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 Prospective Prediction of Clinical Drug Response in High Grade Gliomas Using an Ex Vivo 3D Cell Culture Assay

2021 ◽  
Author(s):  
Stephen Shuford ◽  
Lindsay Lipinski ◽  
Ajay Abad ◽  
Ashley M Smith ◽  
Melissa Rayner ◽  
...  
Keyword(s):  
Cell Culture ◽  
Overall Survival ◽  
Clinical Response ◽  
Case Studies ◽  
Drug Response ◽  
Ex Vivo ◽  
3D Cell Culture ◽  
High Grade ◽  
Cell Culture Assay ◽  
Clinical Drug

Abstract Background Clinical outcomes in high-grade glioma (HGG) have remained relatively unchanged over the last three decades with only modest increases in overall survival. Despite the validation of biomarkers to classify treatment response, most newly diagnosed (ND) patients receive the same treatment regimen. This study aimed to determine whether a prospective functional assay that provides a direct, live tumor cell-based drug response prediction specific for each patient could accurately predict clinical drug response prior to treatment. Methods A modified 3D cell culture assay was validated to establish baseline parameters including drug concentrations, timing, and reproducibility. Live tumor tissue from HGG patients were tested in the assay to establish response parameters. Clinical correlation was determined between prospective ex vivo response and clinical response in ND HGG patients enrolled in 3D-PREDICT (ClinicalTrials.gov Identifier: NCT03561207). Clinical case studies were examined for relapsed HGG patients enrolled on 3D-PREDICT, prospectively assayed for ex vivo drug response, and monitored for follow-up. Results Absent biomarker stratification, the test accurately predicted clinical response/non-response to temozolomide in 17/20 (85%, p = 0.007) ND patients within 7 days of their surgery, prior to treatment initiation. Test-predicted responders had a median overall survival post-surgery of 11.6 months compared to 5.9 months for test-predicted non-responders (p = 0.0376). Case studies provided examples of the clinical utility of the assay predictions and their impact upon treatment decisions resulting in positive clinical outcomes. Conclusion This study both validates the developed assay analytically and clinically and provides case studies of its implementation in clinical practice.

scholarly journals OS12.2 Targeting epigenetic pathways in the treatment of recurrent high-grade glioma

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii22-iii22
Author(s):  
A Hau ◽  
L Houben ◽  
E Klein ◽  
A Oudin ◽  
D Stieber ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Drug Response ◽  
High Grade Glioma ◽  
Differential Sensitivity ◽  
Targeted Sequencing ◽  
Patient Specific ◽  
Comparative Genomic ◽  
High Grade ◽  
Evolutionary Trajectory ◽  
Tumor Organoids

Abstract BACKGROUND High grade glioma (HGG) patients develop resistance to standard treatment leading to disease progression and limited life expectancy. Advances in the molecular characterisation of treatment-naïve HGGs based on next-generation sequencing and DNA methylation analyses have led to a better delineation of HGG subtypes and the identification of distinct genomic abnormalities. Furthermore, using large patient cohorts of longitudinal tumor samples, comprehensive genomic profiling studies emerged to investigate therapy-associated evolution of gliomas. All together, those studies point out the need for personalised treatment strategies, where applied drugs will be adapted to the unique patient-specific genetic abnormalities. MATERIAL AND METHODS We collected fresh samples of more than 800 brain tumors containing almost 300 glioma specimen with approximately 100 longitudinal samples of initial and recurrent tumors from 43 matched patients. By now, we have successfully established 34 patient-derived orthotopic xenografts (PDOXs) in mice. We performed comprehensive molecular profiling using array comparative genomic hybridisation, DNA methylation analysis and targeted DNA sequencing on patient specimen and their derivatives such as 3D tumor organoids and PDOXs. The custom-design sequencing panel comprises 234 genes that reflect both established genetic identifiers for individual glioma subtype classification and novel genes encoding mainly epigenetic effector genes. Based on patient-derived material we carried out drug response screening on 3D tumor organoids using a compound library matching the majority of genes that were assessed by targeted sequencing. RESULTS We succeeded in generating a live biobank of HGG patient-derived xenografts and 3D organoids that neatly recapitulates the mutational spectrum including structural DNA variation and methylation-based subtypes of gliomas. A highlight is the generation of 19 PDOXs of paired initial and relapse HGGs from a total of 9 glioma patients. A detailed analysis of the paired longitudinal samples indicated that PDOX models closely recapitulate the evolutionary trajectory of the parental tumors. Targeted sequencing of longitudinal HGG PDOXs suggests that relapse tumors accumulate somatic mutations in epigenetic effectors compared with the Initial. Differential drug responses between initial and relapse tumors were observed after screening of in vitro 3D tumor organoids. CONCLUSION Response assessment of naïve initial gliomas and recurrences provides crucial information on the differential sensitivity between initial and relapsed HGGs and offers novel personalised therapeutic options in the relapse setting. Furthermore, in depth correlation of the profiled somatic molecular landscape with drug response will enable pharmacogenomic predictions of potential inhibitors in the clinical setting.

