Thalidomide Combined with Transcatheter Arterial Chemoembolization (TACE) for Intermediate or Advanced Hepatocellular Carcinoma: a Systematic Review and GRADE Approach

Abstract

Objective:According to current guidelines, there is no clear second-line treatment for advanced liver cancer.<br />In practice, clinicians have attempted to use thalidomide(TLD) combined with transcatheter arterial chemoembolization<br />(TACE) for treating liver cancer. This study aims to assess the clinical efficacy and safety of TLD combined with TACE<br />in patients with intermediate or advanced hepatocellular carcinoma. Methods: Medline, Embase, the Cochrane Central<br />Register of Controlled Trials (CENTRAL), database of ClinicalTrials.gov, CBM, CNKI, VIP and Wanfang database<br />were searched for eligible studies. Criteria for inclusion in our meta-analysis included a study that patients diagnosed<br />with intermediate or advanced HCC, the use of TACE plus TLD or its derivatives, and the availability of outcome<br />data for survival. A meta-analysis was conducted to summarize the evidences of randomized controlled trials (RCTs).<br />And finally, the GRADE approach was used to assess the quality of these evidences. Results: Twelve RCTs involving<br />894 Hepatocellular Carcinoma (HCC) patients were included. The meta-analysis results showed that TACE plus TLD was<br />significantly superior than TACE alone in terms of 12-month survival rate (OR=2.55, 95% CI:1.78-3.64, P<0.01), 24-month<br />survival rate (OR=2.95, 95% CI:1.96-4.44, P<0.01), 36-month survival rate (OR=2.95, 95% CI:1.41-6.19, P<0.004),<br />progression-free survival (PFS) (MD=2.23, 95% CI:1.19-3.28 , P<0.001), objective response rate (OR=1.84, 95%<br />CI:1.34-2.52, P<0.0001), and disease control rate (OR=2.68, 95% CI:1.80-3.99). Subgroup analysis demonstrated<br />no differences across related outcomes. Sensitivity analyses showed no important differences in the estimates of<br />effects. Quality of evidence for all outcomes was rated moderate to very low after applying GRADE approach.<br />Conclusions: Current evidence seemed to support the suggestion that TACE plus TLD as the second line treatment for<br />patients with intermediate or advanced HCC. However, this finding is not definitive due to the poor quality of included<br />studies, more carefully designed and conducted RCTs are warranted to confirm above conclusions.