Thalidomide Combined with Transcatheter Arterial Chemoembolization (TACE) for Intermediate or Advanced Hepatocellular Carcinoma: A Systematic Review and GR

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