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 QOLP-23. PHASE II RANDOMISED PLACEBO-CONTROLLED DOUBLE-BLIND STUDY OF ACETAZOLAMIDE VERSUS PLACEBO FOR CEREBRAL OEDEMA IN RECURRENT AND/OR PROGRESSIVE HIGH-GRADE GLIOMA REQUIRING TREATMENT WITH DEXAMETHASONE

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii179-ii180
Author(s):  
Meera Agar ◽  
Anna Nowak ◽  
Elizabeth Hovey ◽  
Elizabeth Barnes ◽  
John Simes ◽  
...  
Keyword(s):  
Adverse Events ◽  
Dose Reduction ◽  
Primary Endpoint ◽  
Performance Status ◽  
Case Series ◽  
High Grade Glioma ◽  
Double Blind Study ◽  
High Grade ◽  
Serious Adverse Events ◽  
Double Blind

Abstract INTRODUCTION Symptoms of raised intracranial pressure (ICP) in recurrent or progressive high-grade glioma (HGG) generally require corticosteroid treatment, often causing toxicity with variable effects on reversing ICP symptoms. Acetazolamide reduces ICP in other clinical settings including case series in glioma. AIM To explore whether addition of oral acetazolamide enables safe dexamethasone dose reduction in management of raised ICP in recurrent and/or progressive HGG. METHODS Participants had recurrent, progressive and/or persistent residual HGG requiring recommencement of dexamethasone, dose increase or dexamethasone dependency; prior/current bevacizumab was an exclusion. Eligible participants were randomised 1:1 to acetazolamide 250mg twice daily or placebo for 8 weeks. Standardised protocols were used for dexamethasone dose changes in both arms, with planned dose decrease from day 5 once ICP symptoms were stable. The primary endpoint was a composite of dexamethasone dose reduction and stability of performance status. Secondary endpoints included toxicity and feasibility (accrual and compliance). RESULTS Thirty participants of a planned sample of 84 were enrolled (mean age 58 y (32-89)) from 7 Australian sites. The mean baseline dexamethasone dose was 6.2mg (4-16mg). Mean duration on treatment was 38 days (4-57) in placebo group and 31 days (3-60) in acetazolamide group, with 9 participants (30%) completing all study treatment (6 placebo, 3 acetazolamide). Study withdrawal was due to adverse events (n=6 (1 placebo, 5 acetazolamide)) and disease progression (n=6 (3 per arm)). Four participants (13%) (2 per arm) were stable responders meeting the primary endpoint criteria (≥50% corticosteroid dose reduction from baseline by 28 days maintained for 7 days, and no deterioration in performance status). Ten participants experienced a total of 13 serious adverse events (acetazolamide arm: 5 participants (33%), 6 events, 2 related). DISCUSSION The addition of acetazolamide did not facilitate dexamethasone reduction. The study closed early due to poor accrual and increasing availability of bevacizumab.

