A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_session9ndrpe94ehd3sp8ic3gjsg6dvoqe25mq): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "choices"

Filename: controllers/Detail.php

Line Number: 249

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 249

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 249

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 249

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: 8192

Message: strpos(): Passing null to parameter #1 ($haystack) of type string is deprecated

Filename: models/Detail_model.php

Line Number: 71

Backtrace:

File: /var/www/html/application/models/Detail_model.php
Line: 71
Function: strpos

File: /var/www/html/application/controllers/Detail.php
Line: 252
Function: insertAPISummary

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: 8192

Message: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated

Filename: helpers/my_audit_helper.php

Line Number: 8919

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 8919
Function: str_replace

File: /var/www/html/application/controllers/Detail.php
Line: 255
Function: formatAIDetailSummary

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "choices"

Filename: controllers/Detail.php

Line Number: 256

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 256

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 256

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "usage"

Filename: controllers/Detail.php

Line Number: 257

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 257

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "usage"

Filename: controllers/Detail.php

Line Number: 258

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 258

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "usage"

Filename: controllers/Detail.php

Line Number: 259

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 259
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 259

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 259
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "usage"

Filename: controllers/Detail.php

Line Number: 260

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 260

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 260

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

Multicenter Phase IB Trial of Carboxyamidotriazole Orotate and Temozolomide for Recurrent and Newly Diagnosed Glioblastoma and Other Anaplastic Gliomas. | LitMetric

Multicenter Phase IB Trial of Carboxyamidotriazole Orotate and Temozolomide for Recurrent and Newly Diagnosed Glioblastoma and Other Anaplastic Gliomas.

J Clin Oncol

Antonio Omuro, University of Miami, Miami, FL; Kathryn Beal, Robert J. Young, Thomas J. Kaley, Lisa M. DeAngelis, Mariza Daras, Igor T. Gavrilovic, Ingo Mellinghoff, Eli L. Diamond, Andrew McKeown, Malbora Manne, Andrew Caterfino, Krishna Patel, Philip Gutin, Viviane Tabar, Debyani Chakravarty, Timothy A. Chan, Cameron W. Brennan, and Elena Pentsova, Memorial Sloan Kettering Cancer Center; Rashida A. Karmali, Tactical Therapeutics, Inc, New York; Katharine McNeill, Montefiore Medical Center, Bronx, NY; Alissa Thomas, University of Vermont, Burlington, VT; Xuling Lin, National Neuroscience Institute, Singapore; Robert Terziev, University Hospital, Zurich, Switzerland; Linda Bavisotto, Porta Clinica PLLC, Seattle, WA; Greg Gorman, Samford University McWhorter School of Pharmacy, Birmingham, AL; Michael Lamson, Nuventra Pharma Sciences, Durham, NC; and Elizabeth Garrett-Mayer, Medical University of South Carolina, Charleston, SC.

Published: June 2018

AI Article Synopsis

Article Abstract

Purpose Carboxyamidotriazole orotate (CTO) is a novel oral inhibitor of non-voltage-dependent calcium channels with modulatory effects in multiple cell-signaling pathways and synergistic effects with temozolomide (TMZ) in glioblastoma (GBM) models. We conducted a phase IB study combining CTO with two standard TMZ schedules in GBM. Methods In cohort 1, patients with recurrent anaplastic gliomas or GBM received escalating doses of CTO (219 to 812.5 mg/m once daily or 600 mg fixed once-daily dose) combined with TMZ (150 mg/m 5 days during each 28-day cycle). In cohort 2, patients with newly diagnosed GBM received escalating doses of CTO (219 to 481 mg/m/d once daily) with radiotherapy and TMZ 75 mg/m/d, followed by TMZ 150 mg to 200 mg/m 5 days during each 28-day cycle. Results Forty-seven patients were enrolled. Treatment was well tolerated; toxicities included fatigue, constipation, nausea, and hypophosphatemia. Pharmacokinetics showed that CTO did not alter TMZ levels; therapeutic concentrations were achieved in tumor and brain. No dose-limiting toxicities were observed; the recommended phase II dose was 600 mg/d flat dose. Signals of activity in cohort 1 (n = 27) included partial (n = 6) and complete (n = 1) response, including in O-methylguanine-DNA methyltransferase unmethylated and bevacizumab-refractory tumors. In cohort 2 (n = 15), median progression-free survival was 15 months and median overall survival was not reached (median follow-up, 28 months; 2-year overall survival, 62%). Gene sequencing disclosed a high rate of responses among EGFR-amplified tumors ( P = .005), with mechanisms of acquired resistance possibly involving mutations in mismatch-repair genes and/or downstream components TSC2, NF1, NF2, PTEN, and PIK3CA. Conclusion CTO can be combined safely with TMZ or chemoradiation in GBM and anaplastic gliomas, displaying favorable brain penetration and promising signals of activity in this difficult-to-treat population.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993168PMC
http://dx.doi.org/10.1200/JCO.2017.76.9992DOI Listing

