Epirubicin, Cisplatin, 5-FU combination chemotherapy in sorafenib-refractory metastatic hepatocellular carcinoma

Table 1 Patients’ general characteristics n (%)

	Numbers
Age (range), yr	531 (36-71)
Sex
Male	25 (81)
Female	6 (19)
Etiology
HBV	26 (83.9)
HCV	1 (3.2)
Others	4 (12.9)
Status of primary liver mass
Stable	13 (41.9)
Progressive	18 (58.1)
Metastatic sites
Lung	28 (90.3)
Lymph node	10 (32.3)
Bone	8 (25.1)
Peritoneum	3 (9.7)
Previous treatment before sorafenib
TACE	29 (93.5)
Surgery	17 (54.8)
Radiation	12 (38.7)
Hepatic arterial infusion	9 (29.0)
Radiofrequency ablation	5 (16.1)

¹Median. TACE: Transarterial chemoembolization; HBV: Hepatitis B virus; HCV: Hepatitis C virus.

Table 2 Clinical outcomes

Response	n(%)
PR	4 (12.9)
SD	10 (32.3)
Disease control (PR + SD)	14 (45.2)
Progressive disease	17 (54.8)
Survival outcome	median (range)
Median TTP	2.7 mo (1.0-14.8)
Median OS	7.8 mo (2.2-40.2)

PR: Partial response, 30% or more decrease in the sum of diameters of target lesions; SD: Stable disease, neither sufficient shrinkage to qualify as PR nor sufficient to qualify as disease progression; TTP: Time to progression; OS: Overall survival; PD: Progressive disease.

Table 3 Analysis of prognostic factors

Characteristics	OS		TTP
	HR	P value	HR	P value
Univariate analysis
Gender
Male vs female	0.870	0.804	0.87	0.793
Age, yr
< 60 vs≥ 60	0.090	0.023	0.46	0.143
Primary liver mass control
Yes vs no	4.220	0.006	3.56	0.006
Disease control
PR + SD vs PD	5.960	< 0.001	45.3	< 0.001
Multivariate analysis
Age, yr
< 60 vs≥ 60	0.074	0.017	0.91	0.800
Primary liver mass control
Yes vs no	3.660	0.026	1.38	0.540
Disease control
PR + SD vs PD	4.310	0.011	36.69	0.001

In univariate and multivariate analysis, patients with age over than 60 or stable primary liver mass showed the better OS and TTP. The patients with partial response or stable disease also had better survival outcome but not in time to progression in multivariate analysis. PR: Partial response; PD: Progressive disease. OS: Overall survival: TTP: Time to progression.

Table 4 Toxicity profiles n (%)

	Grade 1/2	Grade 3/4	Total
Hematologic
Anemia	72 (70.6)	10 (9.8)	82 (80.4)
Neutropenia	15 (14.7)	55 (53.9)	70 (68.6)
Thrombocytopenia	61 (59.8)	28 (27.4)	89 (87.2)
Non-Hematologic
Nausea	4 (3.9)	0	4 (3.9)
Vomiting	2 (1.9)	0	2 (1.9)
Asthenia	24 (23.5)	3 (2.9)	27 (26.4)
Anorexia	2 (1.9)	0	2 (1.9)
Microsites	6 (5.8)	0	6 (5.8)

Number: Each episodes of all cycles/Percent: Number of episode/total 102 cycles.