INNV-14. PREDICTIVE UTILITY OF TEMOZOLOMIDE RESPONSE AS DETERMINED BY 3D EX-VIVO CELL CULTURE ASSAYS IN NEWLY DIAGNOSED GLIOBLASTOMA: A SINGLE INSTITUTION CASE SERIES EVALUATING PROGRESSION FREE SURVIVAL

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi108-vi108
Author(s):  
Lindsay J Lipinski ◽  
Ajay Abad ◽  
Robert A Fenstermaker ◽  
Andrew J Fabiano ◽  
Dheerendra Prasad ◽  
...  
Keyword(s):  
Cell Culture ◽  
Ex Vivo ◽  
Short Interval ◽  
Methylation Status ◽  
Case Series ◽  
Patient Specific ◽  
Newly Diagnosed ◽  
Single Institution ◽  
Number Of Patients ◽  
Newly Diagnosed Glioblastoma

Abstract Glioblastoma is an aggressive tumor that is clinically and pathologically heterogeneous, and as such, remains challenging to treat. Response to initial standard treatment is widely variable and patient specific. We describe a cohort of 11 newly diagnosed patients enrolled in the 3D-PREDICT study at a single institution who underwent maximal safe surgical resection with tumor tissue collected prospectively for ex vivo cell culture assays against a panel of commonly used agents, including temozolomide. Nine of eleven patients received concurrent radiation + temozolomide followed by adjuvant temozolomide as per current standard of care. Two patients progressed immediately following concurrent chemoradiation; pseudoprogression was ruled out with short interval repeat imaging and clinical deterioration with pathology confirming recurrent tumor on re-resection in one patient. Median follow-up was 10 months (range 2-18). Outcomes were assessed retrospectively using Kaplan-Meier time-to-event curves, separating into two groups the temozolomide responders (n=4) and temozolomide nonresponders (n=7), as defined by the previously validated assay. The event was reached when radiographic tumor recurrence/progression occurred. Due to limited sample size, statistical significance was not reached, but a trend toward longer time to recurrence was noted among the temozolomide responder group. Continued experience with this tool may help clinicians predict which patients with newly diagnosed glioblastoma will respond well to initial treatment with temozolomide and those that may be more appropriate for clinical trial enrollment, independent of MGMT promoter methylation status. Longer term studies with a larger number of patients will help to determine the true significance of this drug response prediction assay.

scholarly journals INNV-16. CLINICAL APPLICABILITY OF INDIVIDUALIZED DRUG RESPONSE PROFILING UTILIZING EX-VIVO TISSUE-DERIVED 3D CELL CULTURE ASSAYS IN HIGH-GRADE GLIOMA: A SINGLE INSTITUTION CASE SERIES USING 3D-PREDICT RESULTS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii119-ii120
Author(s):  
Lindsay Lipinski ◽  
Ajay Abad ◽  
Laszlo Mechtler ◽  
Andrew Fabiano ◽  
Ashley Smith ◽  
...  
Keyword(s):  
Cell Culture ◽  
Drug Response ◽  
Ex Vivo ◽  
Performance Status ◽  
Case Series ◽  
3D Cell Culture ◽  
High Grade Glioma ◽  
Patient Specific ◽  
High Grade ◽  
Ex Vivo Tissue

Abstract Recurrent high-grade glioma is a challenging disease process, without consensus on effective second-line therapy options. Individualized, patient-specific, biologically-based data is desirable in driving therapeutic decision-making. Patients with recurrent high-grade glioma and planned surgical re-resection at our institution were prospectively enrolled into the 3D-PREDICT study. Tissue was collected at the time of surgery for ex vivo 3D cell culture assays comprising a panel of agents commonly used for high-grade glioma, including chemotherapies and targeted therapies used in other solid cancers. In all cases, therapeutic agent selection was guided by the neuro-oncologist’s clinical judgement, factoring the patient’s age, performance status, comorbidities, toxicities/side effect profile of potential agents, and drug accessibility, plus ex-vivo drug response RESULTS: We present 3 cases in which the selection of agents was influenced by the tissue-derived 3D cell culture results; treatment led to clinical response observed in terms of progression free survival, quality of life, and pharmacologic tolerability. In Case 1, a patient with recurrent anaplastic astrocytoma was treated with a BRAF inhibitor for 12 months with excellent tolerability and no radiographic progression. Case 2 demonstrates the use of combination bevacizumab and irinotecan after disease progression subsequent to standard treatment. This patient had local radiographic control for 7 months, tolerating the regimen well. In Case 3, an individual with recurrent glioblastoma was treated with combination carboplatin and etoposide based on assay response prediction to both agents; treatment has been tolerated well with radiographic stability at 6 months while maintaining good performance status. This case series represents our institutional experience of utilizing patient-specific, ex-vivo tissue-derived cell drug response profiling to guide choice of therapy for recurrent high-grade glioma patients. Using individualized, tumor-specific drug sensitivity data to guide these decisions is representative of the ongoing paradigm shift into the realm of individualized medicine to improve outcomes in cancer patients.

