Selection of Patients with Hepatocellular Carcinoma for Sorafenib

2009 ◽  
Vol 7 (4) ◽  
pp. 397-403 ◽  
Author(s):  
Ghassan K. Abou-Alfa
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinase Inhibitor ◽  
Locally Advanced ◽  
Phase Iii ◽  
Vegf Receptor ◽  
Raf Kinase ◽  
Advanced Cirrhosis ◽  
Phase Iii Studies ◽  
Selection Of Patients ◽  
Selection Of

Sorafenib, a multitargeted anti-VEGF receptor and raf kinase inhibitor, was recently approved by the FDA for treating unresectable hepatocellular carcinoma (HCC) based on 2 randomized phase III studies. In addition, a phase II study evaluating sorafenib in patients with HCC and Child-Pugh A and B and a phase I study evaluating sorafenib in patients with organ dysfunction have provided insight about the safety and efficacy of sorafenib in patients with HCC and more advanced cirrhosis, and any difference in outcome based on etiology of HCC. The lack of objective responses observed in the sorafenib arm in the SHARP study also raises practical issues about how to assess response or efficacy of the therapy and thus how long a patient should receive sorafenib. This article addresses these questions on the use of sorafenib in HCC, both in the locally advanced and metastatic settings, in addition to the potential future applications and uses of sorafenib.

scholarly journals Scientific Rationale for Combined Immunotherapy with PD-1/PD-L1 Antibodies and VEGF Inhibitors in Advanced Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1089 ◽  
Author(s):  
Masatoshi Kudo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Vegf Receptor ◽  
Advanced Hepatocellular Carcinoma ◽  
Vegf Inhibitors ◽  
Phase Iii Trial ◽  
Phase Iii Clinical Trials ◽  
Immunosuppressive Microenvironment

A successful phase III trial for the combination of atezolizumab and bevacizumab (the IMbrave150 trial) in advanced hepatocellular carcinoma has recently been reported. This is groundbreaking because nivolumab and pembrolizumab, both programmed cell death-1 (PD-1) antibodies, have failed to show efficacy as first- and second-line therapeutics, respectively, in phase III clinical trials. Immunotherapy with a combination of atezolizumab and bevacizumab resulted in better survival than treatment with sorafenib for the first time since sorafenib was approved in 2007. The high efficacy of the combination of PD-1/programmed death ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF) antibodies is not only due to their additive effects on tumor growth, but also to their reprogramming of the immunosuppressive microenvironment into an immunostimulatory microenvironment. These results were confirmed in a phase Ib trial that showed significantly longer progression-free survival in the atezolizumab plus bevacizumab group than in patients that received atezolizumab alone. These results demonstrate that immunotherapy with a combination of PD-1/PD-L1 and VEGF inhibitors is effective and may result in a reprogramming of the tumor microenvironment. The results of an ongoing phase III trial of a PD-1 antibody in combination with the VEGF receptor tyrosine kinase inhibitor (TKI) are highly anticipated.

scholarly journals PHARMACOLOGICAL THERAPY OF HEPATOCELLULAR CANCER PRACTICAL ISSUES AND SOLUTIONS

2017 ◽  
pp. 11-23
Author(s):  
V. V. Breder ◽  
K. K. Laktionov ◽  
M. I. Davydov
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinase Inhibitor ◽  
Locally Advanced ◽  
Hepatocellular Cancer ◽  
Pharmacological Therapy ◽  
Second Line Therapy ◽  
Clinical Issue ◽  
Pharmaceutical Therapy ◽  
Hepatocellular Carcinomas ◽  
Strategic Goal

Pharmaceutical therapy of hepatocellular carcinoma represents a major clinical issue of debate in modern oncology. Until now, Sorafenib remains the only option for the management of locally advanced and metastatic hepatocellular carcinomas, which increases the overall survival of patients. In the absence of alternative treatment, the oncologist understanding of the place, time, the strategic goal and tactical objectives of the pharmaceutical therapy of hepatocellular carcinoma at different stages of cancer is of great importance. The article considers the practical aspects of the Sorafenib therapy of hepatocellular cancer in various clinical situations, and proposes algorithms of accompanying therapy for the underlying liver pathology. It presents the results of Regorafenib therapy, a new multi-kinase inhibitor, which significantly increases survival in the second line therapy of sorafenib-resistant hepatocellular  carcinoma. The options  of  pharmaceutical therapy for hepatocellular  carcinoma using cytotoxic and molecular-directed medicines, prospects of modern immunotherapy are discussed.

