Vandetanib in patients with inoperable hepatocellular carcinoma: A phase II, randomized, double-blind, placebo-controlled study

Hsu, Chiun; Yang, Tsung‐Ming; Huo, Teh Ia; Hsieh, Ruey Kuen; Yu, Chih Wei; Hwang, Wei Shou; Hsieh, Tsai Yuan; Huang, Wen-Cheng; Chao, Yee; Meng, Robin; Cheng, Ann‐Lii

doi:10.1016/j.jhep.2011.12.013

Cited by 91 publications

(71 citation statements)

References 31 publications

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“…One such multikinase inhibitor, vandetanib, was reported in patients with advanced HCC [34]. Out of 44 patients treated with vandetanib, there were no objective responders and 5 patients with disease stabilization for longer than 4 months.…”

Section: Discussionmentioning

confidence: 99%

Bevacizumab with Erlotinib as First-line Therapy in Asian Patients with Advanced Hepatocellular Carcinoma: A Multicenter Phase II Study

Hsu¹,

Kang

Yang

et al. 2013

Oncology

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Objectives: The bevacizumab/erlotinib combination was reported with high clinical activity for advanced hepatocellular carcinoma (HCC) by a phase II study conducted in the USA. This multicenter study across several Asian countries was to evaluate the safety and efficacy of the combination in this population. Methods: Patients with histology-proven HCC, advanced disease and Child-Pugh class A liver function received bevacizumab 5 mg/kg intravenously every 2 weeks and erlotinib 150 mg/day orally as first-line therapy. The primary end point was progression-free survival at 16 weeks (PFS-16W). The expression of epidermal growth factor receptor (EGFR), phospho-AKT and vascular endothelial growth factor, the microvessel density and the EGFR gene copy number in HCC tissues were correlated with treatment efficacy. Results: Fifty-one patients were enrolled. The PFS-16W was 35.3% (95% CI 22.4-49.9), the median PFS was 2.9 months (95% CI, 1.3-4.4) and the median overall survival was 10.7 months (95% CI, 6.2-15.2). Grade 3/4 toxicities were uncommon, including rash, acne (10% each), diarrhea (6%) and gastrointestinal bleeding (4%). None of the evaluated biomarkers correlated with disease control or PFS. Conclusions: Bevacizumab plus erlotinib showed good tolerability and modest activity in this Asian cohort. Further studies are warranted to identify the predictive biomarkers of this combination.

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Section: Discussionmentioning

confidence: 99%

Bevacizumab with Erlotinib as First-line Therapy in Asian Patients with Advanced Hepatocellular Carcinoma: A Multicenter Phase II Study

Hsu¹,

Kang

Yang

et al. 2013

Oncology

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“…De Bruyne et al [127] 19 DCE-MRI AUC decrease CRC metastases Bevacizumab Vriens et al [129] 23 DCE-MRI K trans decrease CRC metastases Cytotoxic therapy Coenegrachts et al [130] 10 DCE-MRI Kep increase CRC metastases Bevacizumab + FOLFIRI Deckers et al [126] 20 DWI ADC decrease CRC metastases Chemotherapy Niwa et al [133] 63 DWI ADC decrease PDAC Gemcitabine Cuneo et al [134] 12 DWI ADC increase PDAC Chemoradiation Yao et al [135] 39 pCT BF decrease PanNET Bevacizumab ± everolimus Miyazaki et al [132] [115,116] .…”

Section: Primary Liver Tumorsmentioning

confidence: 99%

Prognostication and response assessment in liver and pancreatic tumors: The new imaging

