Advanced hepatocellular carcinoma and sorafenib: Diagnosis, indications, clinical and radiological follow-up

Abstract

Advanced stage hepatocellular carcinoma (HCC) is a category of disease defined by radiological, clinical and hepatic function parameters, comprehending a wide range of patients with different general conditions. The main therapeutic option is represented by sorafenib treatment, a multi-kinase inhibitor with anti-proliferative and anti-angiogenic effect. Trans-arterial Radio Embolization also represents a promising new approach to intermediate/advanced HCC. Post-marketing clinical studies showed that only a portion of patients actually benefits from sorafenib treatment, and an even smaller percentage of patients treated shows partial/complete response on follow-up examinations, up against relevant costs and an incidence of drug related adverse effects. Although the treatment with sorafenib has shown a significant increase in mean overall survival in different studies, only a part of patients actually shows real benefits, while the incidence of drug related significant adverse effects and the economic costs are relatively high. Moreover, only a small percentage of patients also shows a response in terms of lesion dimensions reduction. Being able to properly differentiate patients who are responding to the therapy from non-responders as early as possible is then still difficult and could be a pivotal challenge for the future; in fact it could spare several patients a therapy often difficult to bear, directing them to other second line treatments (many of which are at the moment still under investigation). For this reason, some supplemental criteria to be added to the standard modified Response Evaluation Criteria in Solid Tumors evaluation are being searched for. In particular, finding some parameters (cellular density, perfusion grade and enhancement rate) able to predict the sensitivity of the lesions to anti-angiogenic agents could help in stratifying patients in terms of treatment responsiveness before the beginning of the therapy itself, or in the first weeks of sorafenib treatment. This would bring a strongly desirable help in clinical managements of these patients.

Evaluation of antiangiogenic and antiproliferative effects of sorafenib by sequential histology and intravoxel incoherent motion diffusion-weighted imaging in an orthotopic hepatocellular carcinoma xenograft model

“…Sorafenib is a multikinase inhibitor with antiangiogenic and antiproliferative effects and shows profound antitumor activity in HCC . Currently, it represents the only approved therapy for advanced HCC .…”

Multiple Roles of Autophagy in the Sorafenib Resistance of Hepatocellular Carcinoma

“…Sorafenib (BAY 43-9006, Nexavar®), an oral multikinase inhibitor, remains the only FDA-approved systemic drug for patients with advanced HCC [8-10]. Sorafenib was approved for the treatment of patients with advanced HCC on the basis of two international randomized, controlled trials (RCTs), the SHARP (Sorafenib HCC Assessment Randomized Protocol) and the Asia-Pacific trials [11, 12].…”

Sorafenib and a novel immune therapy in lung metastasis from hepatocellular carcinoma following hepatectomy: A case report

“…However, a considerable proportion of patients may develop HCC recurrence and the survival of such patients is very poor, as recurrent tumors are usually aggressive and unresectable (3). Moreover, HCC is significantly resistant to radio-or chemotherapy, the standard of care in the majority of advanced tumors (2).…”

“…Curative resection or liver transplantation is recommended for early-stage HCC, with a reported 5-year survival of >50% (2). However, a considerable proportion of patients may develop HCC recurrence and the survival of such patients is very poor, as recurrent tumors are usually aggressive and unresectable (3).…”