scholarly journals P14.61 Tumor Treating Fields (TTFields) combined with lomustine (CCNU) and temozolomide (TMZ) in newly diagnosed glioblastoma (GBM) patients - a bi-centric analysis

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii81-iii81
Author(s):  
L Lazaridis ◽  
N Schäfer ◽  
T Schmidt ◽  
A Stoppek ◽  
J Weller ◽  
...  
Keyword(s):  
Combined Therapy ◽  
Performance Status ◽  
Methylation Status ◽  
Case Series ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Skin Reactions ◽  
Term Survival ◽  
Tumor Treating Fields ◽  
Newly Diagnosed Glioblastoma

Abstract BACKGROUND TTFields combined with TMZ demonstrated significantly improved PFS, OS and long-term survival in newly diagnosed glioblastoma (ndGBM) patients, compared to TMZ monotherapy in the EF-14 trial; independent of MGMT-promotor methylation-status, age, grade of resection and performance status. Recently, improved efficacy of lomustine (CCNU)/TMZ compared to TMZ monotherapy in ndGBM patients with MGMT-promotor methylation was reported in the CeTeG trial (NOA-09). Taken into account that TTFields showed a strong safety profile as well as a high potential being combined with other modalities and the very encouraging results for methylated MGMT-promotor GBM patients in the CeTeG trial, there is a strong rationale in combining these treatment regimens. Here, we present a case series of patients receiving a combination of both modalities, TTFields and CCNU/TMZ. METHODS Patients with ndGBM and MGMT-promotor methylation underwent a combined therapy of TTFields plus CCNU/TMZ after surgery and radiochemotherapy. Safety, feasibility as well as first efficacy results of this combined therapy are reported at data cut-off (31.12.2018). Most recent data, including compliance to TTFields therapy, will be presented at the EANO annual meeting. RESULTS Twelve patients with MGMT-promotor methylated ndGBM (median, range: age 49.5, 26–69; KPS 90, 60–100) have been treated with a combination of TTFields plus CCNU/TMZ. The analysis included patients with complete resection (n=6), partial resection (n=5) as well as biopsy (n=1). CTCAE grade 3 hematotoxicities were observed in six patients, but were not considered to be related to the addition of TTFields to lomustine/TMZ. Medical device site reactions (low-grade skin reactions) were detected in five patients. At data cut-off, the analyzed patient population demonstrated a median PFS of 18.7 months, whereas the median OS was not yet reached. CONCLUSION The results of this analysis provide first indication that the combination of TTFields/lomustine/TMZ is safe and feasible. Moreover, the observed survival outcomes point to preliminary beneficial effects of the triple combination. Additional follow-up and a higher sample size is required and planned for further toxicity analysis and efficacy assessment of this combination.

scholarly journals RARE-39. COMBINATION OF TUMOR TREATING FIELDS (TTFIELDS) WITH LOMUSTINE (CCNU) AND TEMOZOLOMIDE (TMZ) IN NEWLY DIAGNOSED GLIOBLASTOMA (GBM) PATIENTS - A BI-CENTRIC ANALYSIS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi229-vi230
Author(s):  
Lazaros Lazaridis ◽  
Niklas Schäfer ◽  
Teresa Schmidt ◽  
Johannes Weller ◽  
Theophilos-Dimitrios Tzaridis ◽  
...  
Keyword(s):  
Promoter Methylation ◽  
Methylation Status ◽  
Case Series ◽  
Mgmt Promoter Methylation ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Skin Reactions ◽  
Term Survival ◽  
Mgmt Promoter ◽  
Newly Diagnosed Glioblastoma

