S-1 plus sorafenib for the treatment of advanced hepatocellular carcinoma.

PURPOSE: To assess the efficacy and safety of S-1 plus sorafenib for the treatment of advanced hepatocellular carcinoma (HCC). METHODS: PubMed, the Cochrane Library, EMBASE, and ClinicalTrials.gov were searched using the terms "Hepatocellular Carcinoma" or "HCC" or "Hepatoma" or "Liver cancer" and "S-1" and "Sorafenib" or "Nexavar". Outcomes of main interest included overall survival (OS) and toxicities. RESULTS: We identified 2 studies of S"1 plus sorafenib from 77 references that included a total of 65 patients. The percentage of male patients ranged from 70.0 to 89.5%. Median age was 59.2 years and ranged from 48.0 to 65.5 years. The percentage of hepatitis B virus ranged from 23.1 to 90.0%. The recommended dose of S-1 and sorafenib was 80 or 64 mg/m2/day and 800 mg/day, respectively and treatment was administered orally on days 1-14 and days 1-21, respectively. Median OS were 10.4 and 10.5 months, respectively. The incidence of all-grade toxicities of more than 30% were hand"foot syndrome (HFS) and rash. The incidence of grade 3/4 toxicities more than 5% were thrombocytopenia, elevated AST/ALT and hyperbilirubinemia. CONCLUSION: This systematic review suggests that S-1 plus sorafenib showed modest clinical efficacy and tolerable toxicity profile in patients with advanced HCC. The recommended dose of S-1 and sorafenib was 80 or 64 mg/m2/day and 800 mg/day, respectively.

Metronomic S-1 chemotherapy plus transcatheter arterial chemoembolization (TACE): a promising treatment of hepatocellular carcinoma refractory to TACE.

PURPOSE: To assess the efficacy and safety of metronomic S-1 chemotherapy combination with transcatheter arterial chemoembolization (TACE) for the treatment of Barcelona Clinic Liver Cancer (BCLC) Stage B hepatocellular carcinoma (HCC) refractory to TACE. METHODS: Twenty six patients met the eligibility criteria and were enrolled. TACE was performed on day 1, and metronomic S-1 chemotherapy on days 2-15. Tumor assessment was performed one month later. The primary endpoints were time to progression (TTP) and adverse events (AE). RESULTS: Twenty six patients in total received 176 TACE interventions. There were 101 TACE interventions in 15 patients of metronomic S-1 chemotherapy plus TACE (TS) and 75 in 11 patients of TACE monotherapy (TM). Fifteen TS patients received a total of 55 cycles of treatment with S-1, with a median of 4 cycles (range 2-6). The total dose of S-1 was 6165 mg per day in 15 patients (average 120 mg, range 100-125). Median TTP and overall survival (OS) of TS group were 6 months (95% CI, 4.7-7.3) and 17 months (95% CI, 15.6-18.4), respectively, while for the TM group were 4 months (95% CI, 2.4-5.6) and 15 months (95% CI, 9.2-20.8), respectively. Though there were higher tumor response rate (RR) and disease control rates (DCRs) in patients with TS, no significant differences were detected. Both treatment approaches were tolerable with low grade AE. CONCLUSIONS: In the present study, metronomic S-1 chemotherapy plus TACE in the present study was tolerable and associated with a better but not statistically significant TTP, RR and OS. It showed that metronomic S-1 chemotherapy plus TACE may be a promising treatment of BCLC Stage B HCC refractory to TACE.