A retrospective safety and efficacy analysis of combination therapy using Gliadel wafers plus external beam radiation therapy with concurrent temozolomide in newly diagnosed glioblastoma multiforme patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 12510-12510
Author(s):  
E. Pan ◽  
S. B. Mitchell ◽  
J. S. Tsai
Keyword(s):  
Glioblastoma Multiforme ◽  
Clinical Outcomes ◽  
Multimodal Therapy ◽  
Small Sample ◽  
External Beam Radiation ◽  
Newly Diagnosed ◽  
Beam Radiation ◽  
Safety And Efficacy ◽  
Newly Diagnosed Glioblastoma ◽  
Grade 3

12510 Background: Safety and efficacy of malignant glioma treatment with carmustine-containing biodegradable implants (Gliadel® Wafers) followed by conventional radiotherapy (RT) and treatment with RT and concomitant temozolomide have both been well established. Multimodal therapy combining Gliadel® Wafers, RT, and temozolomide has recently demonstrated significant improvements in clinical outcomes of newly-diagnosed glioblastoma multiforme (GBM) patients. However, Gliadel® Wafer implantation in newly-diagnosed GBM patients is limited by the suspected risk of toxicities associated with multimodal therapy. Thus, the safety of multimodal therapy with Gliadel® Wafers, RT, and temozolomide needs to be determined. Methods: We conducted a retrospective analysis of medical records of 21 Florida Hospital Neuro- Oncology Center patients who were newly diagnosed with GBM from January 2003 to December 2005 and initially received multimodal therapy. All systemic and local toxicities were graded according to CTC AE v.3.0. Results were compared to historical data. Results: Our study population did not differ significantly from prior study populations with regard to patient demographics. 4 of 21 (19%) patients had grade 3 toxicities, which may have been related to multimodal therapy. None of the 21 patients had grade 4 toxicities. Median time to progression from initial surgery was 12.8 months (range 2–24 months). Median overall survival was 17 months (95% CI of 15–25 months). Conclusion: The addition of Gliadel® Wafers to concurrent RT and temozolomide did not result in a notable increase in grade 3 and 4 toxicities but did produce clinical outcomes comparable with those found in prior studies. The small sample size does not allow for definitive conclusions regarding efficacy. However, the addition of Gliadel® Wafers to concurrent RT and temozolomide appears to be safe in newly-diagnosed GBM patients. [Table: see text] No significant financial relationships to disclose.

CTNI-59. A MULTICENTER OBSERVATIONAL STUDY OF CS-131 SEEDS EMBEDDED IN A COLLAGEN CARRIER TILE FOR NEWLY DIAGNOSED AND RECURRENT OPERABLE INTRACRANIAL NEOPLASMS – TRIAL IN PROGRESS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi74-vi74
Author(s):  
Erin Dunbar ◽  
David McCracken ◽  
adam nowlan ◽  
Clark Chen ◽  
Kathryn Dusenbery ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Adverse Events ◽  
Clinical Outcomes ◽  
Real World ◽  
External Beam Radiation ◽  
Newly Diagnosed ◽  
Intracranial Neoplasms ◽  
Safety And Efficacy ◽  
Patient Reported

Abstract BACKGROUND For patients with operable intracranial neoplasms, there are opportunities to augment local control beyond traditional methods, such as external beam radiation therapy. Brachytherapy, the implantation of radioactive sources into the resection cavity, can be useful in this setting by providing immediate initiation of radiation and limiting the exposure of surrounding normal tissue to radiation. Traditional intracranial brachytherapy has been limited by uneven dose distributions, complicated workflows, extended procedural times, cost of dedicated equipment, and frequent adverse events. To address these issues, a permanently implanted device with Cs-131 radiation seeds embedded in a bioresorbable collagen carrier tile (GammaTile, GT Medical Technologies, Tempe, AZ USA) was developed. Described as surgically targeted radiation therapy (STaRT), it is FDA-cleared for use in newly-diagnosed malignant intracranial neoplasms and recurrent intracranial tumors, and has demonstrated excellent safety and efficacy in early commercial use. The primary objectives of this multicenter, prospective, observational (phase IV) registry study are to evaluate “real-world” clinical outcomes and patient-reported outcomes that measure the safety and efficacy of STaRT using the GammaTile. METHODS Patients undergoing resection (R) of brain tumors with intra-operative GammaTile placement are eligible for enrollment. Planned sample size is 600 at up to 50 enrolling sites. First subject was enrolled 10/14/2020. Tumor pathology, overall survival, radiation- and surgery-related adverse events, patient- and provider-reported quality of life, serial MRIs, and timing of surgical bed and/or distant recurrence are collected. Powered primary endpoints for recurrent brain metastases, recurrent glioblastoma, and recurrent meningioma (surgical bed-progression free survival (PFS), overall survival, and PFS, respectively), compare STaRT to standard-of-care benchmarks. Results will be used to improve awareness and access to this treatment, benchmark clinical outcomes in the real-world setting, allow for comparisons to existing treatments, facilitate the design of future clinical trials, and contribute to the optimal sequencing of treatments for intracranial neoplasms.