Abstract BACKGROUND TTFields combined with TMZ chemotherapy demonstrated significantly improved PFS, OS and long-term survival in newly diagnosed glioblastoma (ndGBM) patients in the EF-14 trial; independent of MGMT-promoter methylation-status, age, grade of resection, and performance status. Recently, improved efficacy of lomustine/TMZ compared to TMZ monotherapy in ndGBM patients with MGMT-promotor methylation was reported in the CeTeG trial. As TTFields demonstrated a favorable safety profile as well as a high potential for being combined with other modalities and the encouraging results for methylated MGMT-promoter GBM patients in the CeTeG trial, there is a strong rationale for combining these treatment regimens. Here, we present a case series of patients receiving a combination of TTFields and lomustine/TMZ. METHODS Patients with ndGBM and MGMT-promoter methylation underwent combined therapy of TTFields plus lomustine/TMZ after surgery and radiochemotherapy. MGMT-promoter status was measured by pyrosequencing. Safety, feasibility, and first efficacy results are reported at data cut-off (April 26, 2019). RESULTS Sixteen patients with MGMT-promoter methylated ndGBM (median, range: age 50, 27–70; KPS 90, 60–100) have been treated with a combination of TTFields plus lomustine/TMZ. The analysis included patients with complete resection (n=7), partial resection (n=8), as well as biopsy (n=1). CTCAE grade 3 hematotoxicity was observed in seven patients (44%) but was unlikely related to the addition of TTFields to lomustine/TMZ. Medical device site reactions (low-grade skin reactions) were detected in six patients (38%). At data cut-off, the analyzed patient population demonstrated a median PFS of 20 months; the median OS was not yet reached. CONCLUSION The results of this analysis indicate that the combination of TTFields/lomustine/TMZ is safe and feasible. Moreover, the observed survival outcomes point to preliminary beneficial effects of the triple combination. Additional follow-up and increased sample size are required and planned for further safety and efficacy assessment of this treatment regimen.

scholarly journals NIMG-37. DELAYED PSEUDOPROGRESSION IN TWO PATIENTS UNDERGOING TTFIELDS TREATMENT FOR NEWLY DIAGNOSED GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii155-ii156
Author(s):  
Allison Lowman ◽  
Sarah Hurrell ◽  
Samuel Bobholz ◽  
Jennifer Connelly ◽  
Elizabeth Cochran ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Radiographic Progression ◽  
Methylation Status ◽  
Underlying Mechanism ◽  
Recurrent Glioblastoma ◽  
Newly Diagnosed ◽  
Methylguanine Dna Methyltransferase ◽  
Specific Effects ◽  
Newly Diagnosed Glioblastoma ◽  
Associated Risk Factors

Abstract PURPOSE Tumor treatment fields (TTFields) are approved by the FDA for newly diagnosed as well as recurrent glioblastoma (GBM). TTFields have been shown to extend survival by 4.9 months in newly diagnosed GBM, and a landmark overall survival rate of 13% at 5 years. However, the specific effects remain widely unknown, which has prevented widespread clinical use of this treatment. METHODS This case study examines two glioblastoma patients, IDH-1 wildtype, MGMT unmethylated, that received TTFields (Optune) in addition to maintenance temozolomide (TMZ) following radiation (RT). Both cases were followed using standard MR imaging. Second resections were performed due to radiographic progression of contrast enhancement. RESULTS Although imaging was concerning for tumor progression, pathology showed only treatment effect, ultimately leading to the diagnosis of pseudoprogression. Both patients fell outside the normal expected timeline for chemo-radiation induced pseudoprogression. Based on the pathology, both patients resumed treatment with TMZ/TTFields. One patient expired at 25 months and one is still alive. CONCLUSIONS Pathologic confirmation was essential for guiding further treatment and allowed patients to continue treatment that was effective despite contrary indications on imaging. These findings suggest that pathological confirmation should be strongly considered in patients receiving TMZ/TTFields who develop radiographic progression, potentially with a less invasive biopsy procedure. Future studies should look to characterize the underlying mechanism of interaction between TTFields/TMZ and quantify the prevalence, associated risk factors and whether there is a genotype more susceptible. Both patients reported here had O(6)-methylguanine-DNA methyltransferase (MGMT) unmethylated GBM, and while about 60% of glioblastomas are diagnosed likewise, it is possible that MGMT methylation status plays a role in TTFields response. Better characterization of this phenomenon will improve treatment guidance, potentially reducing unnecessary surgeries and the discontinuance of successful therapies.

scholarly journals Limited role for extended maintenance temozolomide for newly diagnosed glioblastoma

Neurology ◽  
2017 ◽  
Vol 88 (15) ◽  
pp. 1422-1430 ◽  
Author(s):  
Dorothee Gramatzki ◽  
Philipp Kickingereder ◽  
Bettina Hentschel ◽  
Jörg Felsberg ◽  
Ulrich Herrlinger ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Proportional Hazards Model ◽  
Methylation Status ◽  
Residual Tumor ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Karnofsky Performance Score ◽  
Newly Diagnosed ◽  
Clinical Patient ◽  
Newly Diagnosed Glioblastoma

