scholarly journals Laser Ablation of Newly Diagnosed Malignant Gliomas

Neurosurgery ◽  
2016 ◽  
Vol 79 (suppl_1) ◽  
pp. S17-S23 ◽  
Author(s):  
Michael E. Ivan ◽  
Alireza M. Mohammadi ◽  
Nicoleta De Deugd ◽  
Joshua Reyes ◽  
Gregor Rodriguez ◽  
...  
Keyword(s):  
Overall Survival ◽  
Minimally Invasive ◽  
Progression Free Survival ◽  
Small Sample ◽  
Invasive Technique ◽  
High Grade ◽  
Newly Diagnosed ◽  
Free Survival ◽  
High Grade Gliomas

Abstract BACKGROUND: Magnetic resonance-guided laser-interstitial thermotherapy (MR-LITT) is a minimally invasive technique that shows promise in neuro-oncology because of its superiority in delivering precise minimally invasive thermal energy with minimal collateral damage. OBJECTIVE: In this analysis, we investigate initial data on the use of MR-LITT in the treatment of newly diagnosed high-grade gliomas. METHODS: With the use of the PubMed, OVID, and Google-scholar database systems, a comprehensive search of the English literature was performed. Eighty-five articles were identified plus 1 that is pending publication. Four articles were accounted for in this review, including 25 patients with newly diagnosed high-grade gliomas who underwent MR-LITT treatment. We evaluated safety, progression-free survival, and overall survival. RESULTS: Twenty-five patients with a mean age of 53.8 years underwent LITT treatments. On average, 82.9% of the pretreatment lesion volume was ablated. The average tumor volume treated was 16.5 cm3. The mean follow-up time was 7.6 months. Median overall survival was found to be 14.2 months (range 0.1-23 months). The median progression-free survival was 5.1 months (range 2.4-23 months); however, these data are limited by the relatively short follow-up of the patients reviewed and small sample size of only 25 patients. There was 1 (3.4%) major perioperative complication, which was a central nervous system infection. CONCLUSION: MR-LITT is a promising technology for the treatment of small, yet difficult-to-treat newly diagnosed high-grade gliomas. This study demonstrates that MR-LITT is safe, and future randomized studies are needed to evaluate its role as a treatment adjunct for newly diagnosed high-grade gliomas.

Disease-Management of Low- and Intermediate-1 Risk Myelodysplastic Syndromes: Report on 800 Newly Diagnosed MDS Patients From the European LeukemiaNet MDS Registry

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2917-2917 ◽  
Author(s):  
Louise de Swart ◽  
Alex Smith ◽  
Pierre Fenaux ◽  
Argyris Symeonidis ◽  
Eva Hellström-Lindberg ◽  
...  
Keyword(s):  
Overall Survival ◽  
Disease Management ◽  
Serum Ferritin ◽  
Research Funding ◽  
Iron Chelation ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival ◽  
The Mean