Comparison Between 18F-Dopa and 18F-Fet PET/CT in Patients with Suspicious Recurrent High Grade Glioma: A Literature Review and Our Experience

2019 ◽  
Vol 12 (3) ◽  
pp. 220-228 ◽  
Author(s):  
Laura Evangelista ◽  
Lea Cuppari ◽  
Luisa Bellu ◽  
Daniele Bertin ◽  
Mario Caccese ◽  
...  
Keyword(s):  
Case Series ◽  
High Grade Glioma ◽  
High Grade ◽  
True Negative ◽  
Fet Pet ◽  
Positron Emission ◽  
Pet Ct ◽  
Magnetic Resonance Imaging Mri ◽  
Definition Of ◽  
Sensitivity Specificity

Purpose: The aims of the present study were to: 1- critically assess the utility of L-3,4- dihydroxy-6-18Ffluoro-phenyl-alanine (18F-DOPA) and O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) Positron Emission Tomography (PET)/Computed Tomography (CT) in patients with high grade glioma (HGG) and 2- describe the results of 18F-DOPA and 18F-FET PET/CT in a case series of patients with recurrent HGG. Methods: We searched for studies using the following databases: PubMed, Web of Science and Scopus. The search terms were: glioma OR brain neoplasm and DOPA OR DOPA PET OR DOPA PET/CT and FET OR FET PET OR FET PET/CT. From a mono-institutional database, we retrospectively analyzed the 18F-DOPA and 18F-FET PET/CT of 29 patients (age: 56 ± 12 years) with suspicious for recurrent HGG. All patients underwent 18F-DOPA or 18F-FET PET/CT for a multidisciplinary decision. The final definition of recurrence was made by magnetic resonance imaging (MRI) and/or multidisciplinary decision, mainly based on the clinical data. Results: Fifty-one articles were found, of which 49 were discarded, therefore 2 studies were finally selected. In both the studies, 18F-DOPA and 18F-FET as exchangeable in clinical practice particularly for HGG patients. From our institutional experience, in 29 patients, we found that sensitivity, specificity and accuracy of 18F-DOPA PET/CT in HGG were 100% (95% confidence interval- 95%CI - 81-100%), 63% (95%CI: 39-82%) and 62% (95%CI: 39-81%), respectively. 18F-FET PET/CT was true positive in 4 and true negative in 4 patients. Sensitivity, specificity and accuracy for 18F-FET PET/CT in HGG were 100%. Conclusion: 18F-DOPA and 18F-FET PET/CT have a similar diagnostic accuracy in patients with recurrent HGG. However, 18F-DOPA PET/CT could be affected by inflammation conditions (false positive) that can alter the final results. Large comparative trials are warranted in order to better understand the utility of 18F-DOPA or 18F-FET PET/CT in patients with HGG.

scholarly journals SpheroidPicker for automated 3D cell culture manipulation using deep learning

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Istvan Grexa ◽  
Akos Diosdi ◽  
Maria Harmati ◽  
Andras Kriston ◽  
Nikita Moshkov ◽  
...  
Keyword(s):  
Cell Culture ◽  
Precision Medicine ◽  
High Throughput Screening ◽  
Standard Sample ◽  
Ex Vivo ◽  
Low Cost ◽  
3D Cell Culture ◽  
Syringe Pump ◽  
Experimental Conditions ◽  
The Past

AbstractRecent statistics report that more than 3.7 million new cases of cancer occur in Europe yearly, and the disease accounts for approximately 20% of all deaths. High-throughput screening of cancer cell cultures has dominated the search for novel, effective anticancer therapies in the past decades. Recently, functional assays with patient-derived ex vivo 3D cell culture have gained importance for drug discovery and precision medicine. We recently evaluated the major advancements and needs for the 3D cell culture screening, and concluded that strictly standardized and robust sample preparation is the most desired development. Here we propose an artificial intelligence-guided low-cost 3D cell culture delivery system. It consists of a light microscope, a micromanipulator, a syringe pump, and a controller computer. The system performs morphology-based feature analysis on spheroids and can select uniform sized or shaped spheroids to transfer them between various sample holders. It can select the samples from standard sample holders, including Petri dishes and microwell plates, and then transfer them to a variety of holders up to 384 well plates. The device performs reliable semi- and fully automated spheroid transfer. This results in highly controlled experimental conditions and eliminates non-trivial side effects of sample variability that is a key aspect towards next-generation precision medicine.

