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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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[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.
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What is the indication for sorafenib in hepatocellular carcinoma? A clinical challenge.
Kim, R, Byrne, MT, Tan, A, Aucejo, F
Oncology (Williston Park, N.Y.). 2011;(3):283-91, 295
Abstract
The incidence of hepatocellular carcinoma is rising in many countries, including the United States. Approval of sorafenib (Nexavar) as the first targeted therapy for treatment of advanced hepatocellular carcinoma (HCC) represents a milestone in the treatment of this disease. The approval was based on two large randomized phase III trials from the Western and Eastern hemispheres that showed an overall survival benefit compared with placebo in patients with well-preserved liver function. The exact indication for sorafenib is unclear, however. The U.S. Food and Drug Administration (FDA) authorized use of sorafenib for "unresectable HCC", an indication which is very broad, vague, and confusing. Less is known about the effects of sorafenib in patients with decompensated liver disease, or of sorafenib in combination with local therapy or in a transplant setting. Prospective trials are lacking in these areas. We will review current data on use of sorafenib in HCC.
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4.
Sorafenib for HCC: a pragmatic perspective.
Razumilava, N, Gores, GJ
Oncology (Williston Park, N.Y.). 2011;(3):300, 302
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Advanced hepatocellular carcinoma. Review of targeted molecular drugs.
Alves, RC, Alves, D, Guz, B, Matos, C, Viana, M, Harriz, M, Terrabuio, D, Kondo, M, Gampel, O, Polletti, P
Annals of hepatology. 2011;(1):21-7
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world in terms of incidence, accounting for approximately 630 thousand new cases per year; in addition, HCC is the third most common cause of cancer death. Worldwide, the greatest risk factors for HCC are the infections caused by hepatitis B and C viruses, which increase the risk of developing the disease by about 20 times. The standard treatment in the early stages of the disease, such as surgical resection, local ablation and liver transplantation, are able to cure a proportion of patients, but most cases of HCC present in advanced stages, precluding the use of such treatments with curative intent. In these advanced stages, systemic treatments are commonly used. Unfortunately, chemotherapy with conventional cytotoxic agents is ineffective and does not seem to modify the natural history of disease. Treatment options for patients with advanced HCC are extremely limited, but the identification of signaling pathways, and the recognition of the role of these pathways in the pathogenesis of the disease resulted in the development of drugs directed at specific therapeutic targets. One such drug is Sorafenib, a kinase inhibitor with antiangiogenic and antiproliferative properties. In conclusion, Sorafenib has demonstrated survival benefits in patients with advanced HCC, thus representing a new standard reference for systemic treatment in these cases.
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6.
[Current aspects of second-line and sequence therapy of metastatic renal cell carcinoma].
Gschwend, JE
Onkologie. 2010;:10-1
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Abstract
The treatment objective in the metastatic situation is to delay progression while maintaining the best possible quality of life. Since several targeted therapies with different modes of action already exist, sequence therapy is increasingly being considered. Current data regarding sequential treatment is still insufficient and several approaches are being tested in ongoing clinical studies. Based on current data, guidelines, and the therapeutic algorithms supported by national and international professional associations, the German Cancer Society's interdisciplinary task force on renal cell carcinoma (RCC) recommends the following approach: since the efficacy of cytokines is very limited after a previous cytokine-based therapy has failed, Sorafenib or Sunitinib are the treatment of choice. Treatment with other targeted substances is recommended after first-line therapy has failed as a number of retrospective studies have documented relevant activity. Everolimus currently is the treatment of first choice when VEGF-directed therapy has failed. Based on the results of phase II studies, other tyrosine kinase inhibitors can alternatively be applied.
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Downstaging of hepatocellular carcinoma prior to liver transplant: is there a role for adjuvant sorafenib in locoregional therapy?
Vagefi, PA, Hirose, R
Journal of gastrointestinal cancer. 2010;(4):217-20
Abstract
Hepatocellular carcinoma (HCC) remains a common cause of mortality worldwide. Liver transplantation has emerged as the optimal treatment for cirrhotic patients with HCC; however, the shortage of donor organs leaves waitlisted patients at risk for disease progression beyond transplant criteria. Prevention of waitlist dropout has fueled investigation into a wide array of locoregional therapies for the management of HCC in candidates awaiting liver transplantation. We present a patient with HCC who underwent treatment with sorafenib, which resulted in a remarkable reduction in tumor burden to allow for liver transplant listing.
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Sorafenib: where do we go from here?
Siegel, AB, Olsen, SK, Magun, A, Brown, RS
Hepatology (Baltimore, Md.). 2010;(1):360-9
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Abstract
The approval of sorafenib as the first effective drug for the treatment of hepatocellular carcinoma (HCC) represents a milestone in the treatment of this disease. A better understanding of HCC pathogenesis has led to the development of several novel targeted treatments. HCC is treated in a uniquely multidisciplinary way requiring surgeons, hepatologists, interventional radiologists, and oncologists. This review describes the molecular pathogenesis of HCC, explores current and future treatments based on these pathways, and describes how these new therapies may augment existing approaches to HCC treatment.
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[Interferon alpha and half-dose sorafenib is an effective treatment modality for interferon alpha-resistant metastatic renal cell carcinoma: a case report].
Furuya, N, Kamai, T, Tokui, N, Abe, H, Fukabori, Y, Yoshida, K
Hinyokika kiyo. Acta urologica Japonica. 2009;(6):323-6
Abstract
Metastatic renal cell carcinoma is notoriously resistant to chemotherapy and radiotherapy. Immunotherapy with interferon alpha is widely used for the disease, but its treatment effects are poor. A 69-year-old Japanese women presented with gross hematuria. Imaging studies revealed a left renal tumor, 12 cm in diameter, and multiple pulmonary and hepatic lesions. No abnormal laboratory data were observed other than anemia with Hb 9.2 g/dl. Performance status was 0. She underwent radial left nepherectomy. Pathological examination showed clear cell renal cell carcinoma with moderate histological differentiation (grade 2) and microscopic vessel invasion; pT3aN0M1 (Pul, Hep). Memorial Sloon-Kettering Cancer Center classification was an intermediate risk due to anemia. She received interferon alpha, 5 million IU three times per week, postoperatively. In three months, hepatic lesions rapidly progressed although there was no interval change of pulmonary lesions. Then, the patient received interferon alpha at the same dose as described above and half-dose sorafenib, 400 mg per day. Grade 2 hypertension was under control by calcium channel blocker and the hand-foot syndrome was not obvious. No other grade 3/4 drug-related adverse events were observed. In one month after combination therapy, not only pulmonary lesions but also hepatic lesions were smaller. She has received this combination therapy with stable disease for six months. Performance status was 1 with grade 1 fatigue. The doses of this regimen may be tolerable, and might be an available treatment option for interferon alpha-resistant advanced renal cancer.
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10.
Sorafenib, a systemic therapy for hepatocellular carcinoma.
Méndez-Sánchez, N, Vásquez-Fernández, F, Zamora-Valdés, D, Uribe, M
Annals of hepatology. 2008;(1):46-51
Abstract
Hepatocellular carcinoma is a lethal disease that requires a multidisciplinary approach and management. Surgical therapy offers long-term survival; however, few patients are candidates. There has been no accepted systemic therapy for this disease until recently. This article briefly discusses the role of RAS/RAF/MEK/ERK signaling pathway in the pathogenesis of the disease and the promising role of sorafenib for advanced disease.