A randomized phase II/III trial of a tumor vascular disrupting agent fosbretabulin tromethamine (CA4P) with carboplatin (C) and paclitaxel (P) in anaplastic thyroid cancer (ATC): Final survival analysis for the FACT trial.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 5502-5502 ◽  
Author(s):  
J. A. Sosa ◽  
R. Elisei ◽  
B. Jarzab ◽  
C. S. Bal ◽  
H. Koussis ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Thyroid Cancer ◽  
Phase Ii ◽  
Anaplastic Thyroid Cancer ◽  
Vascular Disrupting Agent ◽  
Randomized Phase Ii ◽  
Final Survival ◽  
Vascular Disrupting

Identification of potential key genes in anaplastic thyroid cancer using bioinformatics analysis

2021 ◽  
Author(s):  
Zhenzhen Li ◽  
Xiong Chaoliang ◽  
Jin Wei ◽  
Ping Chen ◽  
Yanping Zhang ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Thyroid Cancer ◽  
Target Genes ◽  
Collagen Type ◽  
Expression Profiles ◽  
Thyroid Tissue ◽  
Anaplastic Thyroid Cancer ◽  
Type I ◽  
Tissue Samples ◽  
Km Plotter

Abstract Background Anaplastic thyroid cancer (ATC) has a high degree of malignancy and a poor prognosis. Its incidence accounts for approximately 10–15% of all thyroid cancers. The purpose of this study was to determine the differentially expressed genes (DEGs) of ATC through biometric analysis technology, clarify the potential interactions between them, and screen genes related to the prognosis of ATC. Methods The GSE29265, GSE65144, GSE33630, and GSE85457 expression profiles downloaded from the Gene Expression Omnibus database (GEO) contained a total of 117 tissue samples (81 normal thyroid tissue samples and 36 ATC samples). The four datasets were integrated and analyzed by the limma packages to obtain DEGs. With these DEGs, we performed gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analyses using the Database for Annotation, Visualization and Integrated Discovery, protein-protein interaction (PPI) analysis using Cytoscape, and survival analysis using the Kaplan-Meier (KM) plotter. Results. After R integration analysis of the four datasets, 764 DEGs were obtained, i.e., 314 upregulated and 450 downregulated genes. Among the hub DEGs obtained in the PPI network, the expression levels of thymidylate synthase (TYMS), fibronectin 1, chordin-like 1, syndecan 2, integrin alpha 2, collagen type I alpha 1 chain, collagen type IX alpha 3 chain (COL9A3), and collagen type XXIII alpha 1 chain (COL23A1) were associated with ATC prognosis. These results showed that the overall survival and recurrence-free survival of TYMS, COL9A3, and COL23A1 were statistically significant in our KM plotter survival analysis; thus, these DEGs may be used as potential biomarkers of ATC. Conclusion This study identified several potential target genes and pathways that may affect the development of ATC. These findings provide new insights for the detection of novel diagnostic and therapeutic biomarkers for ATC.

scholarly journals A Phase II Study of Imatinib in Patients with Advanced Anaplastic Thyroid Cancer

Thyroid ◽  
2010 ◽  
Vol 20 (9) ◽  
pp. 975-980 ◽  
Author(s):  
Huan T. Ha ◽  
Julia S. Lee ◽  
Susan Urba ◽  
Ronald J. Koenig ◽  
James Sisson ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Anaplastic Thyroid Cancer

Witnessing a New Era? – The Emerging Role of Targeted Drugs in the Medical Treatment of Advanced Medullary and Anaplastic Thyroid Cancer

2010 ◽  
Vol 8 (2) ◽  
pp. 122
Author(s):  
Jochen Lorch ◽  
Wieland Voigt ◽  
◽  
Keyword(s):  
Thyroid Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Treatment Strategies ◽  
Anaplastic Thyroid Cancer ◽  
Phase Iii ◽  
Clinical Activity ◽  
Phase Ii Trials ◽  
New Era ◽  
Cancer Subtypes

The treatment of advanced thyroid cancer is currently entering a new era due to the introduction of targeted therapy into modern cancer treatment. The growing insight into the molecular biology of thyroid cancer and on the development of numerous mainly multitargeted agents provide the basis for new treatment strategies. In particular, activation of mitogenic and angiogenic signalling pathways are suitable targets as preclinical and clinical data suggest. Several Phase II and a few Phase III studies were launched in thyroid cancer which included medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC) but only a few focused specifically on theses subtypes. A number of smaller Phase II trials reported promising response rates and progression-free survival. Results from a randomised Phase III trial in MTC with vandetanib, a combined vascular endothelial growth factor receptor 2 + 3 (VEGF-R2+3) and RET multi tyrosine kinase inhibitor demonstrated significant clinical activity and resulted in the first approval of a kinase inhibitor for the treatment of MTC in 2011. Unlike in MTC, in ATC the prognosis is dismal due to the aggressive nature of the disease. Some mainly vascular targeting agents alone or in combination with chemotherapy have shown interesting activity in this disease and have raised new hope. Particularly the combination of fosbretabulin with a chemotherapy backbone of paclitaxel and carboplatin tripled the one-year survival rate in a recent Phase II trial which included 80 patients with ATC. In this review, we provide a brief overview of the general treatment concept of MTC and ATC and summarise the compiled evidence published on targeted agents in these rare thyroid cancer subtypes.