Reoperation for Recurrent High-Grade Glioma

Neurosurgery ◽  
2014 ◽  
Vol 75 (5) ◽  
pp. 491-499 ◽  
Author(s):  
Shawn L. Hervey-Jumper ◽  
Mitchel S. Berger
Keyword(s):  
Patient Selection ◽  
Survival Benefit ◽  
Performance Status ◽  
High Grade Glioma ◽  
World Health ◽  
Time Interval ◽  
Extensive Literature ◽  
High Grade ◽  
Glioma Recurrence

Abstract Optimal treatment for recurrent high-grade glioma continues to evolve. Currently, however, there is no consensus in the literature on the role of reoperation in the management of these patients. In this analysis, we reviewed the literature to examine the role of reoperation in patients with World Health Organization grade III or IV recurrent gliomas, focusing on how reoperation affects outcome, perioperative complications, and quality of life. An extensive literature review was performed through the use of the PubMed and Ovid Medline databases for January 1980 through August 2013. A total 31 studies were included in the final analysis. Of the 31 studies with significant data from single or multiple institutions, 29 demonstrated a survival benefit or improved functional status after reoperation for recurrent high-grade glioma. Indications for reoperation included new focal neurological deficits, tumor mass effect, signs of elevated intracranial pressure, headaches, increased seizure frequency, and radiographic evidence of tumor progression. Age was not a contraindication to reoperation. Time interval of at least 6 months between operations and favorable performance status (Karnofsky Performance Status score ≥70) were important predictors of benefit from reoperation. Extent of resection at reoperation improved survival, even in patients with subtotal resection at initial operation. Careful patient selection such as avoiding those individuals with poor performance status and bevacizumab within 4 weeks of surgery is important. Although limited to retrospective analysis and patient selection bias, mounting evidence suggests a survival benefit in patients receiving a reoperation at the time of high-grade glioma recurrence.

Anlotinib alone or in combination with temozolomide in recurrent high-grade glioma: A retrospective study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14019-e14019
Author(s):  
Qun-ying Yang ◽  
Cheng-Cheng Guo ◽  
Zhenqiang He ◽  
Fuhua Lin ◽  
Ji Zhang ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Initial Dose ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Objective Response ◽  
High Grade Glioma ◽  
Combination Regimen ◽  
High Grade ◽  
Multikinase Inhibitor ◽  
Rano Criteria

e14019 Background: High-grade glioma (HGG) is the most common malignant brain tumor and lacks effective treatment regimen. Anlotinib is a multikinase inhibitor blocking angiogenesis and tumor cell proliferation simultaneously. This study was performed to evaluate the efficacy and safety of anlotinib alone or in combination with temozolomide (TMZ) in the treatment of recurrent HGG. Methods: This is a single-center, retrospective study. Eligible patients (pts) were diagnosed with pathologically confirmed high grades (WHO III/IV) glioma and had recurrent or progressive disease on or after prior treatment. Other key eligibility criteria included Karnofsky Performance Status (KPS) ≥ 40, aged 16 ̃75 years and having at least one measurable lesion (RANO criteria). Pts were administrated with anlotinib once daily for 14 days every 3 weeks till disease progression, intolerable toxicities or death. The initial dose was 12mg for younger pts ( < 40 years old) with KPS ≥ 60 and 10 mg for others. Combination treatment was allowed if previous TMZ was effective and tolerable. TMZ was administered on dose-dense schedule (150mg/m2, QD, d1-d7 and d15-d21 every 28 days) or metronomic schedule (25-50mg/m2 QD). The primary endpoint was progression-free survival at 6 months (PFS6m) accessed according to RANO criteria. The second endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR). Results: Between August 2019 and June 2020, 23 pts with HGG (15 grade IV; 8 grade III; 12 males, 11 females) were enrolled. The median age and median KPS was 42 years and 60. 16 pts have multifocal or disseminated disease. 18 pts received ≥2 lines previous treatment. At the data cutoff date on September 2020, the median duration of treatment was 9 weeks (range: 3-33). The PFS6m was 39.1% and the median PFS was 4.2 months (95% CI: 2.8, 5.6). The median OS was not reached (95% CI: NE, NE) and the OS at 12 months (OS12m) was 54.8%. 8 pts observed tumor response and 9 pts had stable disease. The ORR and DCR were 34.8% and 73.9% respectively. The results of survival analysis for subgroups were summarized in table below. Grade 1 or 2 treatment-related adverse events (TRAEs) occurred in 65.2% pts. No ≥ grade 3 TRAE was found. All hematological TRAEs occurred in patients received combination regimen. No TRAE-induced treatment termination occurred. The lower incidence of TRAE may partly attributed to that most pts (18/23) received lower initial dose (10mg) of anlotinib and the relatively shorter treatment duration. Conclusions: This study showed treatment with anlotinib alone or in combination with TMZ had promising efficacy and favorable tolerability in patients with recurrent HGG.[Table: see text]