Abstract Abstract 2917 Background: The European LeukemiaNet MDS (EUMDS) registry is designed to collect information about the demographics and disease-management of newly diagnosed low-risk and intermediate-1 risk MDS patients. From April 2008 until July 2010, 828 patients have been registered in eleven participating countries through a web-based reporting system. Objectives: This report describes the disease-management of the first 800 registered patients, including transfusion-related issues like secondary iron overload and its treatment. Results: 159 of 800 patients (20%) started MDS specific treatment within three months before registration; this percentage increased to 50% at 18 months of follow-up. Most patients received erythroid-stimulating agents (ESA), like erythropoietin (Table 1). In patients with a clinical indication for ESA, the percentage of transfusion-independency was similar to the transfusion-independent group without indication for ESA at 18 months of follow-up (Table 1). Overall, 27% of the patients received blood transfusions at registration. This percentage remained stable during follow-up, probably due to the therapeutic effect of ESA (Table 1). The number of units transfused, per 6 months, in these patients increased from 5 to 13 units at 18 months of follow-up, with a mean pre-transfusion Hb level of 7.6 g/dL. The serum ferritin levels of the transfusion-dependent patients at registration were available in 159 patients. The serum ferritin level at registration was ≥2000 μg/L in 4% of the patients who received a mean number of 10 units (SD 7). This increased to 28% of the patients who received a mean number of 20 units (SD 11) at 18 months of follow-up. The percentage of patients on iron chelation therapy increased from 1% to 9% during follow-up (Table 1). In these patients the mean serum ferritin levels remained stable: 1913 μg/L (SD 1183) at registration and 1626 μg/L (SD 1232) at 18 months of follow-up. In contrast, transfusion-dependent patients not treated with iron chelation or ESA had increasing ferritin levels, with a mean ferritin of 630 μg/L (SD 597) at registration and 1586 μg/L (SD 1017) at 18 months of follow-up. 37 patients (5%) progressed to high-risk MDS or acute myeloblastic leukemia at a median of 155 days from registration. 62 patients (8%) have died within a median of 269 days from registration, 32 deaths were MDS related. The overall survival was 93% at 18 months of follow-up, with a progression-free survival of 90%. Differences in overall survival between transfusion-independent and transfusion-dependent patients were significant: 97% versus 85%, respectively (p<0.0001; Table 2). In the multivariate analysis transfusion-dependency, ferritin levels and IPSS score predicted survival (Table 2). The IPSS score had a significant prognostic impact on overall survival and progression-free survival in contrast to the WHO classification (Data not shown). Conclusions: Despite a high transfusion load the mean serum ferritin levels remained stable during treatment with iron chelation. Transfusion-dependent patients had a worse overall survival and progression-free survival with higher ferritin levels and higher IPSS score as compared to transfusion-independent patients. This report demonstrates the importance of detailed disease-management in low- and intermediate-1 risk MDS patients. Disclosures: Fenaux: Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen Cilag: Honoraria, Research Funding; ROCHE: Honoraria, Research Funding; AMGEN: Honoraria, Research Funding; GSK: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Cephalon: Honoraria, Research Funding. Bowen:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AMGEN: Honoraria; Celgene: Honoraria, Research Funding; Chugai: Honoraria, Research Funding.

Analysis of 179 Patients with Newly Diagnosed Multiple Myeloma (MM) Treated with Novel Agents Followed by Autologous Stem Cell Transplantation (ASCT): a Retrospective Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1343-1343
Author(s):  
Joyce Habib ◽  
Neil Dunavin ◽  
Gary Phillips ◽  
Patrick Elder ◽  
Meaghan Tranovich ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Risk ◽  
Research Funding ◽  
Progression Free Survival ◽  
Novel Agents ◽  
Genetic Profile ◽  
Newly Diagnosed ◽  
Free Survival

