High cholinesterase predicts tolerance to sorafenib treatment and improved prognosis in patients with transarterial chemoembolization refractory intermediate stage hepatocellular carcinoma

Shintaro Takaki; Takayuki Fukuhara; Nami Mori; Keiji Tsuji

doi:10.3892/mco.2019.1949

High cholinesterase predicts tolerance to sorafenib treatment and improved prognosis in patients with transarterial chemoembolization refractory intermediate stage hepatocellular carcinoma

Mol Clin Oncol. 2020 Jan;12(1):60-68. doi: 10.3892/mco.2019.1949. Epub 2019 Nov 18.

Authors

Shintaro Takaki¹, Takayuki Fukuhara¹, Nami Mori¹, Keiji Tsuji¹

Affiliation

¹ Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima 730-8619, Japan.

Abstract

Although sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC), the predictive factors sorafenib tolerance in intermediate-stage HCC cannot be accurately determined. The aim of the current study was to identify the predictive characteristics for the continuation of sorafenib treatment (≥400 mg) in patients with transarterial chemoembolization (TACE)-refractory intermediate HCC and to identify candidates for second-line sorafenib treatment. A total of 33 TACE-refractory intermediate patients with HCC that were treated with sorafenib, and who had reached progressive disease (PD), were analyzed in the present retrospective study. Of 33 patients, 6 patients (18.1%) were able to continue sorafenib treatment (≥400 mg) until PD, however, a total of 27 patients (71.9%) were unable to continue treatment (<400 mg). The current study compared the baseline characteristics parameters to sorafenib ≥400 mg and <400 mg using a logistic regression model. The overall survival (OS) of patients receiving sorafenib ≥400 mg treatment was significantly increased compared with patients receiving sorafenib treatment <400 mg [554.5 days (228-674) vs. 219 days (134-369); P=0.0315). A univariate analysis was performed and indicated that Age (<75 years; P=0.021), total cholesterol (>180 mg/dl; P=0.026) and cholinesterase (ChE; ≥220 U/l; P=0.024) were significant factors, and a multivariate analysis indicated that ChE (≥220 U/l) was a significant prognostic factor (HR: 11.9; 95% CI: 1.19-118.0; P=0.004). Both progression-free survival [279 (204-403) vs. 117.5 (63-197) days; P=0.0136] and OS [470 (277-679) vs. 171.5 (80-236) days; P=0.0004] were significantly increased in patients with ChE levels ≥220 U/l compared with patients exhibiting ChE levels <220 U/l. Baseline high value of ChE in intermediate-stage HCC predicts the ability to continue sorafenib treatment at ≥400 mg.

Keywords: hepatocellular carcinoma; intermediate; second-line; sorafenib; transarterial chemoembolization refractory.