A case series of salvage CCNU in high-grade glioma who have previously received temozolomide from a tertiary care institute in Mumbai

2016 ◽  
Vol 53 (4) ◽  
pp. 558 ◽  
Author(s):  
VM Patil ◽  
R Abhinav ◽  
R Tonse ◽  
S Epari ◽  
T Gupta ◽  
...  
Keyword(s):  
Tertiary Care ◽  
Case Series ◽  
High Grade Glioma ◽  
High Grade ◽  
Care Institute

KRN8602 (MX2-Hydrochloride): An Active New Agent for the Treatment of Recurrent High-Grade Glioma

1999 ◽  
Vol 17 (8) ◽  
pp. 2579-2579 ◽  
Author(s):  
Kerrie Clarke ◽  
Russell L. Basser ◽  
Craig Underhill ◽  
Peter Mitchell ◽  
Jane Bartlett ◽  
...  
Keyword(s):  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
High Grade Glioma ◽  
High Grade ◽  
Intravenous Bolus ◽  
Single Episode ◽  
Group Score ◽  
Nonhematologic Toxicity ◽  
Disease Stabilization ◽  
Grade 3

PURPOSE: To assess the efficacy and toxicity of KRN8602 when administered as an intravenous bolus to patients with recurrent high-grade malignant glioma. PATIENTS AND METHODS: Patients with recurrent or persistent anaplastic astrocytoma or glioblastoma multiforme who had not received recent chemotherapy or radiotherapy and were of good performance status (Eastern Cooperative Oncology Group score ≤ 2) were treated with an intravenous bolus of 40 mg/m2 KRN8602 every 28 days. Tumor responses were assessed radiologically and clinically after every second cycle of therapy. Treatment was continued until documented progression or a total of six cycles. RESULTS: A median of three cycles (range, one to six cycles) of KRN8602 was administered to 55 patients, 49 of whom received at least two cycles and were, therefore, assessable for response. The overall response rate (disease stabilization or better) was 43% (95% confidence interval, 29% to 58%). There were three complete responses, one partial response, seven minor responses, and 10 patients with stable disease. The median time to progression was 2 months (range, 1.5 to 37 months) and overall survival was 11 months (range, 1.5 to 40 months). Neutropenia was the most common toxicity, although it was generally of brief duration, and there were only seven episodes of febrile neutropenia in 176 cycles delivered. Nonhematologic toxicity was mostly gastrointestinal (nausea and vomiting, diarrhea) and events were grade 2 or lower except for a single episode of grade 3 vomiting. CONCLUSION: KRN8602 is an active new agent with minimal toxicity in the treatment of relapsed or refractory high-grade glioma. Further studies with KRN8602 in combination with other cytotoxics and in adjuvant treatment of gliomas are warranted.

Sign in / Sign up

Export Citation Format

Share Document