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Strategies for assessing and managing the adverse events of sorafenib and other targeted therapies in the treatment of renal cell and hepatocellular carcinoma: recommendations from a European nursing task group.
Edmonds, K, Hull, D, Spencer-Shaw, A, Koldenhof, J, Chrysou, M, Boers-Doets, C, Molassiotis, A
European journal of oncology nursing : the official journal of European Oncology Nursing Society. 2012;(2):172-84
Abstract
PURPOSE As a group of European nurses familiar with treating patients with renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) using targeted/chemo- therapies, we aimed to review strategies for managing adverse events (AEs) associated with one targeted therapy, sorafenib. METHOD Focusing on the AEs we considered the most difficult to manage (hand-foot skin reaction [HFSR], diarrhoea, fatigue and mucositis/stomatitis), we reviewed the literature to identify strategies relevant to sorafenib. Given the paucity of published work, this included strategies concerning targeted agents in general. This information was supplemented by considering the wider literature relating to management of these AEs in other tumour types and similar toxicities experienced during conventional anti-cancer therapy. Together with our own experience, this information was used to compile an AE management guide to assist nurses caring for patients receiving sorafenib. RESULTS Our collated experience suggests the most commonly reported AEs with sorafenib and other targeted agents are HFSR, diarrhoea, fatigue, rash and mucositis/stomatitis; these generally have an acute (appearing at ∼0-1 months) or delayed onset (appearing at ∼3 months). Most management strategies in the literature were experience-based rather than arising from controlled studies. However, strategies based on controlled studies are available for HFSR and mucositis/stomatitis. CONCLUSIONS Evidence, especially from controlled studies, is sparse concerning management of AEs associated with sorafenib and other targeted agents in RCC/HCC. However, recommendations can be made based on the literature and clinical experience that encompasses targeted and conventional therapies, particularly in the case of non-specific toxicities e.g. diarrhoea and fatigue.
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Sorafenib (BAY 43-9006) in hepatocellular carcinoma patients: from discovery to clinical development.
Ranieri, G, Gadaleta-Caldarola, G, Goffredo, V, Patruno, R, Mangia, A, Rizzo, A, Sciorsci, RL, Gadaleta, CD
Current medicinal chemistry. 2012;(7):938-44
Abstract
Angiogenesis and signaling through the RAS/RAF/mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK cascade have been reported to play important roles in the development of hepatocellular carcinoma (HCC). Sorafenib (Nexavar), a novel bi-aryl urea BAY 43-9006, is an orally administered multikinase inhibitor with activity against RAS/RAF kinases multikinase inhibitor with activity against RAF kinases and several receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), FLT3, Ret, and c-Kit. It is involved in angiogenic pathway and cell proliferation. Sorafenib has demonstrated potent anti-tumor activity in in vitro studies, preclinical xenograft models of different tumor types and human clinical trials. This review summarizes the history of sorafenib from its discovery by the medicinal chemistry approach through to clinical development and ongoing trials on the combination between sorafenib and trans-arterial chemoembolization (TACE) in HCC patients.
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3.
Are there opportunities for chemotherapy in the treatment of hepatocellular cancer?
Asghar, U, Meyer, T
Journal of hepatology. 2012;(3):686-95
Abstract
Hepatocellular cancer is a significant global health problem yet the prognosis for the majority of patients has not changed significantly over the past few decades. For patients with advanced disease, sorafenib is currently the standard of care providing a survival advantage of 2-3 months in selected patients. Cytotoxic chemotherapy has been used for over 30 years but definite evidence that it prolongs survival has been lacking. Resistance remains a significant barrier for both targeted and cytotoxic agents and an understanding of the underlying mechanisms is critical if outcomes are to be improved. Here, we summarise the past and current data that constitute the evidence base for chemotherapy in HCC, review the causes of chemoresistance and suggest strategies to overcome these barriers.
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Advanced HCC: emerging molecular therapies.
Finn, RS
Minerva gastroenterologica e dietologica. 2012;(1):25-34
Abstract
Hepatocellular carcinoma (HCC) is a common complication of chronic liver disease and represents the third-leading cause of death world-wide. While the majority of cases occur in Asia, the incidence has been rising in the West for some time. This is driven not only by the Hepatitis C epidemic but also the rising incidence of non-alcoholic steatohepatitis and resulting liver disease. Despite its frequency, treatments for HCC have generally been limited. Curative treatments are limited to surgical resection or liver transplant for a subset of patients and locally ablative techniques such as radiofrequency ablation (RFA) and trans-arterial chemoembolization (TACE) have been shown to extend survival for patients with unresectable and intermediate stage liver cancer. For patients with advanced HCC, sorafenib, a small molecule multitargeted kinase inhibitor is the only agent that has been shown to improve survival. At this time there is an abundance of research activity in HCC with an emphasis on developing new agents that target specific molecular alterations in HCC. In this review, we will focus on those agents currently in Phase III studies for front-line, second-line and other indications.
