Prospective Observational Study of Sorafenib in Hepatocellular Carcinoma Patients With Very High Risk of Recurrence After Surgery

Background/Aim: Surgical resection remains the mainstay of treatment for hepatocellular carcinoma (HCC). However, reducing the risk of postoperative recurrence is urgently needed. We planned a prospective observational study to investigate the efficacy and safety of adding sorafenib in a maintenance setting after surgery in HCC patients with high risk of recurrence. Patients and Methods: Patients with HCC (invasion of the hepatic vein or inferior vena cava or tumor size >7 cm or tumor to nontumor standardized uptake value ratio >2 by fluorodeoxyglucose positron emission tomography) who underwent macroscopically curative resection were eligible. Dose and schedule of sorafenib were set at 800 mg/day for six months after hepatic resection. The primary endpoint was progression-free survival, and the secondary endpoints were overall survival and safety. This study was registered with the UMIN Clinical Trials Registry (UMIN000013089). Results: Ten patients were evaluated. Six patients completed the pre-planned treatment. Three patients discontinued treatment because of disease progression (lung metastasis in two patients and liver metastasis in one), and one patient discontinued because of pneumonia. The most common drug-related adverse event was increased γ-glutamyl transpeptidase (γGTP). None of the patients suffered grade 4 adverse events. The median progression-free survival was 380 (range=38-1,555) days. The median overall survival was 1000 (range=850-1,705) days. Four patients survived without disease progression for more than 800 days. Conclusion: Although the sample size was limited, this is the first study to demonstrate the safety and efficacy of sorafenib in a maintenance setting after surgery for HCC patients with high risk of recurrence.