Robertis¹,

Martini²,

Demozzi³

et al. 2015

WJG

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Diffusion-weighted imaging (DWI), dynamic contrastenhanced magnetic resonance imaging (DCE-MRI) and perfusion computed tomography (CT) are technical improvements of morphologic imaging that can evaluate functional properties of hepato-bilio-pancreatic tumors during conventional MRI or CT examinations. Nevertheless, the term "functional imaging" is commonly used to describe molecular imaging techniques, as positron emission tomography (PET) CT/MRI, which still represent the most widely used methods for the evaluation of functional properties of solid neoplasms; unlike PET or single photon emission computed tomography, functional imaging techniques applied to conventional MRI/CT examinations do not require the administration of radiolabeled drugs or specific equipments. Moreover, DWI and DCE-MRI can be performed during the same session, thus providing a comprehensive "one-step" morphological and functional evaluation of hepato-bilio-pancreatic tumors. Literature data reveal that functional imaging techniques could be proposed for the evaluation of these tumors before treatment, given that they may improve staging and predict prognosis or clinical outcome. Microscopic changes within neoplastic tissues induced by treatments can be detected and quantified with functional imaging, therefore these techniques could be used also for posttreatment assessment, even at an early stage. or altered cellular membranes will present diffusion restriction, which is depicted as signal hyperintensity areas on high b-value DW images and hypointensity on the apparent diffusion coefficient (ADC) maps; ADC measurement can also quantify water molecules' diffusion. As dedifferentiation or therapies may induce microscopic changes in neoplastic tissues that could modify water molecules' diffusion, DWI can distinguish between different degrees of malignancy and can be also proposed for post-treatment monitoring. Moreover, DWI can be performed in a single session with DCE-MRI, thus providing a comprehensive "one-step" morphological and functional evaluation of hepatobilio-pancreatic tumors.Perfusion imaging techniques evaluate changes in signal intensity (DCE-MRI) or density (pCT) after contrast medium injection, being therefore able to assess microvascularization through the evaluation of the dynamics of contrast medium distribution from vessels to the neoplastic tissue. Perfusion parameters are therefore theoretically good candidates for the evaluation of microscopic vascular differences between lesions with different pathological grade and for the assessment of treatment response, especially after chemoembolization or during treatments with antiangiogenic drugs.This editorial analyzes up-to-date literature data regarding the application of functional imaging techniques, apart from molecular imaging, to hepatic and pancreatic tumors, with particular emphasis on correlations to pathological features, prognostic stratification and therapeutic response assessment. FUNCTIONAL IMAGING TECHNIQUES: TECHNICAL BASESIn 1965 Stejskal and Tanne...

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“…Data from clinical trials on a variety of molecular targeted therapies for advanced HCC are shown in table 1[3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56]. …”

Section: Clinical Trials Of Molecular Targeted Therapy For Advanced Hccmentioning

confidence: 99%

Clinical Trials in Hepatocellular Carcinoma: An Update

et al. 2013

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The success of sorafenib has spurred an explosive increase of clinical trials testing novel molecular targets and other agents in the treatment of hepatocellular carcinoma (HCC). The paradigm of the studies has been characterized by three noticeable changes. First, the molecular targets of interest have expanded from angiogenesis to cancer cell-directed oncogenic signaling pathways for advanced HCC treatment. Agents targeting EGFR, FGFR, PI3K/Akt/mTOR, TGF-β, c-Met, MEK, IGF signaling, and histone deacetylase have been actively explored. Second, the target indication has shifted from advanced stage to early or intermediate stages of disease. The feasibility of combining locoregional therapies and targeted agents, and the use of novel agents after curative treatments are currently under active investigation. Finally, the therapeutic strategy has shifted from monotherapy to combination targeted therapy. We aim to provide a comprehensive overview of newly disclosed and ongoing clinical trials for the treatment of HCC.

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Vandetanib in patients with inoperable hepatocellular carcinoma: A phase II, randomized, double-blind, placebo-controlled study

Cited by 91 publications

References 31 publications

Bevacizumab with Erlotinib as First-line Therapy in Asian Patients with Advanced Hepatocellular Carcinoma: A Multicenter Phase II Study

Bevacizumab with Erlotinib as First-line Therapy in Asian Patients with Advanced Hepatocellular Carcinoma: A Multicenter Phase II Study

Prognostication and response assessment in liver and pancreatic tumors: The new imaging

Clinical Trials in Hepatocellular Carcinoma: An Update

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