Abstract

Background Combination therapy of transarterial chemoembolization plus sorafenib (TACE-S) has been proven to be safe and effective for hepatocellular carcinoma (HCC); however, this combination therapy is associated with a high incidence of adverse events (AEs). Our study focused on the relationships between AEs and treatment outcomes and aimed to discover AE-based clinical markers that can predict the survival benefits of combination treatment. Methods From January 2010 to June 2014, a total of 235 HCC patients treated with TACE-S were retrospectively enrolled. Major sorafenib-related AEs were prospectively recorded, and their correlations with overall survival (OS) were analysed using time-dependent covariate Cox regression analyses. Results The majority of the patients (200, 85.1%) were male, and the median age was 51 years old. After two years of follow-up, the median OS of the study population reached 12.4 months. In all, 218 patients (92.8%) presented at least one AE, and 174 (74.0%) suffered AEs ≥2 grade. Based on time-dependent multivariate analyses, the development of hand-foot skin reaction (HFSR) ≥2 grade (HR = 0.43, 95% CI: 0.32–0.58, P < 0.001) and diarrhoea ≥1 grade (HR = 0.72, 95% CI: 0.53–0.97, P=0.029) were identified as independent predictors of prolonged OS. Moreover, patients who developed both HFSR ≥2 grade and diarrhoea ≥1 grade achieved better outcomes than those patients who developed either or neither of these AEs (HR = 1.51, 95% CI: 1.11–2.06, P=0.009). Conclusions The development of HFSR ≥2 grade or diarrhoea ≥1 grade during TACE-S treatment indicated prolonged OS, and these AEs should be considered important clinical markers for predicting patient prognoses.

Highlights

  • Combination therapy of transarterial chemoembolization plus sorafenib (TACE-S) has been proven to be safe and effective for hepatocellular carcinoma (HCC); this combination therapy is associated with a high incidence of adverse events (AEs)

  • Sorafenib was administered with a median duration of 12.5 (IQR 7.8–22.7) months. e median cycle of TACE was 3 (IQR 1–4). e median overall survival (OS) was 12.4 months

  • As early as 2004, when Perez-Soler et al applied erlotinib treatment for non-small-cell lung cancer (NSCLC), these authors found that the occurrence and severity of rash were associated with survival improvement [4]

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Summary

Introduction

Combination therapy of transarterial chemoembolization plus sorafenib (TACE-S) has been proven to be safe and effective for hepatocellular carcinoma (HCC); this combination therapy is associated with a high incidence of adverse events (AEs). Hepatocellular carcinoma (HCC), the third leading cause of cancer and the fifth most common malignant tumour, results in 700,000 patient deaths worldwide every year [1]. Liver transplantation, radiofrequency ablation, transarterial chemoembolization (TACE) and sorafenib are major therapies for treating HCC across different Barcelona Clinic Liver Cancer (BCLC) stages. While TACE is the recommended therapy for BCLC-B HCC, sorafenib is the standard targeted treatment for advanced disease [2]. Combination therapy of TACE plus sorafenib (TACE-S) has been investigated in many studies and is an attractive treatment for decreasing the upregulation of VEGF. The safety of TACE-S has already been proven, its superiority over TACE alone remains controversial

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