Phase 2 Study of Sorafenib, Valproic Acid, and Sildenafil in the Treatment of Recurrent High-Grade Glioma
Poklepovic, A.; Shah, P.; Tombes, M. B.; Shrader, E.; Bandyopadhyay, D.; Deng, X.; Roberts, C. H.; Ryan, A.; Hudson, D.; Sankala, H.; Kmieciak, M.; Dent, P.; Malkin, M.
Show abstract
Here we report the results of a single-center phase 2 clinical trial combining sorafenib tosylate, valproic acid, and sildenafil for the treatment of patients with recurrent high-grade glioma (NCT01817751). Clinical toxicities were grade 1 and grade 2, with one grade 3 toxicity for maculopapular rash (6.4%). For all evaluable patients, the median progression-free survival was 3.65 months and overall survival (OS) 10.0 months. There was promising evidence showing clinical activity and benefit. In the 33 evaluable patients, low protein levels of the chaperone GRP78 (HSPA5) was significantly associated with a better OS (p < 0.0026). A correlation between the expression of PDGFR and OS approached significance (p < 0.0728). Five patients presently have a mean OS of 73.6 months and remain alive. This is the first therapeutic intervention glioblastoma trial to significantly associate GRP78 expression to OS. Our data suggest that the combination of sorafenib tosylate, valproic acid, and sildenafil requires additional clinical development in the recurrent glioma population.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Effects of Combination Therapy of a CDK4/6 and MEK Inhibitor in Diffuse Midline Glioma Preclinical Models 94%
- Changes in the tumor microenvironment and treatment outcome in glioblastoma: A pilot study 94%
- The efficacy of a ketogenic diet in preclinical models of IDH wild-type and IDH mutant glioma 93%
Similar papers in this journal
- Clinical activity of MAPK targeted therapies in patients with non-V600 BRAF mutant tumors 95%
- Clinical activity of Mitogen-Activated Protein Kinase (MAPK) inhibitors in patients with MAP2K1 (MEK1)-mutated metastatic cancers 93%
- Cell-Free Tumor DNA Dominant Clone Allele Frequency (DCAF) Is Associated With Poor Outcomes In Advanced Biliary Cancers Treated With Platinum-Based Chemotherapy 93%
Similar papers in this journal
- DNA repair biomarkers to guide usage of combined PARP inhibitors and chemotherapy: a meta-analysis and systematic review 90%
- Arrest of mouse preterm labor until term delivery by combination therapy with atosiban and mundulone, a natural product with tocolytic efficacy 88%
- Cortistatin exerts an immunomodulatory and neuroprotective role in a preclinical model of ischemic stroke 88%
Similar papers in this journal
- Acquired and intrinsic resistance to vemurafenib in BRAFV600E-driven melanoma brain metastases 92%
- Phenotypic plasticity in a novel set of EGFR tyrosine kinase inhibitor-adapted non-small cell lung cancer cell lines 92%
- Signature reversion of three disease-associated gene signatures prioritizes cancer drug repurposing candidates 89%
Similar papers in this journal
- Novel kinome profiling technology reveals drug treatment is patient and 2D/3D model dependent in GBM 92%
- Meta-Analysis of Adenoviral p53 Gene Therapy Clinical Trials in Recurrent Head and Neck Squamous Cell Carcinoma 91%
- High Affinity Chimeric Antigen Receptor with Cross-Reactive scFv to Clinically Relevant EGFR Oncogenic Isoforms 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.