Treatment of Hepatocellular Carcinoma Combining Sorafenib and Transarterial Locoregional Therapy: State of the Science

Weintraub, Joshua; Salem, Riad

doi:10.1016/j.jvir.2013.01.494

Cited by 35 publications

(21 citation statements)

References 50 publications

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“…It is also interesting that, among the patients who received combination treatment, six cases (20.6%) showed increased levels of skeletal muscle mass during this study, whereas only one case (9.1%) showed this phenomenon in the group of patients who were treated with sorafenib alone. Combined treatment with sorafenib and TACE has a strong scientific rationale because the ischemia that is induced by TACE results in local and systemic increases in vascular endothelial growth factor (VEGF), whereas sorafenib inhibits the activity of the VEGF receptor [24]. Several meta-analyses have shown a positive outcome in HCC patients treated with TACE and sorafenib, as compared with HCC patients treated with TACE alone [25,26,27].…”

Section: Discussionmentioning

confidence: 99%

Skeletal Muscle Depletion Predicts the Prognosis of Patients with Hepatocellular Carcinoma Treated with Sorafenib

Imai

Koji

Hanai

et al. 2015

IJMS

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The aim of this study was to determine whether skeletal muscle depletion predicts the prognosis of patients with hepatocellular carcinoma (HCC) that is being treated with sorafenib. We evaluated 40 consecutive HCC patients who received sorafenib treatment. The skeletal muscle cross-sectional area was measured by computed tomography at the third lumbar vertebra (L3), from which the L3 skeletal muscle index (L3 SMI) was obtained. The factors contributing to overall survival, sorafenib dose reduction, and discontinuation of sorafenib were analyzed using the Cox proportional hazards model. L3 SMI (p = 0.020) and log (α-fetoprotein (AFP)) (p = 0.010) were identified as independent prognostic factors in HCC patients treated with sorafenib. The initial dose of sorafenib (p = 0.008) was an independent risk factor for sorafenib dose reduction, and log (AFP) (p = 0.008) was the only significant risk factor for the discontinuation of this drug. L3 SMI was not a risk factor for either dose reduction (p = 0.423) or the discontinuation (p = 0.132) of sorafenib. A multiple linear regression analysis determined the following relationship between skeletal muscle mass (assessed as L3 SMI) and the explanatory factors: L3 SMI = −0.1896 × (Age) − 10.3441 × (Child-Pugh score) − 9.3922 × (log (AFP)) + 1.6139 × (log (AFP)) × (Child-Pugh score) + 112.9166. Skeletal muscle depletion is inversely associated with age, Child-Pugh score, and log (AFP). Moreover, it is an independent prognostic factor for HCC patients treated with sorafenib.

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Section: Discussionmentioning

confidence: 99%

Skeletal Muscle Depletion Predicts the Prognosis of Patients with Hepatocellular Carcinoma Treated with Sorafenib

Imai

Koji

Hanai

et al. 2015

IJMS

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“…This observed phenomenon is correlated to poor patient outcomes. As a result, with the approval of sorafenib (a multikinase inhibitor that targets VEGFR [10, 11] for HCC in 2007, several clinical trials have investigated the efficacy of combining oral systemic administration of sorafenib with TACE in order to address the observed pro-angiogenic response [12, 13]. …”

Section: Introductionmentioning

confidence: 99%

Poly(lactide-co-glycolide) microspheres for MRI-monitored delivery of sorafenib in a rabbit VX2 model

et al. 2015

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Transcatheter arterial embolization and chemoembolization are standard locoregional therapies for hepatocellular carcinoma (HCC). However, these can result in tumor hypoxia, thus promoting tumor angiogenesis. The anti-angiogenic agent sorafenib is hypothesized to improve outcomes; however, oral administration limits patient tolerance. Therefore, the purpose of this study was to fabricate poly(lactide-co-glycolide) microspheres for local sorafenib delivery to tumors during liver-directed embolotherapies. Iron oxide nanoparticles (IONP) were co-encapsulated for magnetic resonance imaging (MRI) of microsphere delivery. Microspheres were fabricated using a double emulsion/solvent evaporation method and characterized for size, sorafenib and IONP content, and MRI properties. MRI was performed before and after intra-arterial microsphere infusions in a rabbit VX2 liver tumor model. The microspheres were 13 microns in diameter with 8.8% and 0.89% (w/w) sorafenib and IONP, respectively. 21% and 28% of the loaded sorafenib and IONP, respectively, released within 72 hours. Rabbit VX2 studies demonstrated that sorafenib microspheres normalized VEGFR 2 activity and decreased microvessel density. Quantitative MRI enabled in vivo visualization of intra-hepatic microsphere distributions. These methods should avoid systemic toxicities, with MRI permitting follow-up confirmation of microsphere delivery to the targeted liver tumors.

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“…There are more than 20 clinical trials in progress evaluating locoregional treatments combined with molecular-targeted agents, and some have demonstrated promising results [140][141][142] . A large phase Ⅲ, randomized, placebo-controlled trial (the STORM trial) evaluating sorafenib as an adjuvant therapy after curative treatment (resection or local ablation) is ongoing [143] .…”

Section: Sorafenib and Locoregional Treatmentmentioning

confidence: 99%

Recent advances in multidisciplinary management of hepatocellular carcinoma

Gomaa¹

2015

WJH

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Treatment of Hepatocellular Carcinoma Combining Sorafenib and Transarterial Locoregional Therapy: State of the Science

Cited by 35 publications

References 50 publications

Skeletal Muscle Depletion Predicts the Prognosis of Patients with Hepatocellular Carcinoma Treated with Sorafenib

Skeletal Muscle Depletion Predicts the Prognosis of Patients with Hepatocellular Carcinoma Treated with Sorafenib

Poly(lactide-co-glycolide) microspheres for MRI-monitored delivery of sorafenib in a rabbit VX2 model

Recent advances in multidisciplinary management of hepatocellular carcinoma

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