Yau Thomas, Chan Pierre, Epstein Richard, Poon Ronnie Tung Ping
University Department of Medicine, Queen Mary Hospital, Hong Kong, Hong Kong.
Liver Int. 2009 Jan;29(1):10-7. doi: 10.1111/j.1478-3231.2008.01916.x.
Systemic chemotherapy has had a disappointing track record in the management of advanced hepatocellular carcinoma (HCC). Single-agent doxorubicin produces a response rate of 10-15%, but without any survival benefit, and combination chemotherapy has also yielded unimpressive results. With recent advances in the knowledge of hepato-carcinogenesis, there has been encouraging development in the systemic therapy of advanced HCC patients, and particularly in the targeted therapy of advanced HCC. Among the newly identified targets, exciting results have been shown in targeting the anti-angiogenic pathway and the Raf/mitogen-activated protein kinase pathways. Bevacizumab, both as a single agent and in combination with other agents, has shown initial encouraging activity in treating advanced HCC. More recently, single-agent sorafenib, a putative multitargeted kinase inhibitor, has shown to prolong the overall survival of patients with advanced HCC in the pivotal phase III Sorafenib HCC Assessment Randomized Protocol (SHARP) and Oriental study. Currently, sorafenib is the only approved targeted therapy for patients with advanced HCC. In addition, however, promising early results have been reported for other molecular-targeted drugs including erlotinib and sunitinib. Future progress seems likely to depend on using controlled clinical trials to optimize synergistic combination treatments.
全身化疗在晚期肝细胞癌（HCC）的治疗中有着令人失望的记录。单药阿霉素的缓解率为10%-15%，但无生存获益，联合化疗的结果也不尽人意。随着肝癌发生机制研究的最新进展，晚期HCC患者的全身治疗，尤其是晚期HCC的靶向治疗取得了令人鼓舞的进展。在新发现的靶点中，针对抗血管生成途径和Raf/丝裂原活化蛋白激酶途径的治疗已显示出令人兴奋的结果。贝伐单抗单药及与其他药物联合应用，在治疗晚期HCC方面已显示出初步的鼓舞人心的活性。最近，在关键的III期索拉非尼肝癌评估随机方案（SHARP）和东方研究中，单药索拉非尼（一种假定的多靶点激酶抑制剂）已显示可延长晚期HCC患者的总生存期。目前，索拉非尼是唯一被批准用于晚期HCC患者的靶向治疗药物。然而，此外，包括厄洛替尼和舒尼替尼在内的其他分子靶向药物也已报告了有前景的早期结果。未来的进展可能取决于使用对照临床试验来优化协同联合治疗。