Witnessing a New Era?—The Emerging Role of Targeted Drugs in the Medical Treatment of Advanced Medullary and Anaplastic Thyroid Cancer

2012 ◽  
Vol 08 (02) ◽  
pp. 122
Author(s):  
Jochen Lorch ◽  
Wieland Voigt ◽  
◽  
Keyword(s):  
Thyroid Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Treatment Strategies ◽  
Anaplastic Thyroid Cancer ◽  
Phase Iii ◽  
Clinical Activity ◽  
Phase Ii Trials ◽  
New Era ◽  
Cancer Subtypes

The treatment of advanced thyroid cancer is currently entering a new era due to the introduction of targeted therapy into modern cancer treatment. The growing insight into the molecular biology of thyroid cancer and on the development of numerous mainly multitargeted agents provide the basis for new treatment strategies. In particular, activation of mitogenic and angiogenic signaling pathways are suitable targets as preclinical and clinical data suggest. Several Phase II and a few Phase III studies were launched in thyroid cancer which included medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC) but only a few focused specifically on theses subtypes. A number of smaller Phase II trials reported promising response rates and progression-free survival. Results from a randomized Phase III trial in MTC with vandetanib, a combined vascular endothelial growth factor receptor 2 + 3 (VEGF-R2+3) and RET multi tyrosine kinase inhibitor demonstrated significant clinical activity and resulted in the first approval of a kinase inhibitor for the treatment of MTC in 2011. Unlike in MTC, in ATC the prognosis is dismal due to the aggressive nature of the disease. Some mainly vascular targeting agents alone or in combination with chemotherapy have shown interesting activity in this disease and have raised new hope. Particularly the combination of fosbretabulin with a chemotherapy backbone of paclitaxel and carboplatin tripled the one-year survival rate in a recent Phase II trial which included 80 patients with ATC. In this review, we provide a brief overview of the general treatment concept of MTC and ATC and summarize the compiled evidence published on targeted agents in these rare thyroid cancer subtypes.

Association of baseline IL-8 and ferritin with clinical outcome with everolimus and BNC105P in the DisrupTOR-1 trial.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 475-475
Author(s):  
Sumanta Kumar Pal ◽  
Arun Azad ◽  
Sumeet Bhatia ◽  
Harry A. Drabkin ◽  
Brian Addis Costello ◽  
...  
Keyword(s):  
Phase Ii ◽  
Progression Free Survival ◽  
Sex Hormone Binding Globulin ◽  
Vascular Disrupting Agent ◽  
Kaplan Meier ◽  
Randomized Phase Ii ◽  
Lower Baseline ◽  
Before And After ◽  
Study Component ◽  
Metalloproteinase 9

475 Background: The vascular disrupting agent (VDA) BNC105P shows synergy with everolimus in preclinical models. The DisrupTOR-1 trial included a phase I component exploring this combination and a randomized phase II component comparing everolimus with BNC105P (Arm A) to everolimus monotherapy (Arm B) (Pal et al. ESMO 2014). Methods: Pts with clear cell mRCC and 1-2 prior therapies (including ≥1 VEGF-TKI) were randomized in the phase II study component. In Arm A, patients received a 7 day lead-in dose of everolimus followed by dosing with BNC105P. Patients in Arm A had optional blood collections prior to administration of BNC105P and 3 hours after receiving BNC105P. A fluorescence-based assay was used to characterize a broad panel of analytes at each time point. Biomarkers were assessed in both a static and dynamic fashion. For the former, biomarkers were stratified by median value, and progression-free survival (PFS) was compared in resulting subgroups using the Kaplan-Meier method. For the latter, change in biomarker level before and after BNC105P infusion was stratified by median difference, and PFS was compared in resulting subgroups using the Kaplan-Meier method. Results: 139 pts were randomized with 69 and 67 evaluable pts in Arms A and B, respectively. Dynamic biomarkers were assessed in a total of 44 patients who received everolimus with BNC105P. Increases in matrix metalloproteinase-9 (MMP-9) and stem cell factor (SCF) were associated with improved PFS (p=0.0421 and p=0.0291, respectively). Decreases in sex hormone binding globulin (SHBG) and serum amyloid protein (SAP) were associated with improved PFS (p=0.0184 and p=0.0063). With respect to static biomarkers, elevated baseline ferritin and lower baseline IL-8 were associated with improved PFS (p=0.0291 and p=0.0149, respectively). Conclusions: Several static and dynamic biomarkers in the DisrupTOR-1 trial were associated with PFS. A prospective biomarker-driven study examining everolimus with BNC105P selected by baseline IL-8 and ferritin is in development. Clinical trial information: NCT01034631.

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