Abstract Abstract 1343 Background: Multiple myeloma (MM) is the second most common hematological malignancy in the United States with an estimated 20,580 new cases in 2009. Over the past decade, the introduction of novel agents (thalidomide, lenalidomide and bortezomib) have played a pivotal role in improving response rates, duration of response, overall survival (OS) and quality of life. In this study we describe a single center experience with novel agents used for induction followed by high dose chemotherapy (HDT) and first autologous stem cell transplant (ASCT) in patients with MM. Method: A retrospective review of the medical records of 179 newly diagnosed patients with MM seen between October 2006 and December 2009 at The Ohio State University was performed. All patients received novel therapy containing thalidomide, bortezomib or lenalidomide as part of an induction regimen followed by ASCT. All patients received melphalan 140mg/m2 or 200mg/m2 as preparative regimen. Kaplan-Meier estimates were used to plot progression free survival and overall survival. Results: Of the 181 patients seen, 2 were excluded because they did not receive a novel agent as part of induction treatment. Of the 179 patients analyzed, median age was 56.8 years (29-80) with 30% of patients older than 60 years. African American represented 19%. Fifty-nine percent were male, 80% had Durie-Salmon (DS) stage III while 25%, 28%, 18% represented International prognostic score (IPS) stage I, II, and III respectively with 27% unknown. Median comorbidity index score was 2 (2-7) and median Karnofsky performance score (KPS) was 90% (70-100). Thirty percent had high risk genetic profile, and 73% received one line of treatment before ASCT. The median time from diagnosis to ASCT was 8.33 months (4-58). The overall response rate (ORR) prior to transplant was 84% (9% complete (CR), 29% very good partial (VGPR), and 46% partial (PR)). The ORR post ASCT was 89% (CR 45%, VGPR 22%, PR 21%). Non relapse mortality was 1% and 3% at 100 days and 1 year respectively. At a median follow up of 31 months (7-90), 69 patients (38%) had relapsed. Median progression free survival (PFS) was 29 months with 1 and 3 years PFS of 79.3% and 61.5% respectively (Fig. 1). The OS was not reached. One and 3 years OS were 93% and 88% respectively (Fig. 1). Univariate analysis showed that time to transplant > 12 months was associated with poor outcome and decreased overall survival (HR 3.30, p = 0.008). High risk genetic profile was also found to be associated with decreased overall survival although this was not statistically significant (HR 2.31, p = 0.070). Multivariate analysis found that only time to transplant > 12 months was an independent predictor of decreased OS. Significant predictors for disease progression were high risk genetic profile and time to transplant > 12 months in patients receiving 2 or more treatments before ASCT. Conclusion: Induction with novel agents followed by HDT and ASCT improves CR rate, in our case from 9% to 45%. Median PFS (29 months) was comparable to other published data. OS was not been reached after a median follow up of 31 months. Predictors of progression include high risk genetic profile and time to transplant > 12 months. The only significant predictor for survival was time to transplant. Our study suggests that an early transplant may improve OS and PFS. An extended analysis will be presented at the meeting. Disclosures: Phillips: NCI/NIH: Research Funding; NCCM Grant: Research Funding; ARRA RC2 Grant: Research Funding. Byrd:Genzyme Corporation: Research Funding.

A Randomized Clinical Trial of Lenalidomide and Dexamethasone with and without Autologous Stem Cell Transplant in Patients with Newly Diagnosed Multiple Myeloma: Interim Study Results,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4142-4142 ◽  
Author(s):  
Lijun Dai ◽  
Amy O'Sullivan ◽  
Ryan Kennedy ◽  
Mohammad Abbas ◽  
Yongli Shuai ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Low Dose ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival

Abstract Abstract 4142 Introduction: High dose chemotherapy combined with autologous stem cell transplantation (ASCT) as opposed to conventional chemotherapy improved progression free survival (PFS) and overall survival (OS) in multiple myeloma (MM) and is currently the standard of care for newly diagnosed MM patients less than 65 years old. Over the last decade, novel agents such as lenalidomide or bortezomib have dramatically improved MM outcomes with similar response rates as ASCT and the role of upfront ASCT has become more controversial. Therefore the goal of this randomized clinical trial is to determine the role of upfront ASCT in newly diagnosed myeloma patients receiving novel agent lenalidomide and low-dose dexamethasone induction. Methods: Patients aged ≥18 years with newly confirmed, measurable MM in stage 2 and 3 (Salmon Durie) and meeting CRAB criteria were enrolled. Patients were randomized to transplant (Arm A) or to non-transplant (Arm B). Patients in Arm A received 4 cycles of lenalidomide (25mg days 1 – 21) plus low-dose dexamethasone (40mg days 1,8,15,22) followed by ASCT conditioned with 200 mg/m2 melphalan (LD+ASCT); Arm B patients received 8 cycles of lenalidomide plus low-dose dexamethasone (LD alone). Both arms received stem cell collection after 4 cycles of therapy if patients achieved at least a partial remission (PR). Patients with stable disease (SD) or progressive disease (PD) went off study. The primary objective was to compare best response. The secondary endpoints included duration of response (DOR), progression free survival (PFS), overall survival (OS) and evaluation of secondary malignancies in both arms. Results: From February 2008 to May 2011, 44 patients with newly diagnosed MM were randomized. The patient characteristics were as follow: median age of the patients was 61.7 years (range 48∼75), 45.5% female and 55.5% male patients, ISS stage I 31%, II 51% and III 18%. 40 patients were eligible for evaluation and 20 patients were randomized to Arm A or Arm B, respectively. The data were analyzed according to latest IMWG response criteria (Blood. 2011 May 5;117(18):4691–5). In an intention to treat analysis, patients in Arm A (LD + ASCT), achieved a 100% Overall Response Rate (ORR) with 40% PR (n=8) and 60% Very Good Partial Response (VGPR) (n=12). In Arm B (LD only) the ORR was 75% (n=15), including 15% CR (n=3), 35% VGPR (n=7), 25% PR (n=5), 20% SD (n=4) and 5% PD (n=1). The ORR was significantly superior in the LD+ASCT group compared to LD alone (p=0.047). After a median follow-up of 25.3 months, 17 patients have PD (8 in LD+ASCT and 9 in LD alone), 6 have died (1 in LD+ASCT and 5 in LD alone). DOR, PFS and OS were not significantly different in both groups. OS showed a trend to be superior in patients treated with LD+ASCT (p=0.08). (Table 1). One patient in the LD+ASCT arm developed MDS 13 months after start of therapy. Conclusion: Our interim analysis of an ongoing clinical study suggests that treatment of newly diagnosed MM patients with lenalidomide plus low-dose dexamethasone induction followed by upfront ASCT resulted in significantly improved ORR. There was no difference in terms of DOR or PFS with a trend of superior OS in the LD+ASCT group. The study requires careful interpretation based on the low patient number and relatively short follow up, but supports the continued role of upfront consolidative ASCT in newly diagnosed MM patients. The incidence of secondary malignancy was low with the development of 1 MDS. Updated data on response and overall survival will be available at the time of presentation. Disclosures: Roodman: Amgen: Consultancy; Millennium Pharmaceuticals: Consultancy. Raptis:Millennium: Speakers Bureau; Celgene Corp: Speakers Bureau; Eisai: Speakers Bureau. Lentzsch:Celgene Corp: Consultancy, Research Funding; Onyx: Consultancy; Genzyme: Consultancy; prIME Oncology: Honoraria; Imedex: Honoraria; Clinical Care Options: Honoraria.

Comparison of 5-aminolevulinic acid and sodium fluorescein for intraoperative tumor visualization in patients with high-grade gliomas: a single-center retrospective study

2020 ◽  
Vol 133 (5) ◽  
pp. 1324-1331 ◽  
Author(s):  
Rasmus W. Hansen ◽  
Christian B. Pedersen ◽  
Bo Halle ◽  
Anders R. Korshoej ◽  
Mette K. Schulz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Volume ◽  
Fluorescent Dyes ◽  
Aminolevulinic Acid ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Sodium Fluorescein ◽  
High Grade ◽  
Free Survival ◽  
High Grade Gliomas

OBJECTIVEMaximal safe resection is an important surgical goal in the treatment for high-grade gliomas. Fluorescent dyes help the surgeon to distinguish malignant tissue from healthy. The aims of this study were 1) to compare the 2 fluorescent dyes 5-aminolevulinic acid (5-ALA) and sodium fluorescein (fluorescein) regarding extent of resection, progression-free survival, and overall survival; and 2) to assess the influence of other risk factors on clinical outcome and screen for potential disadvantages of the dyes.METHODSA total of 209 patients with high-grade gliomas were included in this retrospective study. Resections were performed in the period from 2012 to 2017 using 5-ALA or fluorescein. Extent of resection was assessed as the difference in tumor volume between early postoperative and preoperative MRI studies. Tumor progression–free survival and overall survival were analyzed using an adjusted Cox proportional hazards model.RESULTSOne hundred fifty-eight patients were operated on with 5-ALA and 51 with fluorescein. The median duration of follow-up was 46.7 and 21.2 months, respectively. Covariables were evenly distributed. There was no statistically significant difference in volumetrically assessed median extent of resection (96.9% for 5-ALA vs 97.4% for fluorescein, p = 0.46) or the percentage of patients with residual tumor volume less than 0.175 cm3 (29.5% for 5-ALA vs 36.2% for fluorescein, p = 0.39). The median overall survival was 14.8 months for the 5-ALA group and 19.7 months for the fluorescein group (p = 0.06). The median adjusted progression-free survival was 8.7 months for the 5-ALA group and 9.2 months for the fluorescein group (p = 0.03).CONCLUSIONSFluorescein can be used as a viable alternative to 5-ALA for intraoperative fluorescent guidance in brain tumor surgery. Comparative, prospective, and randomized studies are much needed.