scholarly journals HOUT-02. TREATMENT PATTERNS AND OUTCOMES FOR PATIENTS WITH NEWLY-DIAGNOSED GLIOBLASTOMA MULTIFORME IN A US COMMUNITY ONCOLOGY SETTING

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi112-vi112
Author(s):  
Alex Fu ◽  
Nicholas Robert ◽  
Trang Pham ◽  
Alexander Marshall ◽  
Srinivas Annavarapu
Keyword(s):  
Glioblastoma Multiforme ◽  
Clinical Outcomes ◽  
Dna Methyltransferase ◽  
Treatment Options ◽  
Methylation Status ◽  
Treatment Patterns ◽  
Newly Diagnosed ◽  
Mgmt Methylation ◽  
The Us ◽  
Newly Diagnosed Glioblastoma

Abstract BACKGROUND This study aims to describe real world characteristics and outcomes of newly-diagnosed glioblastoma multiforme (GBM) patients in relationship to O6-methylguanine DNA methyltransferase promoter (MGMT) testing and methylation status, in the US. METHODS Patients receiving care for GBM were identified in the US Oncology Network database from 1/1/2013 to 6/30/2018 and followed up to 9/30/2018. Structured data and chart reviews were used to assess demographic and clinical characteristics, treatment patterns, type of surgery, MGMT methylation, and clinical outcomes. RESULTS Of 600 patient charts planned for review, 195 have been randomly selected and reviewed thus far. Of these, 165 (84.6%) had surgical resection and 30 (15.4%) had biopsy only. Eighty-eight (45.1%) patients were tested for MGMT status and 107 (54.9%) were not. Of those tested, 33 (37.5%) were methylated, and 45 (51.1%) unmethylated. Median ages in the overall (including tested and untested), methylated and unmethylated cohorts were 63.7, 58.8, and 66.7 years, respectively. Most common first-line (1L) treatment in overall, methylated, and unmethylated cohorts was radiation concurrent with temozolomide received by 86.2%, 93.9%, and 91.1%, respectively. Median duration of 1L treatment in the overall cohort was 15.1 weeks (95% confidence interval [CI]: 11.9, 21.6) and higher in the methylated vs. unmethylated cohort (25.9 [18.1, 34.6] vs. 15.1 [9.3, 23.4] weeks, p=0.0375). Unadjusted median overall survival and progression-free survival in the overall cohort were 11.4 [9.4, 14.0] months and 5.2 [3.9, 5.8] months, and higher in the methylated vs. unmethylated cohort (20.5 [14.9, not realized] vs. 12.2 [7.1, 17.0] months, p=0.0052, and 9.4 [5.6, 14.0] vs. 5.5 [3.3, 6.8], p=0.0092, respectively). CONCLUSIONS Fewer than half of GBM patients were tested for MGMT methylation in the US community. Clinical outcomes, while better among patients with methylated MGMT, remain poor and current treatment options are limited.

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.

A phase II study of chemoradiation followed by adjuvant temozolomide and poly-ICLC in patients with newly diagnosed glioblastoma: 12- and 18-month survival data (NABTT 0501)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2002-2002
Author(s):  
M. R. Rosenfeld ◽  
M. Chamberlain ◽  
S. A. Grossman ◽  
D. M. Peereboom ◽  
G. J. Lesser ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adjuvant Treatment ◽  
Survival Data ◽  
Cell Activation ◽  
Killer Cell ◽  
External Beam Radiation ◽  
Newly Diagnosed ◽  
Beam Radiation ◽  
Entire Cohort ◽  
Newly Diagnosed Glioblastoma

