Table 4. Other combination regimens based on targeted therapy in hepatocellular carcinoma (with published results).

Agents	Stage	Patients(n)	Therapeutic scheme	First or second line	Efficacy (combined therapy vs monotherapy)	Adverse events (AEs)	Ref
Radiofrequency ablation (RFA) + Sorafenib	Phase 2	128	Radiofrequency ablation plus sorafenib (400mg bid) (n = 64) vs radiofrequency ablation alone (n = 64)	Both	mOS: 161.8 vs 118.6 weeks. The 1-, 2- and 3- year cumulative incidences: 62.8%, 85.4% and 92.7% vs 40.5%, 62.9% and 74.5%.	gastrointestinal bleeding, pleural effusion requiring drainage, mild or moderate increase in body temperature.	[87]
Radiofrequency ablation (RFA) + Sorafenib	Phase 2	45	Radiofrequency ablation plus sorafenib (400mg bid) (n = 15) vs radiofrequency ablation alone (n = 30)	Both	RFA-induced ablated area: 46.3 mm ± 10.3 and 33.0 mm ± 6.9 vs 32.9 mm ± 7.6 and 25.6 mm ± 5.7.	serum asparatate aminotransferase concentration transient increases, handfoot skin reaction.	[116]
Radiofrequency ablation (RFA) + Sorafenib	Phase 2	62	Radiofrequency ablation plus sorafenib (400mg bid) (n = 30) vs radiofrequency ablation alone (n = 32)	First line	recurrent rate: 56.7% vs 87.5%; mTTP: 17.0 vs 6.1 months;	hand-foot skin reactions, diarrhea, fatigue, alopecia and hypertension.	[86]