Prognostic factors of overall survival after laser interstitial thermal therapy in patients with glioblastoma

2014 ◽  
Vol 3 (2) ◽  
Author(s):  
Symeon Missios ◽  
Jason L. Schroeder ◽  
Gene H. Barnett ◽  
Alireza M. Mohammadi
Keyword(s):  
Overall Survival ◽  
Cleveland Clinic ◽  
Progression Free Survival ◽  
Thermal Therapy ◽  
Invasive Technique ◽  
Free Survival ◽  
Laser Interstitial Thermal Therapy ◽  
Effective Manner ◽  
Improve Patient

AbstractBackground:Laser interstitial thermal therapy (LITT) is a minimally invasive technique for treating intracranial tumors percutaneously. Controlled thermal damage to the tumor may offer an adjunct to the treatment of glioblastoma multiforme (GBM) especially in deep-seated locations. We report our series of patients with GBM treated with LITT.Methods:Eleven consecutive patients with GBM who underwent LITT at the Cleveland Clinic using the NeuroBlateResults:LITT was delivered as upfront treatment in six cases and delivered as salvage in five cases. After 26.2 months of follow-up, 73% of cases demonstrated progression and 54.5% died. The median overall survival (OS) for the cohort was 8.4 months. Median progression free survival (PFS) was 6.1 months. A tendency towards improved overall survival was discovered in patients who had near complete coverage of tumor by blue and yellow TDT-lines.Conclusions:LITT can be used in a safe and effective manner for the treatment of patients with difficult to access GBM. Improved coverage of the tumor by the TDT-treatment lines has a tendency to improve patient overall survival.

scholarly journals Liposomal Vincristine (Marqibo) Combined with Hyper-Cmad As Frontline Therapy for Patients with Acute Lymphoblastic Leukemia: A Result of a Phase II Clinical Trial

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3720-3720
Author(s):  
Koji Sasaki ◽  
Elias Jabbour ◽  
Deborah A Thomas ◽  
Maria R. Khouri ◽  
Musa Yilmaz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Progression Free Survival ◽  
Salvage Chemotherapy ◽  
Time Interval ◽  
Newly Diagnosed ◽  
Free Survival

