Safety and effectiveness of sorafenib in patients with hepatocellular carcinoma in clinical practice
ABSTRACT Sorafenib is currently the only approved systemic treatment for hepatocellular carcinoma.
to evaluate safety and effectiveness of sorafenib in the field of practice.
We report a single-centre experience on 116 advanced hepatocellular carcinoma patients treated with sorafenib between February 2008 and March 2011. Every 4 weeks, adverse events were graded using Common Toxicity Criteria version 3.0, and every 3 months tumour response was assessed according to modified Response Evaluation Criteria in Solid Tumours for hepatocellular carcinoma.
Cirrhosis was present in 95.7% of patients (83.6% Child-Pugh A class), hepatitis C was the main etiological factor. Median therapy duration was 3 months and median daily dose was 642 mg. Median time-to-radiological progression in the per-protocol population was 12 months and median overall survival in the intention-to-treat population was 13 months. 91.4% of patients experienced mild adverse events (grade 1 or 2), the most frequent were gastrointestinal and dermatological. Jaundice and bleeding were the main causes of definitive drug discontinuation. 3-month overall disease control rate was 70.6%: stable disease in 37.2%, partial response in 30.8%, and complete response in 2.6% patients. The 3-month radiological response correlated with overall survival.
In daily clinical practice, sorafenib confirmed its safety and efficacy in hepatocellular carcinoma patients.
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ABSTRACT: The development of hepatocellular carcinomas from malignant hepatocytes is frequently associated with intra- and peritumoral accumulation of connective tissue arising from activated hepatic stellate cells (HSC). Inhibition of receptor tyrosine kinase (RTK) signaling showed promise in the treatment of hepatocellular carcinoma. However, there is a lack of knowledge about the effects of RTK inhibitors on the tumor supportive cells. We performed in vitro experiments to study whether Sunitinib, a Platelet-Derived Growth Factor (PDGF) and Vascular Endothelial Growth Factor (VEGF) RTKs' inhibitor, could block both activated HSC functions and angiogenesis and thus prevent the progression of cirrhotic liver to hepatocellular carcinoma. In immortalized human activated HSC LX-2, treatment with Sunitinib 100nM blocked collagen synthesis by 47%, as assessed by Sirius Red staining, attenuated HSC contraction by 65%, and reduced cell migration by 28% as evaluated using a Boyden's Chamber, without affecting cell viability, measured by Trypan blue staining, and apoptosis, measured by Propidium Iodide (PI) incorporation assay. Our data revealed that Sunitinib treatment blocked the transdifferentiation of primary human HSC (hHSC) to activated myofibroblast-like cells by 65% without affecting hHSC apoptosis and migration. In in vitro angiogenic assays, Sunitinib 100nM reduced Endothelial Cells (EC) ring formation by 46% and tube formation by 68%, and decreased vascular sprouting in aorta ring assay and angiogenesis in vascular bed of chick embryo. In conclusion, the present study demonstrates that the RTK inhibitor Sunitinib blocks the activation of HSC and angiogenesis suggesting its potential as a drug candidate in pathological conditions like liver fibrosis and hepatocellular carcinoma.European journal of pharmacology 02/2013; 705(1-3). DOI:10.1016/j.ejphar.2013.02.026 · 2.68 Impact Factor
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ABSTRACT: Many non-surgical treatments of hepatocellular carcinoma (HCC) have significantly improved in the last few decades and have shown survival benefits for selected patients with HCC. Today ablation can improve survival in individuals diagnosed in early HCC and even offer a curative treatment in selected candidates. Patients with intermediate-stage HCC benefit from transarterial chemoembolization (TACE). Drug-eluting bead transarterial chemoembolization (DEB-TACE) has shown a better combined ischemic and cytotoxic effect locally and less system toxicity when compared with conventional TACE. Those diagnosed at advanced stage benefit from sorafenib. In addition to TACE and sorafenib which could improve survival for selected patients, three-dimensional conformal radiotherapy treatment (3-DCRT), selection internal radiation therapy and systemic chemotherapy have also shown anti-tumor activity in the treatment of advanced HCC, but their survival benefit have not been proven. The limited effects of single therapy suggested that the combination would enhance the overall treatment effect. Other potential non-surgical therapies like gene therapy and immunotherapy are still in testing phases, except for some small-scale clinical trials which have been reported to show some beneficial effect. Here, we review the current non-surgical treatments in HCC and the new advances in this field.Medical Oncology 03/2013; 30(1):381. DOI:10.1007/s12032-012-0381-y · 2.06 Impact Factor
- Digestive and Liver Disease 04/2013; 45(5). DOI:10.1016/j.dld.2013.02.018 · 2.89 Impact Factor