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Regorafenib: an evidence-based review of its potential in patients with advanced liver cancer.

Ravi S, Singal AK - Core Evid (2014)

Bottom Line: In spite of HCC surveillance with repeated imaging, about 50% of patients are diagnosed at an advanced stage and are not amenable to curative treatment options.Sorafenib, a multikinase inhibitor, remains the standard of care for advanced HCC.Regorafenib, another multikinase inhibitor, has demonstrated inhibition of a broader range of kinases, along with higher inhibition potential in preclinical models.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

ABSTRACT
Hepatocellular carcinoma (HCC) is the second-most common cause of cancer-related death in the world. In spite of HCC surveillance with repeated imaging, about 50% of patients are diagnosed at an advanced stage and are not amenable to curative treatment options. Sorafenib, a multikinase inhibitor, remains the standard of care for advanced HCC. Over the last 5 years, several other medications have been tested in Phase III trials. However, they have not shown any added benefit over sorafenib. Regorafenib, another multikinase inhibitor, has demonstrated inhibition of a broader range of kinases, along with higher inhibition potential in preclinical models. After its safety and pharmacological properties was studied in Phase I trials, a Phase II study evaluating the role of Regorafenib in patients with advanced HCC who progressed on sorafenib therapy demonstrated efficacy and a manageable safety profile. A Phase III trial is ongoing, and its result will help us better evaluate the role of Regorafenib in patients with advanced HCC.

No MeSH data available.


Related in: MedlinePlus

Structure of Regorafenib. 4-(4-[{(4-Chloro-3-[trifluoromethyl]phenyl) carbamoyl}amino]-3-fluorophenoxy)-N-methylpyridine-2-carboxamide.
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f3-ce-9-081: Structure of Regorafenib. 4-(4-[{(4-Chloro-3-[trifluoromethyl]phenyl) carbamoyl}amino]-3-fluorophenoxy)-N-methylpyridine-2-carboxamide.

Mentions: Regorafenib is a novel multikinase inhibitor belonging to the group of biaryl urea chemicals. Its chemical name is 4-(4-[{(4-chloro-3-[trifluoromethyl]phenyl)carbamoyl} amino]-3-fluorophenoxy)-N-methylpyridine-2-carboxamide hydrate. The structure of Regorafenib (Figure 3) is very similar to sorafenib, except for a fluorine atom in the center phenyl ring.27,28 This structural change results in a broader spectrum of kinase inhibition and a higher inhibition potential (Table 1).29,30 Studies using Regorafenib have shown potent inhibition of angiogenic and stromal receptor tyrosine kinases, including VEGFR-1, VEGFR-2, VEGFR-3, PDGFRβ, FGFR-1, and tyrosine kinase with immunoglobulin and epidermal growth-factor homology domain 2. It has also shown activity against oncogenic receptor tyrosine kinases and intracellular signaling kinases.31


Regorafenib: an evidence-based review of its potential in patients with advanced liver cancer.

Ravi S, Singal AK - Core Evid (2014)

Structure of Regorafenib. 4-(4-[{(4-Chloro-3-[trifluoromethyl]phenyl) carbamoyl}amino]-3-fluorophenoxy)-N-methylpyridine-2-carboxamide.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109634&req=5

f3-ce-9-081: Structure of Regorafenib. 4-(4-[{(4-Chloro-3-[trifluoromethyl]phenyl) carbamoyl}amino]-3-fluorophenoxy)-N-methylpyridine-2-carboxamide.
Mentions: Regorafenib is a novel multikinase inhibitor belonging to the group of biaryl urea chemicals. Its chemical name is 4-(4-[{(4-chloro-3-[trifluoromethyl]phenyl)carbamoyl} amino]-3-fluorophenoxy)-N-methylpyridine-2-carboxamide hydrate. The structure of Regorafenib (Figure 3) is very similar to sorafenib, except for a fluorine atom in the center phenyl ring.27,28 This structural change results in a broader spectrum of kinase inhibition and a higher inhibition potential (Table 1).29,30 Studies using Regorafenib have shown potent inhibition of angiogenic and stromal receptor tyrosine kinases, including VEGFR-1, VEGFR-2, VEGFR-3, PDGFRβ, FGFR-1, and tyrosine kinase with immunoglobulin and epidermal growth-factor homology domain 2. It has also shown activity against oncogenic receptor tyrosine kinases and intracellular signaling kinases.31

Bottom Line: In spite of HCC surveillance with repeated imaging, about 50% of patients are diagnosed at an advanced stage and are not amenable to curative treatment options.Sorafenib, a multikinase inhibitor, remains the standard of care for advanced HCC.Regorafenib, another multikinase inhibitor, has demonstrated inhibition of a broader range of kinases, along with higher inhibition potential in preclinical models.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

ABSTRACT
Hepatocellular carcinoma (HCC) is the second-most common cause of cancer-related death in the world. In spite of HCC surveillance with repeated imaging, about 50% of patients are diagnosed at an advanced stage and are not amenable to curative treatment options. Sorafenib, a multikinase inhibitor, remains the standard of care for advanced HCC. Over the last 5 years, several other medications have been tested in Phase III trials. However, they have not shown any added benefit over sorafenib. Regorafenib, another multikinase inhibitor, has demonstrated inhibition of a broader range of kinases, along with higher inhibition potential in preclinical models. After its safety and pharmacological properties was studied in Phase I trials, a Phase II study evaluating the role of Regorafenib in patients with advanced HCC who progressed on sorafenib therapy demonstrated efficacy and a manageable safety profile. A Phase III trial is ongoing, and its result will help us better evaluate the role of Regorafenib in patients with advanced HCC.

No MeSH data available.


Related in: MedlinePlus