Abstract Background: Liposomal vincristine has been approved as salvage chemotherapy for patients with relapsed/refractory acute lymphoblastic leukemia (ALL). Replacement of regular vincristine with liposomal vincristine might lead to improve outcome with reduced neurotoxicity in patients with newly diagnosed ALL. Methods: Patients ≥18 years with newly-diagnosed B-cell ALL were eligible for the clinical trial consisting of hyper-CMAD (cyclophosphamide 300 mg/m2 IV every 12 hours on Days 1-3; liposomal vincristine 2 mg/m2 IV on Day 1 and day 8; doxorubicin 50 mg/m2 IV on Day 4; dexamethasone 40 mg IV daily on Days 1-4 and Days 11-14) (odd cycles 1, 3, 5, 7) alternating with high-dose methotrexate 1000 mg/m2 IV on Day 1, and cytarabine 3 gm/m2 IV every 12 hours on Days 2 and 3 (even cycles 2, 4, 6, 8). Rituximab 375 mg/m2 IV on Days 1 and 8 for courses 1-4 was administered in CD-20 positive ALL. TKI (imatinib or dasatinib) were concomitantly administered in patients with Philadelphia chromosome positive (Ph+) ALL. Overall survival (OS) was defined as time interval from the start date of hyper-CMAD to the date of death. Progression-free survival (PFS) was defined as time interval from the start date of hyper-CMAD to the date of relapse or death, whichever comes first. Results: Twenty-seven patients have been treated so far. Baseline patient characteristics are described in table 1. Median age is 53 years (range 23-80). Eleven patients (41%) had CD-20 positive ALL, and 17 (63%) had Ph+ ALL. Median follow-up is 12 months (3-22) with a median of 4 cycles (1-8) administered Of 17 patients with Ph+ ALL, 15 patients were received additional dasatinib and 2 imatinib. Twenty-six (96%) achieved complete response (CR). Early death was observed in 1 patient (4%) with Ph+ ALL. Of the 26 patients evaluable for response, 22 (100%) achieved CCyR (3 patients, diploid at start; 1 patient, not performed), and 23 (88%) achieved negative MRD by multicolor flow cytometry. Of the 16 evaluable Ph-positive patients, MMR was observed in 15 (94%) and CMR in 10 (63%). Three patients in CR1 underwent allogeneic stem cell transplantation (ASCT). At the last follow-up, 23 (85%) patients are alive. Four (15%) patients died: 1 from sepsis on C1D10; 1 from unknown cause on C1D135; 1 from post-transplant complications; and 1 from disease progression at the third salvage chemotherapy. Median time to platelet and neutrophil recovery for cycle 1 was 24 and 19 days, respectively. To date, 3 patients relapsed; 1 patient with t(4;11) relapsed at C5D36; 1 Ph-positive patient relapsed post C8 with no maintenance therapy; 1 patient with positive MRD 2 months prior to morphologic relapse while on maintenance therapy C10D32. At the last follow-up, 23 (85%) patients are alive. Four (15%) patients died: 1 from sepsis on C1D10; 1 from unknown cause on C1D135; 1 from post-transplant complications; and 1 from relapse and disease progression at the third salvage chemotherapy. The 1-year PFS and OS rates were 77% and 87%, respectively. Conclusions: The combination ofliposomal vincristine withHyper-CMAD is safe and effective with high response rates in patients with newly diagnosed ALL. Table 1. Patient characteristic and outcome N (%)/ Median [range] N= 27 Age (yrs) 53 (23-80) Age ≥ 60 10 (37) Male 12 (44) PS 2-3 2 (7) WBC (x 109/L) 17.1 (1.4-372.1) CNS disease 6 (22) CD20 positivity 11 (41) Cytogenetic Abnormality, No. (%) Diploid 3 (11) Philadelphia chromosome 17 (63) Hypodiploid 2 (7) Hyperdiploid 1 (4) t(4;11) 3 (11) Misc 1 (4) Overall response, No. (%) CR 26/27 (96) Early death 1/27 (4) CCyR 22/22 (100) MRD by Flow 23/26 (88) MMR:BCR/ABL 15/16 (94) CMR:BCR/ABL 10/16 (63) Figure 1. Progression-free survival and overall survival Figure 1. Progression-free survival and overall survival Disclosures Chahoud: American Society of Hematology (ASH): Other: 2015 HONORS Award recipient. DiNardo:Novartis: Research Funding. Pemmaraju:Stemline: Research Funding; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; LFB: Consultancy, Honoraria. Cortes:BMS: Consultancy, Research Funding; Teva: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; ARIAD Pharmaceuticals Inc.: Consultancy, Research Funding. O'Brien:Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding.

