Sorafenib for the treatment of advanced hepatocellular carcinoma with extrahepatic metastasis: a prospective multicenter cohort study

Abstract

Sorafenib, an oral multikinase inhibitor, is approved for advanced hepatocellular carcinoma (HCC) treatment. However, its therapeutic effect in advanced HCC patients with extrahepatic metastasis remains uncertain. This study aimed to prospectively assess the efficacy, safety, and survival risk factors and evaluate the prognostic impact of sorafenib treatment in advanced HCC patients with or without extrahepatic metastasis. Between May 2009 and March 2014, 312 consecutive advanced HCC patients who received sorafenib were enrolled in this study. We evaluated their characteristics and compared the clinical outcomes of those with and without extrahepatic metastasis. Of the enrolled patients, 245 (81%) received sorafenib treatment for more than 1 month, with a median duration of 3.6 months. Eighteen patients demonstrated partial response to sorafenib therapy, 127 had stable disease, and 134 had progressive disease at the first radiologic assessment. The median survival time (MST) and progression‐free survival (PFS) were 10.3 and 3.6 months, respectively. Multivariate analysis identified gender, Child‐Pugh class, baseline serum des‐gamma‐carboxy prothrombin level, and treatment duration as independent risk factors for survival. Extrahepatic metastasis was detected in 178 patients. However, the MST, PFS, and therapeutic effect were comparable between patients with and without extrahepatic metastasis. The independent risk factors for decreased overall survival in patients with extrahepatic metastasis were similar to those affecting all patients. Our results indicated that sorafenib could be administered for hepatic reserve and as long‐term treatment for advanced HCC patients regardless of their extrahepatic metastasis status.

Dose and Location of Irradiation Determine Survival for Patients with Hepatocellular Carcinoma with Macrovascular Invasion in External Beam Radiation Therapy

“…Aino et al[32] have reported that local control of hepatic lesions contribute to better survival benefits, even for the patients with EHM. According to the report by Nakano et al[33, 34], advanced hepatic lesions, such as MVI, strongly correlate with poor survival and RR for treatments like sorafenib, which suggests that we need to develop an optimal multidisciplinary therapeutic strategy for advanced HCC to control local hepatic lesions. In this study, maximal RR and DCR of EBRT for MVI tumor thrombus were 55 and 85%, respectively, which suggests that the ability of local control of EBRT is extremely high.…”

Role of DUSP1/MKP1 in tumorigenesis, tumor progression and therapy

“…Sorafenib is an effective and widely used molecular target drug in HCC [53][54][55][56][57]. Besides the classical pathway directly targeting HCC, sorafenib was found to mediate the antitumor effect via macrophages.…”

“…Trastuzumab decreased DUSP1 which leads to the accumulation of phosphorylated active forms of JNK to enhance apoptotic induction. However, DUSP1 was somehow found to be increased in anti-HER2 therapyresistant cells and combined approaches interrupting both HER2 signaling and DUSP1 activity have proven even more successful [57].…”

Clinical effects and safety of intra‑arterial infusion therapy of cisplatin suspension in lipiodol combined with 5‑fluorouracil versus sorafenib, for advanced hepatocellular carcinoma with macroscopic vascular invasion without extra‑hepatic spread: A prospective cohort study

“…The landscape of systemic therapy for advanced HCC has changed with the advent of molecular-targeted therapy. Sorafenib, a relatively new molecular-targeted therapy for advanced HCC, was approved in Japan in May 2009 (11)(12)(13). Sorafenib is a multi-kinase inhibitor targeting the vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and proto-oncoprotein c-Raf, among others (14,15).…”