Transcatheter hepatic arterial chemoembolization plus cinobufotalin injection adjuvant therapy for advanced hepatocellular carcinoma: a meta-analysis of 27 trials involving 2,079 patients

Objective: The aim of this study was to systematically investigate the safety and efficacy of the combination of transcatheter hepatic arterial chemoembolization (TACE) and cinobufotalin injection for advanced hepatocellular carcinoma (HC). Methods: Clinical trials were searched from Web of Science, Cochrane Library, PubMed, Embase, Chinese Medical Citation Index (CMCI), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), and Wanfang database. Outcome measures including therapeutic efficacy, quality of life, liver function, immune function, and adverse events were extracted and evaluated. Results: After final assessment, 27 studies including 2,079 advanced HC patients were involved in this study. Compared with TACE alone, the combination of TACE with cinobufotalin injection adjuvant therapy significantly prolonged the patients' 1-, 1.5-, 2-, and 3-year overall survival (OS) rate (1-year OS, OR=2.84, 95% CI=2.20-3.67, P<0.00001; 1.5- year OS, OR=3.57, 95% CI=1.92-6.66, P<0.0001; 2-year OS, OR=3.17, 95% CI=2.36-4.25, P<0.00001; 3-year OS, OR=2.88, 95% CI=1.82-4.57, P<0.00001). The combined therapy also improved patients' overall response rate (ORR; OR=1.86, 95% CI=1.54-2.24, P<0.00001), disease control rate (DCR; OR=2.05, 95% CI=1.59-2.64, P<0.00001), and quality of life improved rate (QIR; OR=3.45, 95% CI=2.52-4.72, P<0.00001). Moreover, the immune function and liver function of HC patients were all significantly enhanced after the combined therapy of TACE and cinobufotalin injection (CD3(+), P=0.001; CD4(+), P=0.0006; CD4(+)/CD8(+), P=0.03; natural killer [NK] cell, P=0.01; total bilirubin [TBIL], P=0.003; alanine aminotransferase [ALT], P<0.00001; aspartate aminotransferase [AST], P<0.00001). No serious adverse events occurred during cinobufotalin injection-mediated therapy. Conclusion: The combination of TACE and cinobufotalin injection adjuvant therapy is safe and more effective for end-stage HC treatment than TACE alone.