Phase 1 Trial of Sorafenib and Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

Brade, Anthony; Ng, Sylvia S. W.; Brierley, James D.; Kim, John; Dinniwell, Robert; Ringash, Jolie; Wong, Rebecca; Cho, Charles; Knox, Jennifer J.; Dawson, Laura A.

doi:10.1016/j.ijrobp.2015.11.048

Cited by 96 publications

(82 citation statements)

References 17 publications

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“…Brade et al reported outcomes from a phase I trial of concurrent SBRT and sorafenib 45 . Overall there were 9, 2 and 1 episodes of grade 3, 4 (liver enzyme changes and small bowel obstruction) and 5 (upper GI bleed/ HCC rupture) toxicities, at least possibly attributable to SBRT.…”

Section: Sbrt and Sorafenibmentioning

confidence: 99%

Advances in Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

Murray

Dawson

2017

Seminars in Radiation Oncology

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SBRT is an emerging effective treatment for hepatocellular carcinoma (HCC) associated with acceptable rates of toxicity in appropriately selected patients. Despite often being reserved for patients unsuitable for other local treatments, prospective and retrospective studies have demonstrated excellent long-term control. SBRT may be used as a stand-alone treatment, or as an adjunct to other HCC therapies. Based on available data, SBRT appears to complement existing local liver therapies.Randomised and non-randomized comparative studies are required to better determine the optimal role of SBRT in HCC treatment.

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Section: Sbrt and Sorafenibmentioning

confidence: 99%

Advances in Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

Murray

Dawson

2017

Seminars in Radiation Oncology

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“…The low survival rate of monotherapy and the treatment resistance found in HCC might be overcome if combination therapy is adopted. Recently, clinical trials of combination of sorafenib and radiotherapy in HCC have been conducted, and better treatment results with high toxicity were found [22–24]. Treatment resistance found in HCC has been shown to be related to NF-κB activation [25, 26], which is involved in tumor invasiveness, metastasis, proliferation and antiapoptosis, all contribute to the malignancy of cancer cells [27, 28].…”

Section: Introductionmentioning

confidence: 99%

Sorafenib pretreatment enhances radiotherapy through targeting MEK/ERK/NF-κB pathway in human hepatocellular carcinoma-bearing mouse model

et al. 2016

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Patients with unresectable hepatocellular carcinoma (HCC) usually have poor prognosis because current monotherapy including surgery, chemotherapy and radiotherapy (RT) are not effective. Combination therapy may be effective to overcome this clinical problem. Here, we proposed the combination of sorafenib and RT, which have been applied in HCC treatment, could improve the treatment outcome of HCC. Our previous study showed that sorafenib could suppress the expression of NF-κB which is related to the chemo- and radio-resistance. Nevertheless, the expression of NF-κB is oscillatory and is affected by the treatments. Thus, understanding the oscillation of NF-κB expression would be beneficial for determining the optimal treatment schedule in combination therapy. Here established Huh7/NF-κB-tk-luc2/rfp cell line, in which NF-κB indicates a NF-κB promoter, was utilized to noninvasively monitor the expression of NF-κB overtime in vitro and in vivo. The results show that pretreatment of sorafenib with RT suppresses the expressions of NF-κB and its downstream proteins induced by radiation through downregulation of phosphorylated extracellular signal-regulated kinase (pERK) most significantly compared with other treatment schedules. The results were further verified with Western blotting, EMSA, and NF-κB molecular imaging. These findings suggest that pretreatment of sorafenib with RT may be the ideal treatment schedule for the treatment of HCC.

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“…SRS did neither alter the adverse effect profile of the underlying anti-angiogenic therapy nor induce other adverse events. Brade et al [32] evaluated sorafenib and SRT of intrahepatic HCC. Sixteen patients were treated with 2 sorafenib dose levels.…”

Section: Resultsmentioning

confidence: 99%

Radiotherapy and Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitors in Renal Cancer

et al. 2018

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Treatment of metastatic renal cell carcinoma (mRCC) has seen substantial progress over the last decade. A number of targeted therapies have been shown to improve clinical outcome. Vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitors (TKIs) are an effective option in treating mRCC. RCC is traditionally perceived to be a radioresistant malignancy with a limited role of radiotherapy (RT) in the management of localized disease. While RCC appears to be radioresistant using conventionally fractionated RT, preclinical data suggest increased radiosensitivity when an ablative, hypofractionated schedule is used. RT is a common treatment for metastases; therefore, it is important to understand how best to use the combination of RT with targeted therapies. Preclinical studies have suggested that the combination of anti-angiogenic drugs with RT enhances the therapeutic effect compared with ionizing radiation alone. However, clinical data gave rise to warnings due to an increased incidence of severe gastrointestinal side effects. This article reviews the literature behind the preclinical and clinical data of the combination of RT with VEGFR-TKIs currently approved for RCC (sunitinib, sorafenib, pazopanib, and axitinib), with a focus on dose schedules as well as efficacy and toxicity.

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Phase 1 Trial of Sorafenib and Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

Cited by 96 publications

References 17 publications

Advances in Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

Advances in Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

Sorafenib pretreatment enhances radiotherapy through targeting MEK/ERK/NF-κB pathway in human hepatocellular carcinoma-bearing mouse model

Radiotherapy and Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitors in Renal Cancer

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