Development of sorafenib and other molecularly targeted agents in hepatocellular carcinoma

Zhu, Andrew X.

doi:10.1002/cncr.23175

Cited by 118 publications

(84 citation statements)

References 57 publications

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“…There is, therefore, a strong rationale for targeting growth factors that drive the angiogenic process as a potential therapeutic strategy for the treatment of HCC. VEGF is a key angiogenic factor, and several agents that target VEGF or VEGFR are currently in development for the treatment of HCC (Table 1) Bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA, USA) is a recombinant, humanized, anti-VEGF monoclonal antibody (Presta et al, 1997) that has shown encouraging early evidence of efficacy in patients with advanced HCC (Siegel et al, 2008;Zhu, 2008). In two small monotherapy studies, treatment with bevacizumab 5-10 mg/kg resulted in partial response (PR) in 8-13% of patients and stable disease (SD) in 54-72% of patients (Malka et al, 2007;Siegel et al, 2008).…”

Section: Therapeutic Targets In Hccmentioning

confidence: 99%

The role of signaling pathways in the development and treatment of hepatocellular carcinoma

2010

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Section: Therapeutic Targets In Hccmentioning

confidence: 99%

The role of signaling pathways in the development and treatment of hepatocellular carcinoma

2010

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“…Hepatocellular carcinoma is so infrequent in children that these patients have often been treated according to hepatoblastoma regimens, albeit with far less success. Recently, sorafenib, a multikinase inhibitor, was approved by the U.S. Food and Drug Administration for the first-line treatment of hepatocellular carcinoma after a study in adults demonstrated efficacy in advanced-stage hepatocellular carcinoma [44], but no data exist on its use in children. The approach to treatment of less common malignant tumors of the liver parallels the approach to the tumors with similar histology, that is, a primary hepatic sarcoma is generally treated like sarcomas in other anatomical sites.…”

Section: Treatmentmentioning

confidence: 99%

Liver Tumors in Children

2008

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After completing this course, the reader should be able to:1. Describe the current epidemiologic trends in hepatoblastoma.2. Identify the genetic syndromes that are seen in a subset of liver tumors.3. Assess the need for complete tumor resection in the treatment of liver tumors in children as well as the increasingly important option of liver transplantation for those patients with unresectable tumors.4. Discuss the impact of the hepatitis vaccine in reducing the incidence of hepatocellular carcinoma.5. Explain the prognostic impact of different histologic subtypes of hepatoblastoma.6. Promote the need for future clinical trials in testing new agents for hepatocellular carcinoma in children.7. Employ the different staging systems used in liver tumors, including the traditional North American postsurgical staging system and the European presurgical staging system using imaging.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACT

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“…9,10 These include derangements in the regulation of signal transduction pathways involved cell proliferation (Ras/Raf/MEK/ERK pathway) apoptosis and protein synthesis (PI3/AKT/mTOR pathway). 11 Angiogenesis also plays an important role in tumorigenesis because HCC is highly vascular.…”

Section: Commentmentioning

confidence: 99%

Sorafenib

Scanga

Kowdley

2009

Hepatology

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Background: No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma. Methods: In this multicenter, phase 3, double-blind, placebo-controlled trial, we randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or placebo. Primary outcomes were overall survival and the time to symptomatic progression. Secondary outcomes included the time to radiologic progression and safety. Results: At the second planned interim analysis, 321 deaths had occurred, and the study was stopped. Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (hazard ratio in the sorafenib group, 0.69; 95% confidence interval, 0.55 to 0.87; P < 0.001). There was no significant difference between the two groups in the median time to symptomatic progression (4.1 months vs. 4.9 months, respectively, P‫.)77.0؍‬ The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group (P < 0.001). Seven patients in the sorafenib group (2%) and two patients in the placebo group (1%) had a partial response; no patients had a com-

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Development of sorafenib and other molecularly targeted agents in hepatocellular carcinoma

Abstract: It is well appreciated that hepatocellular carcinoma (HCC) represents one of the most challenging malignancies of worldwide importance. In fact, HCC is the fifth most common cancer and the third most common cause of cancer-related death

Cited by 118 publications

References 57 publications

The role of signaling pathways in the development and treatment of hepatocellular carcinoma

The role of signaling pathways in the development and treatment of hepatocellular carcinoma

Liver Tumors in Children

Sorafenib

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