Irinotecan and bevacizumab in progressive primary brain tumors: The Cleveland Clinic experience

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2077-2077 ◽  
Author(s):  
T. Kang ◽  
T. Jin ◽  
D. Peereboom
Keyword(s):  
Overall Survival ◽  
Cleveland Clinic ◽  
Progression Free Survival ◽  
Median Number ◽  
High Grade ◽  
Free Survival ◽  
Intention To Treat ◽  
Kaplan Meier ◽  
High Grade Gliomas ◽  
Chemotherapy Patients

2077 Background: High-grade gliomas are generally resistant to modern chemotherapy. In the case of glioblastoma multiforme, median overall survival has been less than 12 months and progression free survival of less than 4 months. For patients with recurrent GBMs, the 6 month progression free survival is 15–20%. The combination of irinotecan and bevacizumab is an active regimen in the treatment of this disease. Herein we report the experiences with this regimen at our institution with the objective of identifying a therapy with a better outcome than historical results. Methods: Single institutional, retrospective review of 27 patients with recurrent or progressive high grade gliomas treated at the Cleveland Clinic Brain Tumor Institute from 7/2005 through 10/2006. Patients had progressed on at least one prior chemotherapy. Patients with prior irinotecan or bevacizumab were excluded. Patients were analyzed on an intention-to-treat basis, and outcomes estimated by the Kaplan-Meier method. Results: The median age of the group was 46 years (range 5–69). The median number of prior therapies was 2 (range 1–10). Twenty of 27 patients have progressed (74%), and 11 of 27 patients have died (41%). Kaplan-Meier estimates for outcomes are summarized in the table . Progression-free survival at 6 months is 46 %, with median of 5.1 months. Overall survival at 6 months is 84%, with median of 12.6 months. In 7 patients, treatment was terminated early prior to progression. Significant toxicities include: one patient who developed hematuria, one patient with deep venous thrombosis and one patient who experienced intracranial hemorrhage. Conclusions: Our experience suggests that the combination of irinotecan and bevacizumab improves the 6-month progression-free survival when compared to historical figures. The rate of severe toxicities is consistent with prior reports and mandates careful selection of patients. Further randomized, phase 3 studies should be done to validate these results. [Table: see text] No significant financial relationships to disclose.

scholarly journals Mebendazole and temozolomide in patients with newly diagnosed high-grade gliomas: Results of a phase 1 clinical trial

2020 ◽  
Author(s):  
Gary L Gallia ◽  
Matthias Holdhoff ◽  
Henry Brem ◽  
Avadhut D Joshi ◽  
Christine L Hann ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Plasma Levels ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
High Grade ◽  
Newly Diagnosed ◽  
Kaplan Meier ◽  
High Grade Gliomas ◽  
Expansion Cohort

Abstract Background Mebendazole is an anthelmintic drug introduced for human use in 1971 that extends survival in preclinical models of glioblastoma and other brain cancers. Methods A single center dose escalation and safety study of mebendazole in 24 patients with newly diagnosed high-grade gliomas (HGG) in combination with temozolomide was conducted. Patients received mebendazole in combination with adjuvant temozolomide after completing concurrent radiation plus temozolomide. Dose escalation levels were 25, 50, 100 and 200 mg/kg/day of oral mebendazole. A 15-patient expansion cohort was conducted at the maximum tolerated dose of 200 mg/kg/day. Trough plasma levels of mebendazole were measured at 4, 8 and 16 weeks. Results Twenty-four patients (18 glioblastoma, 6 anaplastic astrocytoma) were enrolled with median age of 49.9 years. Four patients (at 200 mg/kg) developed elevated grade 3 ALT and/or AST after one month, which reversed with lower dosing or discontinuation. Plasma levels of mebendazole were variable but generally increased with dose. Kaplan Meier analysis showed a 21-month median survival with 43% of patients alive at two years and 25% at 3 and 4 years. Median progression free survival (PFS) from the date of diagnosis for 17 patients taking more than one month of mebendazole was 13.1 months (95% Confidence Interval: 8.8 to 14.6 months) but for seven patients who received less than one month of mebendazole PFS was 9.2 months (95% CI: 5.8 -13.0 months). Conclusion Mebendazole at doses up to 200 mg/kg demonstrated long-term safety and acceptable toxicity. Further studies are needed to determine mebendazole’s efficacy in patients with HGG.

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