide suspended until toxicity decreased by at least one grade. Univariate analyses were conducted to assess the effect of V dose reduction or elimination on PFS and OS. Multivariate analyses were performed to adjust for the impact of age, platelet count, stage, quality of response (CR or near CR versus SD or PR), and thalidomide dose. Results: Trial included 53 newly diagnosed and 49 relapsed/refractory patients. Median age was 62.9 years. 59% had stage 3 or 4 disease. 37% had abnormal cytogenetics. Median beta-2 microglobulin was 4.1. Overall response rate of 87% was seen in newly diagnosed patients (36% achieved CR; 13% near CR; 38% PR; 8% SD; 6% PD). In the relapsed/refractory patients, overall response rate of 87% was achieved (21% achieved CR; 26% near CR; 40% PR; 13% SD). Median follow up was 28.1 months. Median PFS for the newly diagnosed group was 28.2 months and 15.5 for the relapsed/refractory group. Median OS was 39.9 months for the relapsed/refractory group. After 50 months of follow-up for the newly diagnosed group, median OS has not been reached. In total, 464 cycles were administered, of which 225 were given with full dose V and 242 with reduced dose or eliminated V. Grade 3/4 neuropathy occurred in 22 patients. Univariate analysis revealed that reducing or eliminating V had a significant positive effect on PFS and OS (p = 0.0002 and 0.02 respectively). Multivariate analysis adjusting for age at start of study, platelet count, stage, quality of response [CR or near CR versus SD or PR], and thalidomide dose, similarly found that reducing or eliminating the dose of V had a significant positive effect (p = 0.0121) on PFS. However, multivariate analysis did not reveal the same effect on OS (p = 0.11). Conclusions: This subanalysis suggests that the use of full dose V in the DVd-T regimen may have a negative effect on PFS. The exact mechanism by which V affects PFS is not clear. Studies are now on-going investigating this regimen without V. Figure Figure

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