Platinum ineligibility in squamous cell carcinoma of the head and neck: consensus from Central America and the Caribbean

2021 ◽  
Author(s):  
Juan F Alvarado-Muñoz ◽  
Agustín Falco ◽  
Agatha R Morales ◽  
Noé C Sánchez ◽  
Giovanni Reynoso ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Central America ◽  
Squamous Cell ◽  
Locally Advanced ◽  
High Incidence ◽  
The Caribbean ◽  
Selection Of Patients ◽  
Selection Of

The high incidence of head and neck cancer in Central America and the Caribbean, together with limitations in the healthcare system for patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) in this region necessitate a consensus of opinion based on a review of the literature on therapy with cisplatin plus radiation. Such an approach will ensure appropriate selection of patients who can benefit from therapy and reduce the incidence of related adverse events. Therefore, we recorded the opinion of experts in the region in order to identify needs and challenges in the treatment of LA SCCHN.

scholarly journals Cabozantinib in combination with atezolizumab versus sorafenib in treatment-naive advanced hepatocellular carcinoma: COSMIC-312 Phase III study design

2020 ◽  
Vol 16 (21) ◽  
pp. 1525-1536 ◽  
Author(s):  
Robin Kate Kelley ◽  
Jennifer W Oliver ◽  
Saswati Hazra ◽  
Fawzi Benzaghou ◽  
Thomas Yau ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinase Inhibitor ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Single Agent Therapy ◽  
Treatment Naïve ◽  
Phase Iii Study ◽  
Immunomodulatory Properties

Cabozantinib is an oral tyrosine kinase inhibitor that targets VEGFR, MET and the TAM (TYRO3, AXL, MER) family of kinase receptors. In addition to their role in tumor growth and angiogenesis, cabozantinib targets promote an immune-suppressive microenvironment. Cabozantinib is approved as single-agent therapy for patients with advanced hepatocellular carcinoma who received prior sorafenib. Owing to its antitumor and immunomodulatory properties, cabozantinib is being developed in combination with immune checkpoint inhibitors. Early studies of these combinations have shown promising antitumor activity and tolerability in patients with solid tumors. Here, we describe the rationale and design of COSMIC-312, a Phase III study evaluating the safety and efficacy of cabozantinib in combination with atezolizumab (anti–PD-L1 monoclonal antibody) versus sorafenib for treatment-naive patients with advanced hepatocellular carcinoma. ClinicalTrial.gov Registration: NCT03755791

scholarly journals Population Exposure-Response Modeling Supported Selection of Naloxegol Doses in Phase III Studies in Patients With Opioid-Induced Constipation

2017 ◽  
Vol 6 (10) ◽  
pp. 705-711 ◽  
Author(s):  
Nidal Al-Huniti ◽  
Hongmei Xu ◽  
Diansong Zhou ◽  
Sergey Aksenov ◽  
Robert Fox ◽  
...  
Keyword(s):  
Phase Iii ◽  
Population Exposure ◽  
Exposure Response ◽  
Response Modeling ◽  
Phase Iii Studies ◽  
Selection Of

scholarly journals Thymostimulin versus placebo for palliative treatment of locally advanced or metastasised hepatocellular carcinoma: a phase III clinical trial

BMC Cancer ◽  
2010 ◽  
Vol 10 (1) ◽  
Author(s):  
Matthias M Dollinger ◽  
◽  
Christine Lautenschlaeger ◽  
Joachim Lesske ◽  
Andrea Tannapfel ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trial ◽  
Palliative Treatment ◽  
Locally Advanced ◽  
Phase Iii ◽  
Phase Iii Clinical Trial
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