Search results for "Phenylurea Compounds"
showing 10 items of 93 documents
Transarterial chemoembolization and sorafenib in hepatocellular carcinoma
2014
Transarterial chemoembolization (TACE) is considered as the standard therapy for patients with intermediate-stage hepatocellular carcinoma. However, given the high heterogeneity of this population, no common strategy or protocol standardization has been defined yet. In the last few years TACE treatment has been combined with sorafenib systemic therapy, reporting overall positive results both in terms of safety and efficacy. This systematic review presents and critically discusses the evidence available on the use of TACE in combination (concomitant or sequential) with sorafenib, focusing also on clinical trials currently ongoing to better define an optimal therapeutic strategy for this grou…
Is the efficacy of sorafenib treatment in patients with hepatocellular carcinoma affected by age?
2013
Cancer is a prevalent disease in the elderly population and hepatocellular carcinoma (HCC) is a major health problem among all tumors. Curative treatments for early-stage include liver transplantation, resection and percutaneous ablation. Transarterial chemoembolization (TACE) and sorafenib, classified as non-curative treatments, can improve survival for patients with intermediate and advanced tumors, respectively. Even if the incidence of HCC progressively increases with advanced age in all populations, reaching a peak at 70 years, few reports concerning correct management of HCC in elderly patients exist. Moreover, data from large randomized controlled trials (RCT) poorly reflect the elde…
Heterogeneity of Patients with Intermediate (BCLC B) Hepatocellular Carcinoma: Proposal for a Subclassification to Facilitate Treatment Decisions
2013
The intermediate stage of hepatocellular carcinoma (HCC) comprises a highly heterogeneous patient population and therefore poses unique challenges for therapeutic management, different from the early and advanced stages. Patients classified as having intermediate HCC by the Barcelona Clinic Liver Cancer (BCLC) staging system present with varying tumor burden and liver function. Transarterial chemoembolization (TACE) is currently recommended as the standard of care in this setting, but there is considerable variation in the clinical benefit patients derive from this treatment.In April 2012, a panel of experts convened to discuss unresolved issues surrounding the application of current guidel…
Survival of patients treated with sorafenib for hepatocellular carcinoma recurrence after liver transplantation: A systematic review and meta-analysis
2014
Background: Data on survival and safety of sorafenib for hepatocellular carcinoma recurrence after liver transplant are still equivocal. Aim: We performed a meta-analysis of published studies, with the aim of estimating the 1-year rates of survival, analysing the variability in survival rates and, finally, identifying the factors associated with a longer survival. Methods: Data from 8 of the 17 selected studies were pooled, while the other 9 were excluded because survival rates were missing. All included studies were retrospective. Results: Overall, the 1-year survival ranged from 18% to 90%. Tumour progression was the main cause of death. The second cause was bleeding, reported only in pat…
Extrahepatic spread of hepatocellular carcinoma
2012
Hepatocellular carcinoma (HCC) is a major health problem. The treatment of HCC depends on the tumour stage and on the severity of underlying cirrhosis, however, a majority of HCC patients have advanced disease at presentation. In recent years extra-hepatic spread (ES) of HCC seems to have been observed more frequently than in the past even if few data exist in literature on prevalence, clinical presentation and prognosis of patients with HCC ES. Aim of this brief review is underline the main concerns, pitfalls and warnings in practicing with these patients. ES of HCC are not rare, and the probability of finding ES is higher in patients with advanced intra-hepatic HCC. The more frequent ES s…
Galactosylated polymeric carriers for liver targeting of sorafenib
2014
In this paper, we describe the preparation of liver-targeted polymeric micelles potentially able to carry sorafenib to hepatocytes for treatment of hepatocarcinoma (HCC), exploiting the presence of carbohydrate receptors, ASGPR. These micelles were prepared starting from a galactosylated polylactide-polyaminoacid conjugate. This latter was obtained by chemical reaction of α,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-d,l-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, leading to PHEA-EDA-PLA-GAL copolymer. Liver-targeted sorafenib-loaded micelles were obtained in aqueous media at low PHEA-EDA-PLA-GAL copolymer concentration value with nanometer …
Lipid nanocarriers containing sorafenib inhibit colonies formation in human hepatocarcinoma cells
2015
Here, the potential of two nanostructured lipid carriers (NLC) for controlled release of sorafenib was evaluated. The obtained systems showed characteristics suitable as drug delivery systems for the treatment of hepatocellular carcinoma (HCC) through parenteral administration. The use of a mixture between a solid lipid (tripalmitin) with a liquid lipid (Captex 355 EP/NF or Miglyol 812) to prepare NLC systems could give a higher drug loading capacity and a longer term stability during storage than that obtained by using only solid lipids. The obtained nanoparticles showed a nanometer size and high negative zeta potential values. Scansion electron microscopy (SEM) of the sorafenib loaded NLC…
Sorafenib, but not sunitinib, affects function of dendritic cells and induction of primary immune responses
2008
AbstractThe tyrosine kinase inhibitors sorafenib and sunitinib are approved for the treatment of patients with malignant diseases. To analyze the possible use of these compounds in combination with immunotherapeutic approaches, we analyzed the effects of both inhibitors on the immunostimulatory capacity of human dendritic cells (DCs) and the induction of primary immune responses in vivo. Sorafenib, but not sunitinib, inhibits function of DCs, characterized by reduced secretion of cytokines and expression of CD1a, major histocompatibility complex, and costimulatory molecules in response to TLR ligands as well as by their impaired ability to migrate and stimulate T-cell responses. These inhib…
Novel inhibitors in development for hepatocellular carcinoma
2010
The multikinase inhibitor sorafenib was the first agent to demonstrate a survival benefit for patients with locally advanced or metastatic hepatocellular carcinoma (HCC). Although sorafenib represents a landmark in the treatment of HCC and proved molecularly targeted therapy to be effective in this disease, it represents just the first step towards an improvement in systemic therapy. Since then, novel inhibitors have been evaluated in early clinical trials, showing potential activity.This article aims to review novel inhibitors emerging in the field of advanced HCC. An Internet-based search was performed to identify abstracts, clinical trials ( www.clinicaltrials.gov , last accessed 30 Nove…
Targeted Therapies in Hepatocellular Carcinoma
2014
Abstract: The onset of hepatocellular carcinoma (HCC) is related to the development of non-neoplastic liver disease, such as viral infections and cirrhosis. Even though patients with chronic liver diseases undergo clinical surveillance for early diagnosis of HCC, this cancer is often diagnosed in advanced stage. In this case locoregional treatment is not possible and systemic therapies are the best way to control it. Until now sorafenib, a Raf and multi-kinase inhibitor has been the best, choice to treat HCC systemically. It showed a survival benefit in multicenter phase III trials. However the proper patient setting to treat is not well defined, since the results in Child-Pugh B patients a…