Changes in plasma interleukin-8 and tumor necrosis factor-α levels during the early treatment period as a predictor of the response to sorafenib in patients with unresectable hepatocellular carcinoma

Abstract

Purpose

This study aimed to identify a biomarker for predicting the response to sorafenib in patients with hepatocellular carcinoma (HCC).

Methods

Of 100 patients with unresectable HCC who received sorafenib treatment in our institute (Cohort A), 48 had stored plasma samples collected within 28 days before the start of treatment (Cohort B). Concentrations of 18 plasma cytokines were measured in plasma samples using a sandwich immunoassay with multiplexed fluorescent bead-based technology. Among 27 patients with follow-up plasma samples taken at 5–10 days of treatment (Cohort C), changes in the 18 cytokines were also evaluated.

Results

In Cohort A, progressive disease (PD) according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) was associated with poor overall survival by multivariate analysis (p = 0.024). In Cohort B, no significant differences in baseline concentrations of α-fetoprotein, des-γ-carboxy prothrombin, or the 18 cytokines were found between patients with PD and those with stable disease (SD) or partial response (PR). In Cohort C, the increase in interleukin-8 and tumor necrosis factor-α (TNF-α) was significant in the PD group (p = 0.0063 and p < 0.001, respectively) but not in the SD + PR group (p = 0.67 and p = 0.15, respectively). In addition, the fold changes in interleukin-8 and in TNF-α were correlated (p < 0.001, r = 0.67).

Conclusions

Changes in plasma interleukin-8 and TNF-α levels during the first few days could predict the response to sorafenib therapy in HCC patients.

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