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Management of hepatocellular carcinoma: beyond sorafenib.
Chan, SL, Mok, T, Ma, BB
Current oncology reports. 2012;(3):257-66
Abstract
The positive results of sorafenib have unveiled a new direction of research in the management of hepatocellular carcinoma (HCC). Since then intensive efforts have been focused on development of novel management strategy to further improve the outcome for patients with HCC. Emerging data have suggested that tumor progression of HCC is driven by a number of deregulated signaling pathways and/or epigenetic mechanism. Thus much effort is dedicated to identification of novel agents targeting these dysregulated pathways. Combinations of targeted therapeutics and transarterial chemoembolization (TACE), or different systemic therapeutics also hold the promise to improve treatment outcome beyond sorafenib. This review aims to summarize the current status of clinical development of treatment in HCC. Perspectives on future direction of research will also be discussed.
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6.
Novel molecular therapies in hepatocellular carcinoma.
Faivre, S, Bouattour, M, Raymond, E
Liver international : official journal of the International Association for the Study of the Liver. 2011;:151-60
Abstract
The approval of sorafenib as the standard of care (SOC) for advanced hepatocellular carcinoma (HCC) fostered interest to further evaluate several other targeted therapies and extend the positioning of sorafenib alone and in combination with other drugs and local therapies at earlier stages and in an adjuvant setting. This review highlights current research using targeted therapies in HCC. Information for this review was compiled by searching PubMed and MEDLINE databases for articles published until September 2010. Several small molecules and humanized antibodies with anti-angiogenic and antiproliferative properties are currently being investigated in preclinical and/or clinical trials. Results are awaited from these clinical trials and offer promise for extending the current treatment options in HCC. Currently published data suggest that substantial progress may be achieved in the treatment of patients with HCC in the next 10 years.
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7.
Molecularly targeted therapies for hepatocellular carcinoma: sorafenib as a stepping stone.
Kim, HY, Park, JW
Digestive diseases (Basel, Switzerland). 2011;(3):303-9
Abstract
Since sorafenib, a multikinase inhibitor targeting angiogenesis of hepatocellular carcinoma (HCC), demonstrated survival benefits in recent clinical trials, it has changed the treatment paradigm and become the standard first-line treatment for patients with advanced HCC. However, disease stabilization with sorafenib lasts a few months, possibly due to the development of resistance, and thus the survival advantage was modest, even in patients with preserved liver function. Furthermore, there is currently no biomarker for monitoring the response or resistance to sorafenib. Currently, various kinds of molecularly targeted agents have been developed and are being evaluated in clinical trials. There are several steps required to improve the outcome from sorafenib therapy. First, a reliable predictive and prognostic biomarker is urgently needed. Second, a compelling indication of sorafenib treatment for HCC needs more clinical studies and consensus. Third, the actual benefits of sorafenib to patients with advanced liver dysfunction should be clarified and a more effective strategy for targeted therapy needs to be developed, for example, using a combination of targeted agents acting on different pathways or different levels of a key pathway. Finally, sorafenib could be used with other treatment modalities, such as local ablation or transarterial chemoembolization, to synergize efficacy. Based on the successful introduction of sorafenib, future studies should focus on plans to further improve the outcome of HCC patients by overcoming resistance and maximizing the efficacy of molecularly targeted therapy.
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t(8;22)/BCR-FGFR1 myeloproliferative disorder presenting as B-acute lymphoblastic leukemia: report of a case treated with sorafenib and review of the literature.
Wakim, JJ, Tirado, CA, Chen, W, Collins, R
Leukemia research. 2011;(9):e151-3
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9.
Candidacy for sorafenib in HCC patients: is there a slippery slope beyond a SHARP edge?
Burak, KW
Oncology (Williston Park, N.Y.). 2011;(3):296, 298, 300
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10.
[Myocardial metastasis from renal cell carcinoma treated with sorafenib].
Tokuyama, Y, Iwamura, M, Fujita, T, Sugita, A, Maeyama, R, Bessho, H, Ishikawa, W, Tabata, K, Yoshida, K, Baba, S
Hinyokika kiyo. Acta urologica Japonica. 2011;(10):555-8
Abstract
We present a case of myocardial metastasis from renal cell carcinoma (RCC) during the treatment with sorafenib. A 63-year-old male, who had undergone right radical nephrectomy, received interferon-alpha (IFN), interleukin (IL-2) and 5-flurouracil (5-FU) for the treatment of lung and pleural metastases. However, since this metastasis showed progressive disease, we administered sorafenib. Nine months after the introduction of sorafenib, he complained of dyspnea. Chest computed tomography and cardiac ultrasonography revealed a low density mass at the cardiac muscle of the left cardiac ventricle, suggesting myocardial metastasis of RCC. Molecular targeted therapy achieved a longer survival in advanced RCC patients in comparison with the immunotherapy using cytokines. Therefore, in metastasis evaluation, some organs which have been regarded as rare sites should be carefully evaluated.