Publication Analysis

Top Keywords

anaplastic gliomas
12
carboxyamidotriazole orotate
8
newly diagnosed
8
cohort patients
8
gbm received
8
received escalating
8
escalating doses
8
doses cto
8
cto 219
8
tmz 150
8

Similar Publications

Background: This study is a phase II clinical trial to evaluate the efficacy, safety, and tolerability of the blood-brain barrier (BBB) permeable peptide-paclitaxel conjugate ANG1005 in patients with recurrent high-grade glioma (HGG) (NCT01967810).

Methods: Seventy-three patients were enrolled in 3 separate arms-recurrent glioblastoma (GBM) (Arm 1), bevacizumab refractory GBM (Arm 2), and grade 3 anaplastic gliomas (AGs) (Arm 3). The study was started in October 2013, and the data were locked on September 29, 2017.

View Article and Find Full Text PDF

Background: Combination therapy with BRAF and MEK inhibitor holds promise for treating gliomas harboring the V600E mutation; however, the development of acquired resistance remains a challenge.

Case Description: We describe a case of repeated recurrent mutant pleomorphic xanthoastrocytoma (central nervous system World Health Organization grade 3) treated with combination therapy with BRAF and MEK inhibitor. The patient received dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor); however, she developed resistance to the combination therapy.

View Article and Find Full Text PDF
Article Synopsis
  • This study investigates the relationship between motor deficits (MD) in patients after glioma surgery and the proximity of the tumor to key motor pathways, specifically the corticospinal tract (CST).
  • It compares two imaging techniques—conventional Diffusion Tensor Imaging Fiber Tracking (DTI-FT) and q-ball Imaging Fiber Tracking (QBI-FT)—to determine which better predicts postoperative motor impairment.
  • Preliminary results indicate that patients with more severe MD have lesions significantly closer to the CST when analyzed using QBI-FT, suggesting this method could improve neurosurgical planning, although more extensive research is needed to validate these findings.
View Article and Find Full Text PDF

Purpose: Lower-grade gliomas typically exhibit 5-aminolevulinic acid (5-ALA)-induced fluorescence in only 20-30% of cases, a rate that can be increased by doubling the administered dose of 5-ALA. Fluorescence can depict anaplastic foci, which can be precisely sampled to avoid undergrading. We aimed to analyze whether a deep learning model could predict intraoperative fluorescence based on preoperative magnetic resonance imaging (MRI).

View Article and Find Full Text PDF

Stereotactic Photodynamic Therapy of Recurrent Malignant Gliomas.

Sovrem Tekhnologii Med

November 2024

MD, PhD, Associate Professor, Head of the Department of Neurosurgery; Military Medical Academy named after S.M. Kirov, 6 Academician Lebedev St., Saint Petersburg, 194044, Russia.

Unlabelled: is to assess the effectiveness and safety of stereotactic photodynamic therapy (sPDT) with 5-aminolevulinic acid (5-ALA) in patients with recurrent malignant supratentorial gliomas in functionally relevant brain areas.

Materials And Methods: In a retrospective single-center study the results of sPDT with 5-ALA in 10 patients (6 of 10 were male), aged 30 to 62 years (median: 51.5 years; 95% CI: 38-59 years) with recurrent malignant brain gliomas after standard therapy who underwent surgery during the period of 2020-2023 were analyzed.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!