2002 Background: Polyinosinic-polycytidylic (poly-ICLC), is a double-stranded RNA that stimulates a variety of host defense mechanisms including T-cell and natural killer cell activation, cytokine release and specific anti-proliferative and anti-viral effects. The objective of this study was to determine the safety and efficacy of poly-ICLC when added to adjuvant treatment for newly diagnosed glioblastoma. Methods: Newly diagnosed patients > 18 years with histologically proven glioblastoma received standard external beam radiation with concurrent low-dose temozolomide (TMZ) (75 mg/m2) followed by adjuvant cycles of TMZ for 5 days (150–200 mg/m2) (week 1) then intramuscular injections of poly-ICLC (20 mcg/kg) 3 times a week (weeks 2–8; total 21 injections) with week 9 off and no limit to the number of adjuvant cycles (TMZ + poly-ICLC). Imaging evaluations were performed before every cycle. Results: There were 97 patients enrolled (60 men); median age 56 yrs (range 21–85); median KPS 90 (range 60–100). Fourteen patients did not start adjuvant treatment (5 patient request and 4 investigator withdrawal; 2 progressive disease; 1 death; 1 toxicity; 1 other). The most frequent CTC grade 3–4 toxicities occurring in > 5% of subjects at least possibly related to poly-ICLC were leukopenia (20%), thrombocytopenia (14%), anemia (13%), neutropenia (10%), and SGPT (9%) or alkaline phosphatase (7%) elevation. Two deaths during adjuvant treatment were considered unlikely related to poly-ICLC. To date 71 of 97 patients have survived at least 12 months from diagnosis. The estimated median survival for the entire cohort was 17.2 months (95% CI: 15.5–19.3 months). Overall survival for the cohort at 12 months was 73.2% (95% CI: 63%-82%) and at 18 months 47.4% (95% CI: 37–58%). For only those subjects 18–70 years, overall survival at 18 months was 51.8% (95% CI: 41–63%). This is contrasted with EORTC 26981/22981 that reported an 18 month overall survival of 39.4% (95% CI: 33.8–45.1). Conclusions: The addition of poly-ICLC to a modified adjuvant treatment regimen for newly diagnosed GB is well-tolerated. Survival data at 12 and 18 months suggest increased efficacy compared to chemoradiation with adjuvant TMZ only. [Table: see text]

Outcome of grade 3 and 4 cytopenia in newly diagnosed glioblastoma multiforme (GBM) patients treated with temozolomide (TMZ).

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 2018-2018
Author(s):  
B. E. Sanchez ◽  
J. Munoz ◽  
H. Y. Ali ◽  
J. M. Anderson ◽  
P. Kuriakose
Keyword(s):  
Glioblastoma Multiforme ◽  
Newly Diagnosed ◽  
Newly Diagnosed Glioblastoma ◽  
Grade 3

A phase II trial of radiation and cetuximab followed by irinotecan/cetuximab for children with newly diagnosed diffuse pontine tumors and high-grade astrocytomas.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10030-10030 ◽  
Author(s):  
Margaret Macy ◽  
Mark W. Kieran ◽  
Susan N. Chi ◽  
Kenneth J. Cohen ◽  
Tobey MacDonald ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Phase 1 ◽  
Progression Free Survival ◽  
External Beam Radiation ◽  
High Grade ◽  
Newly Diagnosed ◽  
Beam Radiation ◽  
Phase 2 Trial ◽  
Correlative Studies ◽  
Grade 3