Objective:To explore an association with survival of modifying the current standard of care for patients with newly diagnosed glioblastoma of surgery followed by radiotherapy plus concurrent and 6 cycles of maintenance temozolomide chemotherapy (TMZ/RT → TMZ) by extending TMZ beyond 6 cycles.Methods:The German Glioma Network cohort was screened for patients with newly diagnosed glioblastoma who received TMZ/RT → TMZ and completed ≥6 cycles of maintenance chemotherapy without progression. Associations of clinical patient characteristics, molecular markers, and residual tumor determined by magnetic resonance imaging after 6 cycles of TMZ with progression-free survival (PFS) and overall survival (OS) were analyzed with the log-rank test. Multivariate analyses using the Cox proportional hazards model were performed to assess associations of prolonged TMZ use with outcome.Results:Sixty-one of 142 identified patients received at least 7 maintenance TMZ cycles (median 11, range 7–20). Patients with extended maintenance TMZ treatment had better PFS (20.5 months, 95% confidence interval [CI] 17.7–23.3, vs 17.2 months, 95% CI 10.2–24.2, p = 0.035) but not OS (32.6 months, 95% CI 28.9–36.4, vs 33.2 months, 95% CI 25.3–41.0, p = 0.126). However, there was no significant association of prolonged TMZ chemotherapy with PFS (hazard ratio [HR] = 0.8, 95% CI 0.4–1.6, p = 0.559) or OS (HR = 1.6, 95% CI 0.8–3.3, p = 0.218) adjusted for age, extent of resection, Karnofsky performance score, presence of residual tumor, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, or isocitrate dehydrogenase (IDH) mutation status.Conclusion:These data may not support the practice of prolonging maintenance TMZ chemotherapy beyond 6 cycles.Classification of evidence:This study provides Class III evidence that in patients with newly diagnosed glioblastoma, prolonged TMZ chemotherapy does not significantly increase PFS or OS.

RADT-13. SPARE TRIAL: SCALP-SPARING RADIATION WITH CONCURRENT TEMOZOLOMIDE AND TUMOR TREATING FIELDS FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi43-vi44
Author(s):  
Ryan Miller ◽  
Andrew Song ◽  
Ayesha S Ali ◽  
Voichita Bar-Ad ◽  
Nina, L Martinez ◽  
...  
Keyword(s):  
Radiation Treatment ◽  
Methylation Status ◽  
Treatment Interruption ◽  
Newly Diagnosed ◽  
Entire Cohort ◽  
Tumor Treating Fields ◽  
Newly Diagnosed Glioblastoma ◽  
Prospective Trials ◽  
Dose Constraints ◽  
Topical Medications

Abstract INTRODUCTION Current adjuvant treatment for patients with newly diagnosed glioblastoma includes concurrent chemoradiation and maintenance temozolomide with Tumor Treating Fields (TTFields). We report our clinical trial evaluating feasibility and tolerability of scalp-sparing radiation with concurrent temozolomide and TTFields. METHODS Adult patients (age ≥ 18 years) with newly diagnosed glioblastoma with a KPS of ≥ 60 were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions) with temozolomide (75 mg/m2 daily) and TTFields (200 kHz). Maintenance therapy included temozolomide and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. The primary endpoint was safety and toxicity of tri-modality treatment within 30 days of completion of chemoradiation treatment. RESULTS Thirty patients were enrolled. Twenty were male and ten were female, with a median age of 58 years (range 19 to 77 years). Median follow-up was 10.8 months (range 1.6 to 21.3 months). Twenty (66.7%) patients had unmethylated MGMT promotor and ten (33.3%) patients had methylated promoter. Scalp dose constraints were achieved for all patients. Skin adverse events (erythema, dermatitis, irritation, folliculitis) were noted in 83.3% of patients, however, these were limited to Grade 1 or 2 events, which resolved spontaneously or with topical medications. No patient had radiation treatment interruption due to skin AEs. Other Grade 1 events included pruritus (33.3%), fatigue (30%), nausea (13.3%), headache (10%), dizziness (6.7%), and cognitive impairment (3.3%). Other Grade 2 events included headache (3.3%). The median PFS for the entire cohort was 9.1 months (at least 8.5 months, 95% confidence). The median PFS for patients with MGMT promoter methylation status was 11.4 months (at least 9.5 months, 95% confidence). Overall survival was not reached. CONCLUSIONS Concurrent TTFields with scalp-sparing chemoradiation is feasible treatment option with limited toxicity. Future randomized prospective trials are warranted to define therapeutic advantages of concurrent TTFields with chemoradiation.

