Systemic therapy of hepatocellular carcinoma: Are we making progress?

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer deaths. Surgical resection, with or without transplantation, can result in long-term survival. However, surgery can only be performed in about 15% of patients with HCC and the 5-year survival rate is only approximately 33%-50% after potentially curative resection. Percutaneous ethanol injection, radiofrequency ablation, and transarterial chemoembolization are invasive techniques that have shown efficacy in reducing tumor bulk. Similarly, systemic chemotherapy may induce tumor responses, but a survival benefit has not been clearly demonstrated. In addition, the lack of efficacy of antiandrogens, tamoxifen, and single-agent interferon has now been confirmed.Sorafenib is a multikinase inhibitor with antiangiogenic, proapoptotic, and Raf kinase inhibitory activity. In a large, multicenter, randomized, phase 3 trial there was a significant improvement in both time to disease progression and overall survival with sorafenib compared with placebo. Sorafenib is the first agent to demonstrate a consistent improvement in overall survival for patients with advanced HCC. Further studies are required to determine the role of other molecular-targeted therapies, either alone or in combination with sorafenib in patients with advanced HCC. Further studies are also required to determine the role of sorafenib in combination with locoregional therapies (eg, transarterial chemoembolization), and the role of sorafenib as adjuvant therapy following surgery.

Development of Molecularly Targeted Therapies in Hepatocellular Carcinoma: Where Do We Go Now?

“…Unfortunately, most HCC patients present with disease, making them ineligible for curative therapies such as surgical resection or liver transplantation (4). Only 15% of patients are eligible for surgical management involving hepatic resection or transplantation (5). Five-year survival rates of >70% can be achieved in these patients, but recurrences are inevitable.…”

Intravenous liposomal delivery of the short hairpin RNAs against Plk1 controls the growth of established human hepatocellular carcinoma

“…Despite significant advances made during the past several decades for the treatment of hepatocellular carcinoma, the overall 5 year survival rate remains poor. 3 Therefore, identification of new therapeutic targets and treatment strategies is essential for successful control of the development and progress of hepatocellular carcinoma.…”

Optimal management of hepatocellular carcinoma: Challenges and opportunities

“…4 Other risk factors for HCC, some of which also vary by geography, include other causes of cirrhosis, such as heavy alcohol consumption and hemochromatosis. 7,8 Therapeutic options are available for HCC, including liver transplantation, surgical resection and percutaneous ablation techniques, and these can be potentially 'curative' if HCC is diagnosed at an early stage. Use of these options varies between Asian and Western countries, 7 but they are generally restricted to patients with early-stage HCC without advanced cirrhosis.…”

“…Use of these options varies between Asian and Western countries, 7 but they are generally restricted to patients with early-stage HCC without advanced cirrhosis. 7,8 Most HCC patients present with advanced disease and are ineligible for 'curative' interventions. 7 For patients who have unresectable and intermediate-stage HCC, transarterial chemoembolization (TACE) is the most commonly adopted therapy.…”

“…5,6 Although endoscopic resection is safer than surgery, it still carries the risk of early complications like bleeding (2-15%), perforation (0-4%), cholangitis (0-2%) and acute pancreatitis (8-15%), as well as late complications like papillary stenosis (0-8%). 7,8 Researchers are constantly striving to develop technology and techniques to prevent, minimize or effectively handle these complications. 9 A number of studies have focused on preventing post-procedure acute pancreatitis.…”