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Sorafenib for the treatment of unresectable hepatocellular carcinoma.

Furuse J - Biologics (2008)

Bottom Line: Sorafenib is an oral multi-kinase inhibitor that mainly targets Raf kinases and receptor tyrosine kinases associated with angiogenesis (VEGFR-2/-3, PDGFR-beta).Based on the results of the RCTs, sorafenib has been established as a standard agent for systemic chemotherapy in HCC patients with metastatic disease or transcatheter arterial chemoembolization (TACE)-refractory disease who are not suitable candidates for local treatments.The efficacy and safety of sorafenib in patients with moderate liver dysfunction have not been confirmed to date and more data are needed.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Medical Oncology, School of Medicine, Kyorin University.

ABSTRACT
Raf kinases and vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) tyrosine kinases are potential molecular targets for obtaining both anti-tumor cell progression and anti-angiogenesis effects in cancers, including hepatocellular carcinoma (HCC). Sorafenib is an oral multi-kinase inhibitor that mainly targets Raf kinases and receptor tyrosine kinases associated with angiogenesis (VEGFR-2/-3, PDGFR-beta). A global randomized controlled trial (RCT) of sorafenib versus placebo conducted in patients with advanced HCC demonstrated the beneficial effects of the drug on the time-to-progression and overall survival. Furthermore, a RCT with a similar design to that of the global trial conducted in the Asia-Pacific region also demonstrated the efficacy of the drug. The most common treatment-related adverse events of sorafenib were found to be diarrhea, fatigue, and skin toxicity, namely, hand-foot syndromes and rash. Based on the results of the RCTs, sorafenib has been established as a standard agent for systemic chemotherapy in HCC patients with metastatic disease or transcatheter arterial chemoembolization (TACE)-refractory disease who are not suitable candidates for local treatments. The efficacy and safety of sorafenib in patients with moderate liver dysfunction have not been confirmed to date and more data are needed. Development of new therapeutic methods is needed for the treatment of advanced HCC in the future; clinical trials of sorafenib-based combination therapy, second-line therapy after sorafenib failure, and adjuvant therapy after local treatments are warranted in HCC patients.

No MeSH data available.


Related in: MedlinePlus

Survival benefit was confirmed in the SHARP trial; the median overall survival was 10.7 months in the sorafenib group as compared with 7.9 months in the placebo group (hazard ratio for death in the sorafenib group, 0.69; 95% CI: 0.55–0.87). Reproduced with permission from Llovet JM, Ricci S, Mazzaferro V, et al 2008. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med, 359:378–90. Copyright © Massachusetts Medical Society. All rights reserved.
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f3-btt-2-779: Survival benefit was confirmed in the SHARP trial; the median overall survival was 10.7 months in the sorafenib group as compared with 7.9 months in the placebo group (hazard ratio for death in the sorafenib group, 0.69; 95% CI: 0.55–0.87). Reproduced with permission from Llovet JM, Ricci S, Mazzaferro V, et al 2008. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med, 359:378–90. Copyright © Massachusetts Medical Society. All rights reserved.


Sorafenib for the treatment of unresectable hepatocellular carcinoma.

Furuse J - Biologics (2008)

Survival benefit was confirmed in the SHARP trial; the median overall survival was 10.7 months in the sorafenib group as compared with 7.9 months in the placebo group (hazard ratio for death in the sorafenib group, 0.69; 95% CI: 0.55–0.87). Reproduced with permission from Llovet JM, Ricci S, Mazzaferro V, et al 2008. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med, 359:378–90. Copyright © Massachusetts Medical Society. All rights reserved.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2727884&req=5

f3-btt-2-779: Survival benefit was confirmed in the SHARP trial; the median overall survival was 10.7 months in the sorafenib group as compared with 7.9 months in the placebo group (hazard ratio for death in the sorafenib group, 0.69; 95% CI: 0.55–0.87). Reproduced with permission from Llovet JM, Ricci S, Mazzaferro V, et al 2008. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med, 359:378–90. Copyright © Massachusetts Medical Society. All rights reserved.
Bottom Line: Sorafenib is an oral multi-kinase inhibitor that mainly targets Raf kinases and receptor tyrosine kinases associated with angiogenesis (VEGFR-2/-3, PDGFR-beta).Based on the results of the RCTs, sorafenib has been established as a standard agent for systemic chemotherapy in HCC patients with metastatic disease or transcatheter arterial chemoembolization (TACE)-refractory disease who are not suitable candidates for local treatments.The efficacy and safety of sorafenib in patients with moderate liver dysfunction have not been confirmed to date and more data are needed.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Medical Oncology, School of Medicine, Kyorin University.

ABSTRACT
Raf kinases and vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) tyrosine kinases are potential molecular targets for obtaining both anti-tumor cell progression and anti-angiogenesis effects in cancers, including hepatocellular carcinoma (HCC). Sorafenib is an oral multi-kinase inhibitor that mainly targets Raf kinases and receptor tyrosine kinases associated with angiogenesis (VEGFR-2/-3, PDGFR-beta). A global randomized controlled trial (RCT) of sorafenib versus placebo conducted in patients with advanced HCC demonstrated the beneficial effects of the drug on the time-to-progression and overall survival. Furthermore, a RCT with a similar design to that of the global trial conducted in the Asia-Pacific region also demonstrated the efficacy of the drug. The most common treatment-related adverse events of sorafenib were found to be diarrhea, fatigue, and skin toxicity, namely, hand-foot syndromes and rash. Based on the results of the RCTs, sorafenib has been established as a standard agent for systemic chemotherapy in HCC patients with metastatic disease or transcatheter arterial chemoembolization (TACE)-refractory disease who are not suitable candidates for local treatments. The efficacy and safety of sorafenib in patients with moderate liver dysfunction have not been confirmed to date and more data are needed. Development of new therapeutic methods is needed for the treatment of advanced HCC in the future; clinical trials of sorafenib-based combination therapy, second-line therapy after sorafenib failure, and adjuvant therapy after local treatments are warranted in HCC patients.

No MeSH data available.


Related in: MedlinePlus