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 Postoperative Prolonged Mechanical Ventilation in Patients With Newly Diagnosed Glioblastoma—An Unrecognized Prognostic Factor

2020 ◽  
Vol 10 ◽  
Author(s):  
Patrick Schuss ◽  
Felix Lehmann ◽  
Niklas Schäfer ◽  
Christian Bode ◽  
Elisa Scharnböck ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Prognostic Factors ◽  
Prognostic Factor ◽  
Functional Outcome ◽  
Prolonged Mechanical Ventilation ◽  
Methylation Status ◽  
Significant Prognostic Factor ◽  
Karnofsky Performance Score ◽  
Newly Diagnosed ◽  
Newly Diagnosed Glioblastoma

ObjectiveAlthough the treatment of glioblastoma patients is well established in neuro-oncological surgery, precious scarce data is available on patients with glioblastoma requiring postoperative prolonged mechanical ventilation (PMV). Therefore, the aim of the present study was to determine the influence of PMV on overall survival (OS) in patients with glioblastoma.MethodsPatients with newly diagnosed glioblastoma who had undergone surgical therapy and complete subsequent neuro-oncological treatment at the authors’ neuro-oncological center from January 2013 to December 2018 were selected and included in the further analysis. PMV was defined as mechanical ventilation for more than 24 h after surgery. Survival analyses were performed, including established prognostic factors such as age, Karnofsky performance score, MGMT-promoter methylation status and extent of resection.ResultsA total of 240 patients with newly diagnosed glioblastoma and subsequent surgical treatment were identified. 13 patients (5%) suffered from PMV during the treatment course of glioblastoma. All but one patient were successfully weaned from mechanical ventilation. Patients suffering from PMV achieved significantly less often favorable functional outcome after 3, 6, 9, and 12 months compared to patients without PMV. Multivariate analysis revealed PMV to constitute a significant prognostic factor for OS, independent of other prognostic factors (p<0.0001, OR 6.7, 95% CI 3.2–13.8).ConclusionsThe present study identifies PMV as significantly associated with impaired functional outcome and poor OS in patients suffering from newly diagnosed glioblastoma. These findings encourage further efforts to investigate/assess this prognostic factor in future studies.

NABTT 0306: A randomized phase II trial of EMD 121974 in conjunction with concomitant and adjuvant temozolomide with radiation therapy in patients with newly diagnosed glioblastoma multiforme (GBM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2001-2001 ◽  
Author(s):  
L. B. Nabors ◽  
T. Mikkelsen ◽  
T. Batchelor ◽  
G. Lesser ◽  
M. Rosenfeld ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Survival ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Methylation Status ◽  
Newly Diagnosed ◽  
Integrin Receptor ◽  
Randomized Phase Ii ◽  
Newly Diagnosed Glioblastoma ◽  
Dose Levels

2001 Background: EMD 121974 (cilengitide) is a selective integrin receptor inhibitor that is well tolerated and has demonstrated biological activity in patients with malignant glioma. The objectives of this phase II trial were to determine safety when combined with chemoradiation and estimate the overall survival for two different doses in newly diagnosed GBM. Methods: A total of 112 patients were accrued onto the trial through the NABTT CNS consortium. Cilengitide was administered by one-hour infusion twice a week with 18 patients treated in a safety run-in phase of 6 patients at the tested dose levels of 500 mg, 1000 mg, and 2000 mg. After safety completion, 94 patients were randomly assigned to either 500 mg or 2000 mg groups. To date, 55 out of 112 (49%) patients have died. Overall survival was estimated using all patients in this trial regardless of their treating dose. Results: The median age was 55 years old (range: 22–88) and the median KPS was 90 (range: 60–100). 86 out of the 112 (76.8%) had a craniotomy as their initial surgical procedure and 25 patients (22%) had a biopsy. There were no DLTs during the safety run-in phase. The estimated median survival time is 18.9 months (95% CI: 16.3 -30.0 months) for patients treated with RT+TMZ+EMD. The trial was closed to accrual on December 31, 2007. To date, 89 out of 112 patients were alive 12 months from their initial diagnosis. The overall survival at 12 months for all patients is 79.5% (95% CI: 71–87%). MGMT methylation status and survival based on dose levels received are not currently available. Conclusions: EMD 121974 (cilengitide) is well-tolerated when combined with standard chemoradiation (TMZ+RT) and may improve survival for patients newly diagnosed with GBM given the substantial differences between the estimated median survival and that seen in the EORTC study (Stupp, N Engl J Med, 2005). [Table: see text]

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