10030 Background: Diffuse intrinsic pontine gliomas (DIPG) and high-grade astrocytomas (HGA) have dismal prognoses. We previously demonstrated in a phase 1 study that cetuximab and irinotecan was a safe and tolerable regimen. Consequently, we initiated this 2-strata phase 2 trial to investigate the safety and efficacy of weekly cetuximab given with involved field external beam radiation therapy followed by 10 cycles of cetuximab and irinotecan for DIPG and HGA as determined by the 1-year progression-free survival. Methods: Eligible patients aged 3-21 years with newly diagnosed HGA or DIPG were enrolled to parallel strata. All patients received radiation therapy (5940 cGy) with concurrent cetuximab at 250mg/m2 IV weekly for 6 weeks. Following radiation, patients received cetuximab (250mg/m2 IV) weekly and irinotecan (16mg/m2/day IV) daily x 5 for two weeks every 21 days for 30 weeks. Tumor, serum, and CSF samples were collected for correlative studies. Sera collected at the onset of rash were analyzed for inflammatory and immune-related cytokines. Results: Forty-eight patients (27 DIPG, 21 HGA) were enrolled and 45 were treated (median age 8 years; range: 3–19). Toxicities were manageable; the most common adverse events were fatigue, gastrointestinal complaints, neutropenia, rash, headache, electrolyte abnormalities, elevated ALT/AST, and fever. Grade 3-4 events in ≥10% of patients were hypokalemia and lymphopenia. 4 patients experienced cetuximab-related hypersensitivity reactions (2 grade 3 reactions). The median PFS was 9.5 months (95% CI: 7.0-12.2) for HGA and 7.8 months (7.0-8.6) for DIPG with a 1-year PFS±SE of 24±10% and 25%±10% respectively. The median OS for HGA was 17.7 months (95% CI: 14.1-18.0) and 11.5 months (8.8-14.2) for DIPG. Biological correlative studies will be presented. Conclusions: Cetuximab and radiation therapy followed by cetuximab and irinotecan is well tolerated in children. Based on the 1-year PFS, this regimen may deserve further investigation in patients with DIPG. Biological correlative studies will delineate the mechanisms of the rash and possible implications for EGFR-targeted therapeutics in such patients. Clinical trial information: NCT01012609.

CONVECTION-ENHANCED DELIVERY OF CINTREDEKIN BESUDOTOX (INTERLEUKIN-13-PE38QQR) FOLLOWED BY RADIATION THERAPY WITH AND WITHOUT TEMOZOLOMIDE IN NEWLY DIAGNOSED MALIGNANT GLIOMAS

Neurosurgery ◽  
2007 ◽  
Vol 61 (5) ◽  
pp. 1031-1038 ◽  
Author(s):  
Michael A. Vogelbaum ◽  
John H. Sampson ◽  
Sandeep Kunwar ◽  
Susan M. Chang ◽  
Mark Shaffrey ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Malignant Gliomas ◽  
External Beam Radiation ◽  
Newly Diagnosed ◽  
Convection Enhanced Delivery ◽  
Beam Radiation ◽  
Interleukin 13 ◽  
Grade 3 ◽  
Dose Limiting Toxicity ◽  
Final Cohort

Abstract OBJECTIVE Cintredekin besudotox (CB), a recombinant cytotoxin consisting of interleukin-13 and truncated Pseudomonas exotoxin, binds selectively to interleukin-13Rα2 receptors overexpressed by malignant gliomas. This study assessed the safety of CB administered by convection-enhanced delivery followed by standard external beam radiation therapy (EBRT) with or without temozolomide (Temodar; Schering-Plough, Kenilworth, NJ) in patients with newly diagnosed malignant gliomas. METHODS After gross total resection of the tumor, two to four intraparenchymal catheters were stereotactically placed and CB (0.25 or 0.5 μg/mL) was infused for 96 hours. This was followed, 10 to 14 days later, by EBRT (5940–6100 cGy, 5 d/wk for 6–7 wk) with or without temozolomide (75 mg/m2/d, 7 d/wk during EBRT). Safety was assessed during an 11-week observation period after catheter placement RESULTS Twenty-two patients (12 men, 10 women; median age, 55 yr; 21 with glioblastoma multiforme and one with an anaplastic mixed oligoastrocytoma) were enrolled. None of the patients experienced dose-limiting toxicities in the first two cohorts (0.25 μg/mL CB + EBRT [n = 3] and 0.25 μg/mL CB + EBRT + temozolomide [n = 3]). One patient experienced a dose-limiting toxicity (Grade 4 seizure) in the third cohort (0.5 μg/mL CB + EBRT [n = 6]). Six patients in the final cohort (0.5 μg/mL CB + EBRT + temozolomide [n = 10]) completed treatment, and one patient experienced a dose-limiting toxicity (Grade 3 aphasia and confusion). Four patients were not considered evaluable for a dose decision and were replaced. CB related adverse events occurring in more than one patient were fatigue, gait disturbance, nystagmus, and confusion. No Grade 3 to 4 hematological toxicities were observed. CONCLUSION CB (0.5 μg/mL) administered via convection-enhanced delivery before standard radiochemotherapy seems to be well tolerated in adults with newly diagnosed malignant gliomas. Further clinical study assessment is warranted.

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