Initial and maintenance dose of sorafenib in female patients with advanced hepatocellular carcinoma should be modified to maximize therapeutic effect.

Abstract

497 Background: Sorafenib is the only approved first-line agent in patients with advanced HCC and patients who showed progressive disease after sorafenib therapy have an opportunity to receive regorafeib as 2nd-line agent. Therefore, it is very important to maintain sorafenib therapy until sorafenib resistance occurs. We retrospectively analyzed initial and maintenance dose especially in female patients. Methods: A total of 232 patients with advanced HCC who received sorafenib in our institution from July, 2009 until May, 2017 were enrolled. Overall survival (OS), radiological response evaluated by modified RECIST criteria and dose of sorafenib were analyzed. Results: The 232 patients included 179 males and 53 females, with a mean age of 71 ± 9 years. The majority of patients (N = 131, 56.4%) were HCV Ab positive and HBs Ag was positive in 29 patients. Eighty-six patients had extrahepatic metastasis and 50 patients showed major portal invasion defined as VP3 or VP4 by Liver Cancer Study Group of Japan. The overall survival rates of the 232 patients at 6, 12 and 18 were 72.4%, 53.6% and 41.9%, and MST was 14 months. In all patients no existence of major portal invasion, serum Albumin level ≧3.5g/dl before administration of sorafenib, and post-sorafenib anticancer therapy were independently associated with OS. The mean age of female patients was 75 years and mean body weight was 49kg. In female patients only 5 patients (9.4%) showed over 60kg. The dose reduction of sorafenib was necessary in all female patients and 26 female patients could receive post-sorafenib anticancer therapy including regorafenib. The muscle mass calculated by direct segmental multifrequency bioelectrical impedance analysis method was associated with duration of sorafenib therapy, dose reduction of sorafenib and possibility of post-sorafenib anticancer therapy. Conclusions: The modification of sorafenib dose according to sex and muscle mass is clinically important to improve overall survival in patients with advanced HCC treated with sorafenib. It is associated with duration of sorafenib therapy and the possibility for induction of other therapies after sorafenib failure.